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The study was ended for strategic reasons and changes in the external environment.
The safety profile and risk benefit ratio for PF-0674775 remained unchanged.
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This is a Phase 1/2 study of PF-06747775 as a single agent and in combination with other cancer treatments in patients with advanced EGFRm NSCLC. The overall clinical study consists of a Phase 1 single agent dose-escalation and expansion part to determine the RP2D of PF-06747775 single agent in patients with previously-treated EGFRm NSCLC followed by sequential evaluations of PF-06747775 at the RP2D in 3 different clinical scenarios as detailed below:
There remains an unmet medical need to develop EGFR TKI agents that effectively target both the single activating mutations of del 19 and L858R, and the secondary resistance mutation T790M, while sparing WT EGFR. Drugs active against the resistance mutation will enable molecularly targeted therapy with a more favorable toxicity profile than the current standard of cytotoxic chemotherapy platinum based doublets. Furthermore, by having a wide margin of selectivity favoring the EGFR mutants versus WT EGFR, PF 06747775 is likely to be positioned to improve patient outcomes from an efficacy and safety perspective.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Cohort 1 will be initiated (current dose 200 mg) |
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| Cohort 2A | Experimental | Cohort 2A will evaluate PF-06747775 200 mg by mouth (PO) daily (QD) in combination with palbociclib continuous PO QD dosing in 21-day cycles. The starting dose (DL1) for palbociclib will be 100 mg PO daily. Dose finding will follow mTPI method with adjustments using DLT rate. |
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| Cohort 2B | Experimental | Cohort 2B will be initiated once the RP2D of the PF-06747775 and palbociclib combination is determined. |
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| Cohort 3 | Experimental | Cohort 3 combination is PF-06747775 200 mg PO QD and avelumab 10 mg/kg IV Q2W in 28-day (4-week) cycles. Dose finding will follow the mTPI design. Once RP2D of PF-06747775 in combination with avelumab is determined, the Dose Expansion Phase will be opened. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-06747775 | Drug |
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| Palbociclib |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) During the First Cycle in Phase 1 Dose-escalation Cohorts, Japan LIC and Phase 1b Cohort 3, and First 2 Cycles in Phase 1b Cohort 2A | DLT was defined as any of the following adverse events (AEs) occurring during the first cycle for Phase 1 dose-escalation cohorts, Japan LIC and Phase 1b Cohort 3, or the first 2 cycles for Phase 1b Cohort 2A of treatment, and considered attributable to study intervention: Grade 4 neutropenia >7 days; febrile neutropenia; Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade >=3 non-hematologic toxicities; Grade 4 rash, mucositis, or diarrhea; failure to receive at least 70% of planned doses; Grade 3 QTcF prolongation in asymptomatic participants; treatment-related AEs attributable to PF-06747775, palbociclib or both that caused palbociclib treatment delay >= 10 days or omission of at least 12 doses of the combination. Grade of AE was defined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. | 21 days for Phase 1 dose-escalation cohorts and Japan LIC; 42 days for Phase 1b Cohort 2A; 28 days for Phase 1b Cohort 3 |
| Number of Participants With Confirmed Objective Response (OR) in PF-06747775 200 mg QD Group | Number of participants with confirmed OR according to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. Complete response (CR) was defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. | Baseline up to end of treatment (maximum of 165 weeks) |
| Progression-free Survival (PFS) in Phase 2 Cohort 2B | PFS was based on Kaplan-Meier estimates. PFS was defined as the time from Cycle 1 Day 1 to the date of the first documentation of objective progression (PD) or death due to any cause. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. | Cycle 1 Day 1 up to the end of study (maximum of 5 years) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent AEs (TEAEs) in All Cohorts All Phases (All-causality) | AE = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. Grade 3 (Severe) events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events = death related to an AE. Treatment-emergent events = between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
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Partial Inclusion criteria:
Evidence of histologically or cytologically confirmed diagnosis of locally advanced or metastatic EGFRm (del 19 or L858R) NSCLC:
As detected by local EGFR mutation test that includes QIAGEN therascreen EGFR RGQ PCR kit, Roche cobas® EGFR Mutation Test or a sponsor-approved laboratory developed test that is validated in a CLIA laboratory (with tissue submitted for central laboratory confirmation via FDA approved QIAGEN therascreen RCQ PCR kit).
T790M disease as follows:
Phase 1 If a repeat biopsy was performed on the tumor following prior EGFR TKI therapy, then T790M positive disease must be present. Patients of unknown T790M status following EGFR TKI progression (ie, no post EGFR TKI progression biopsy was performed) are eligible.
In the PK sub-studies involving food/antacid and CYP3A4 effects, patients with EGFRm (del 19 or L858R) with any T790M status are eligible to enroll.
Studies at RP2D Cohort 1: Patients may have de novo T790M mutation, but it is not required. Cohort 2 and Cohort 3: Patients must have EGRFm (del 19 AND T790M or L858R AND T790M) NSCLC tumors as detected by local EGFR mutation test that includes QIAGEN Therascreen EGFR RGQ PCR kit, Roche cobas® EGFR Mutation Test or a sponsor-approved laboratory developed test that is validated in a CLIA laboratory, which will then be retrospectively confirmed by the central validated Thermo Fisher Scientific Oncomine Next Generation Sequencing (NGS) cancer panel test. Patients will also be enrolled if they solely test positive for EGFR (del 19 AND T790M or L858R AND T790M) NSCLC in plasma detected by local EGFR mutation test that includes QIAGEN Therascreen EGFR Plasma RGQ kit, Roche cobas® EGFR mutation test v2 (US-IVD) or Sysmex Inostic's OncoBEAMTM EGFR test or a sponsor-approved laboratory developed test that is validated in a CLIA laboratory, which will then be retrospectively confirmed by a validated cfDNA test as determined by the Sponsor.
Prior treatment for EGFRm NSCLC as follows:
Phase 1 Has progressed after at least 1 prior line of therapy including and EGFR TKI. Patients may have also received other lines of therapy before or after the EGFR TKI.
Studies at RP2D Cohort 1: no prior treatment for locally advanced or metastatic EGFRm NSCLC. Cohorts 2 and 3: must have had disease progression on treatment with an approved 1st or 2nd generation EGFR TKI. Patients who have been treated with a 3rd generation EGFR TKI are ineligible for this study. Patients may have had multiple lines of therapy; however, the last therapy prior to study treatment must have been an approved EGFR TKI and received within 6 weeks prior to study registration.
Patients must have at least one measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated.
Tumor tissue available. Requesting formalin fixed paraffin embedded (FFPE) block or 15 unstained sections (5 micron). If a lesser amount of tissue is available, contact the sponsor. An archival specimen is acceptable for Phase 1; a de novo specimen is required for Cohorts 2, and 3 if the T790M status was confirmed by tissue biopsy.
Partial Exclusion Criteria:
For All Phases/Cohorts Previously diagnosed brain metastases, unless the patient has completed the treatment that is clinically indicated, if any, and has recovered from the acute effects of any treatment that was delivered prior to study registration, have discontinued corticosteroid treatment for these metastases prior to registration, and are neurologically stable.
Major surgery within 2 weeks prior to registration.
Radiation therapy, excluding stereotactic radiosurgery (SRS), within 1 week prior to registration.
Systemic anti cancer therapy within 2 weeks or 5 half-lives (whichever is longer) of registration excluding EGFR TKIs. Patients on EGFR TKIs must discontinue the agent for a minimum of:
Partial Exclusions for Cohort 2A and 2B (Palbociclib combo):
Prior treatment with a CDK 4/6 inhibitor.
Partial Exclusions for Cohort 3 (Avelumab combo):
Prior therapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab, tremelimumab or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways).
Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
Use of immunosuppressive medication at time of randomization
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC San Diego Medical Center - La Jolla | La Jolla | California | 92037 | United States | ||
| UC San Diego Moores Cancer Center |
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| Label | URL |
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| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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A total of 65 participants were enrolled, assigned to study treatment and treated in the study. The study was prematurely terminated by sponsor due to an internal strategic decision and changes in the external environment. No safety concerns were related to the study termination. No enrollments occurred in Phase 1 Food Effect and Rifampin Drug-Drug Interaction (DDI) sub-study, Phase 2 Cohort 2B or Phase 1b Cohort 3 prior to study termination.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1 Dose-escalation: PF-06747775 25 mg QD | Participants received a single oral dose of PF-06747775 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 25 mg once daily (QD) for 21-day cycles (up to a maximum of 95 weeks). |
| FG001 | Phase 1 Dose-escalation: PF-06747775 50 mg QD |
| Title | Milestones | Reasons Not Completed | |||||
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| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
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| Prot | Yes | No | No | Study Protocol | Dec 19, 2016 | May 13, 2021 |
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| Drug |
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| Avelumab | Drug |
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| Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks) |
| Number of Participants With TEAEs in All Cohorts All Phases (Treatment-related) | Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Grade 3 (Severe) events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events = death related to an AE. Treatment-emergent events = between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Treatment-related AEs were determined by the investigator. | Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks) |
| Number of Participants With Serious Adverse Events (SAEs) in All Cohorts All Phases | An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-related SAEs were determined by the investigator. | Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks) |
| Number of Participants With Shifts of Laboratory Results From Grade <=2 at Baseline to Grade 3 or 4 Post-baseline in All Cohorts All Phases | Laboratory values included hemoglobin, platelets, white blood cell count (WBC), absolute (abs) neutrophils, abs lymphocytes, abs monocytes, abs eosinophils, abs basophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (Alk Phos), sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose, albumin, phosphorous or phosphate, prothrombin time (PT) or international normalized ratio (INR), partial thromboplastin time (PTT), urinalysis and pregnancy test. Grades of laboratory results were defined by NCI CTCAE version 4.03. Grade 3 (Severe) events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. | Baseline up to the end of treatment (maximum of 195 weeks) |
| Number of Participants Meeting Categorical Criteria of QTcF Values When PF-06747775 Was Given as a Single Agent, and in Combination With Palbociclib and Avelumab. | Number of participants meeting categorical criteria of QTcF values when PF-06747775 was given as a single agent in Phase 1 dose-escalation cohorts, PF-06747775 200 mg QD group (only participants in Phase 2 Cohort 1 and Japan LIC were eligible for QTcF within this combined group), and in combination with palbociclib and avelumab in Phase 1b/2 Cohorts 2A, 2B and 3. Criteria for categorization of QTcF were defined as: maximum values 450 - <480 msec, 480 - <500 msec and >=500 msec. | Baseline up to Cycle 4 Day 1 (maximum of 10 weeks) |
| Number of Participants Meeting Categorical Criteria of QTcB Values When PF-06747775 Was Given as a Single Agent, and in Combination With Palbociclib and Avelumab. | Number of participants meeting categorical criteria of QTcB values when PF-06747775 was given as a single agent in Phase 1 dose-escalation cohorts, PF-06747775 200 mg QD group (only participants in Phase 2 Cohort 1 and Japan LIC were eligible for QTcB within this combined group), and in combination with palbociclib and avelumab in Phase 1b/2 Cohorts 2A, 2B and 3. Criteria for categorization of QTcB were defined as: maximum values 450 - <480 msec, 480 - <500 msec and >=500 msec. | Baseline up to Cycle 4 Day 1 (maximum of 10 weeks) |
| Number of Participants With Confirmed and Unconfirmed OR in Phase 1 Cohorts | Number of participants in Phase 1 cohorts with confirmed and unconfirmed OR according to RECIST v1.1. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable was defined as not qualifying for CR, PR or PD. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. Indeterminate was defined as progression not documented. | Baseline up to end of treatment (maximum of 195 weeks) |
| Objective Response Rate (ORR) in Phase 1b/2 Cohorts 2A, 2B and 3 | ORR was defined as percentage of participants with OR based assessment of CR or PR according to RECIST v1.1 that must have been confirmed ≥4 weeks later. Participants who did not have an on treatment radiographic tumor assessment due to early progression, who received anti tumor treatment other than the study medication prior to reaching a CR or PR, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR were counted as non responders in the assessment of ORR. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. | Baseline up to end of treatment (maximum of 108 weeks) |
| PFS in PF-06747775 200 mg QD Group, Phase 1b Cohorts 2A and 3 | PFS was based on Kaplan-Meier estimates. PFS was defined as the time from Cycle 1 Day 1 to the date of the first documentation of PD or death due to any cause. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. | Cycle 1 Day 1 up to the end of study (maximum of 5 years) |
| Duration of Objective Response (DOR) in Phase 1b/2 Cohorts | DOR was the time from the date of first documentation of confirmed CR or PR to the date of first documentation of PD or death due to any cause. If tumor progression data included more than 1 date, the first date was used. DOR (months) = [progression/death date - first date of OR + 1]/30.4. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable was defined as not qualifying for CR, PR or PD. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. | Baseline up to the end of study (maximum of 5 years) |
| Overall Survival (OS) Probability at 12 Months in Phase 1b/2 Cohorts | OS probability was based on Kaplan-Meier method. OS was defined as the time from the start date to date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. | Baseline up to the end of study (maximum of 5 years) |
| Plasma Area Under the Curve From Zero to Infinite Time (AUCinf) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1 | Plasma area under the curve from zero to infinite time (AUCinf) of PF-06747775 as a single agent after single dose on Day -8 lead-in period in Phase 1 dose-escalation cohorts and on Day -4 lead-in period in Phase 2 Cohort 1. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | 1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1 |
| Maximum Concentration Observed After Dose Administration (Cmax) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1 | Cmax of PF-06747775 as a single agent after single dose on Day -8 lead-in period in Phase 1 dose-escalation cohorts and on Day -4 lead-in period in Phase 2 Cohort 1. Cmax was the maximum concentration after dose administration observed directly from the data. | 1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1 |
| Half-life (t1/2) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1 | Half-life (t1/2) of PF-06747775 as a single agent after single dose on Day -8 lead-in period in Phase 1 dose-escalation cohorts and on Day -4 lead-in period in Phase 2 Cohort 1. t1/2 was defined as the time measured for the plasma concentration to decrease by one half. | 1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1 |
| Apparent Clearance (CL/F) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1 | Apparent clearance (CL/F) of PF-06747775 as a single agent after single dose on Day -8 lead-in period in Phase 1 dose-escalation cohorts and on Day -4 lead-in period in Phase 2 Cohort 1. CL/F was calculated as: CL/F = dose / AUCinf. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | 1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1 |
| Volume of Distribution (Vz/F) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1 | Vz/F was defined as apparent volume of distribution. Vz/F was calculated as: Vz/F = dose / (AUCinf * kel). kel was defined as terminal phase rate constant and calculated by a linear regression of the log-linear concentration-time curve. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | 1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1 |
| Pre-dose Concentration at Steady State (Ctrough) of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B | Pre-dose concentration at steady state (Ctrough) of PF-06747775 as a single agent after multiple doses on Cycle 1 Day 11 in Phase 1 dose-escalation cohorts, Phase 2 Cohorts 1 and 2B. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data. | Pre-dose on Cycle 1 Day 11 |
| Area Under the Curve at Steady State (AUCtau) of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B | AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | 0 (pre-dose), 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 11 for Phase 1 dose-escalation cohorts; 0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose on Cycle 1 Day 11 for Phase 2 Cohorts 1 and 2B |
| CL/F of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B | CL/F of PF-06747775 as a single agent after multiple doses on Cycle 1 Day 11 in Phase 1 dose-escalation cohorts, Phase 2 Cohorts 1 and 2B. CL/F was calculated as: CL/F = dose / AUCtau. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | 0 (pre-dose), 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 11 for Phase 1 dose-escalation cohorts; 0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose for Phase 2 Cohorts 1 and 2B |
| Observed Accumulation Ratio (Rac) of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B | Rac was calculated as: Rac = (steady state AUCtau) / (single dose AUC24). AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. AUC24 was defined as area under the plasma concentration-time curve from time 0 to 24 hours. | 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -8 (dose-escalation cohorts) or -4 (Cohort 1); 0 (pre-dose), 1, 2, 4, 6, 8 (except for Cohort 1) and 24 hours post dose on Cycle 1 Day 11 for dose-escalation cohorts, Cohorts 1 and 2B |
| Steady State Accumulation Ratio (Rss) of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B | Steady state accumulation ratio (Rss) of PF-06747775 as a single agent after multiple doses on Cycle 1 Day 11 in Phase 1 dose-escalation cohorts, Phase 2 Cohorts 1 and 2B. Rss was calculated as: Rss = (steady state AUCtau) / (single dose AUCinf). AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | 1, 2, 4, 6, 8, 24, 48 and 72 hours post dose on Lead-in Day -8 (dose-escalation cohorts) or Day -4 (Cohort 1); 0 (pre-dose), 1, 2, 4, 6, 8 (except for Cohort 1) and 24 hours post dose on Cycle 1 Day 11 |
| AUCinf of Sildenafil Dosed Alone on Day -8 lead-in Period in Phase 1 Sildenafil Sub-study | AUCinf of sildenafil dosed alone and in combination with PF-06747775 200 mg or 300 mg on Day -8 lead-in period in Phase 1 Sildenafil sub-study. AUCinf was defined as area under the plasma concentration versus time curve from zero to extrapolated infinite time. | 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day -8 (+/- 3 days) in lead-in period |
| Cmax of Sildenafil Dosed Alone on Day -8 lead-in Period in Phase 1 Sildenafil Sub-study | Cmax values for sildenafil were analyzed using a mixed effects model with treatment as fixed effect and participant as random effect to estimate the effect of steady state PF-06747775 on sildenafil exposure. Cmax was the maximum concentration after dose administration observed directly from the data. | 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post dose on Day -8 (+/- 3 days) in lead-in period |
| CL/F of Sildenafil Dosed Alone on Day -8 lead-in Period in Phase 1 Sildenafil Sub-study | CL/F of sildenafil dosed alone on Day -8 lead-in period in Phase 1 Sildenafil sub-study. CL/F was calculated as: CL/F = dose / AUCinf. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post dose on Day -8 (+/- 3 days) in lead-in period |
| AUCinf of Sildenafil Dosed in Combination With PF-06747775 200 mg or 300 mg on Cycle 1 Day 11 in Phase 1 Sildenafil Sub-study | AUCinf of sildenafil dosed alone and in combination with PF-06747775 200 mg or 300 mg on Day -8 lead-in period in Phase 1 Sildenafil sub-study. AUCinf was defined as area under the plasma concentration versus time curve from zero to extrapolated infinite time. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 11 (+/- 4 days) |
| Cmax of Sildenafil Dosed in Combination With PF-06747775 200 mg or 300 mg on Cycle 1 Day 11 in Phase 1 Sildenafil Sub-study | Cmax values for sildenafil were analyzed using a mixed effects model with treatment as fixed effect and participant as random effect to estimate the effect of steady state PF-06747775 on sildenafil exposure. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 11 (+/- 4 days) |
| CL/F of Sildenafil Dosed in Combination With PF-06747775 200 mg or 300 mg on Cycle 1 Day 11 in Phase 1 Sildenafil Sub-study | CL/F of sildenafil dosed alone and in combination with PF-06747775 200 mg or 300 mg on Day -8 lead-in period and Cycle 1 Day 11 in Phase 1 Sildenafil sub-study. CL/F was calculated as: CL/F = dose / AUCinf. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 11 (+/- 4 days) |
| AUCtau of PF-06747775 at RP2D Under Fed and Overnight Fasted Conditions in Phase 1 Food Effect and Rifampin DDI Sub-study | AUCtau of PF-06747775 at the RP2D under fed and overnight fasted conditions in Phase 1 Food Effect and Rifampin DDI sub-study. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8 and 9 |
| Cmax of PF-06747775 at RP2D Under Fed and Overnight Fasted Conditions in Phase 1 Food Effect and Rifampin DDI Sub-study | Cmax of PF-06747775 at the RP2D under fed and overnight fasted conditions in Phase 1 Food Effect and Rifampin DDI sub-study. Cmax was the maximum concentration after dose administration observed directly from the data. | Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8 and 9 |
| AUCtau of PF-06747775 at RP2D When Dosed Alone and After Esomeprazole/Itraconazole Treatment in Phase 1 Esomeprazole-Itraconazole DDI Sub-study | AUCtau of PF-06747775 at the RP2D when dosed alone and after esomeprazole/itraconazole treatment in Phase 1 Esomeprazole-Itraconazole DDI sub-study. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8, 13 and 21 |
| Cmax of PF-06747775 at RP2D When Dosed Alone and After Esomeprazole/Itraconazole Treatment in Phase 1 Esomeprazole-Itraconazole DDI Sub-study | Cmax of PF-06747775 at RP2D when dosed alone and after esomeprazole/itraconazole treatment in Phase 1 Esomeprazole-Itraconazole DDI sub-study. Cmax was the maximum concentration after dose administration observed directly from the data. | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8, 13 and 21 |
| AUCtau of PF-06747775 at RP2D Dosed Alone and After Rifampin Treatment in Phase 1 Food Effect and Rifampin DDI Sub-study | AUCtau of PF-06747775 at RP2D dosed alone and after rifampin treatment in Phase 1 Food Effect and Rifampin DDI sub-study. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Day 21 |
| Cmax of PF-06747775 at RP2D Dosed Alone and After Rifampin Treatment in Phase 1 Food Effect and Rifampin DDI Sub-study | Cmax of PF-06747775 at RP2D dosed alone and after rifampin treatment in Phase 1 Food Effect and Rifampin DDI sub-study. Cmax was the maximum concentration after dose administration observed directly from the data. | Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Day 21 |
| AUCtau of PF-06747775 Following Multiple Doses When Given in Combination With Palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | AUCtau of PF-06747775 following multiple doses when given in combination with palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | 0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15 |
| Cmax of PF-06747775 Following Multiple Doses When Given in Combination With Palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | Cmax of PF-06747775 following multiple doses when given in combination with palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. Cmax was the maximum concentration after dose administration observed directly from the data. | 0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15 |
| CL/F of PF-06747775 Following Multiple Doses When Given in Combination With Palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | CL/F of PF-06747775 following multiple doses when given in combination with palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. CL/F was calculated as: CL/F = dose / AUCtau. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | 0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15 |
| Ctrough of PF-06747775 Following Multiple Doses When Given in Combination With Palbociclib on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | Ctrough of PF-06747775 following multiple doses when given in combination with palbociclib on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data. | Pre-dose on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 |
| Ctrough of PF-06747775 Following Multiple Doses When Given in Combination With Avelumab on Cycle 1 Day 15 in Phase 1b Cohort 3 | Ctrough of PF-06747775 following multiple doses when given in combination with avelumab on Cycle 1 Day 15 in Phase 1b Cohort 3. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data. | Pre-dose on Cycle 1 Day 15 |
| AUCtau of Palbociclib Following Multiple Doses When Given in Combination With PF-06747775 on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | AUCtau of palbociclib following multiple doses when given in combination with PF-06747775 on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | 0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15 |
| Cmax of Palbociclib Following Multiple Doses When Given in Combination With PF-06747775 on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | Cmax of palbociclib following multiple doses when given in combination with PF-06747775 on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. Cmax was the maximum concentration after dose administration observed directly from the data. | 0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15 |
| Ctrough of Palbociclib Following Multiple Doses When Given in Combination With PF-06747775 on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | Ctrough of palbociclib following multiple doses when given in combination with PF-06747775 on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 in Phase 1b/2 Cohorts 2A and 2B. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data. | Pre-dose on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 |
| Ctrough of Avelumab When Given in Combination With PF-06747775 on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3 | Ctrough of avelumab when given in combination with PF-06747775 on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data. | Pre-dose on Day 1 of Cycles 1-3 and Cycle 1 Day 15 |
| Cmax of Avelumab When Given in Combination With PF-06747775 on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3 | Cmax of avelumab when given in combination with PF-06747775 on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3. Cmax was the end of infusion peak concentration observed directly from data. | End of infusion of avelumab on Day 1 of Cycles 1-3 and Cycle 1 Day 15 |
| Number of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations in Tumor Tissue in All Cohorts All Phases | Number of participants with EGFR mutations in tumor tissue in all cohorts all phases. EGFR mutation assessments in tumor tissue included the mutations statuses of exon 19 deletion (del 19), exon 21 (L858R), G719X, L861Q, S768I, exon 20 insertions and T790M. | Baseline |
| Number of Participants With EGFR Mutations in Plasma in All Cohorts All Phases | Number of participants with EGFR mutations in plasma in all cohorts all phases. EGFR mutation assessments in plasma included the mutations statuses of exon 19 deletion (del 19), exon 21 (L858R) and T790M. | Baseline |
| Number of Participants With Positive Serum Anti-drug Antibody (ADA) of Avelumab in Phase 1b Cohort 3 | Number of participants with positive serum ADA of avelumab at pre-dose on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3. | Pre-dose on Day 1 of Cycles 1-3 and Cycle 1 Day 15 |
| AUCinf of PF-06747775 Following Single Dose on Lead-in Day -4 in Japan LIC RP2D Cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK Cohort | AUCinf of PF-06747775 following a 200 mg single dose on Lead-in Day -4 in Japan LIC RP2D cohort and Cycle 1 Day 1 in Japan LIC PK cohort, and following a 100 mg single dose on Lead-in Day -7 in Japan LIC PK cohort. AUCinf was defined as area under the plasma concentration versus time curve from zero to extrapolated infinite time. | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4 for Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 for Japan LIC PK cohort |
| Cmax of PF-06747775 Following Single Dose on Lead-in Day -4 in Japan LIC RP2D Cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK Cohort | Cmax of PF-06747775 following a 200 mg single dose on Lead-in Day -4 in Japan LIC RP2D cohort and Cycle 1 Day 1 in Japan LIC PK cohort, and following a 100 mg single dose on Lead-in Day -7 in Japan LIC PK cohort. Cmax was the maximum concentration observed from data. | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4 for Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 for Japan LIC PK cohort |
| Vz/F of PF-06747775 Following Single Dose on Lead-in Day -4 in Japan LIC RP2D Cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK Cohort | Vz/F of PF-06747775 following a 200 mg single dose on Lead-in Day -4 in Japan LIC RP2D cohort and Cycle 1 Day 1 in Japan LIC PK cohort, and following a 100 mg single dose on Lead-in Day -7 in Japan LIC PK cohort. Vz/F was defined as apparent volume of distribution. Vz/F was calculated as: Vz/F = dose / (AUCinf * kel). kel was defined as terminal phase rate constant and calculated by a linear regression of the log-linear concentration-time curve. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4 for Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 for Japan LIC PK cohort |
| t1/2 of PF-06747775 Following Single Dose on Lead-in Day -4 in Japan LIC RP2D Cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK Cohort | t1/2 of PF-06747775 following a 200 mg single dose on Lead-in Day -4 in Japan LIC RP2D cohort and Cycle 1 Day 1 in Japan LIC PK cohort, and following a 100 mg single dose on Lead-in Day -7 in Japan LIC PK cohort. t1/2 was defined as the time measured for the plasma concentration to decrease by one half. | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4 for Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 for Japan LIC PK cohort |
| AUCtau of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts | AUCtau of PF-06747775 following multiple doses on Cycle 1 Day 11 in Japan LIC RP2D cohort and Cycle 1 Day 15 in Japan LIC PK cohort. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Cycle 1 Day 11 (Japan LIC RP2D cohort) and Day 15 (Japan LIC PK cohort) |
| Ctrough of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts | Ctrough of PF-06747775 following multiple doses on Cycle 1 Day 11 in Japan LIC RP2D cohort and Cycle 1 Day 15 in Japan LIC PK cohort. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data. | Pre-dose on Cycle 1 Day 11 (Japan LIC RP2D cohort) and Day 15 (Japan LIC PK cohort) |
| Rac of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts | Rac of PF-06747775 following multiple doses on Cycle 1 Day 11 in Japan LIC RP2D cohort and Cycle 1 Day 15 in Japan LIC PK cohort. Rac was calculated as: Rac = (steady state AUCtau) / (single dose AUC24). AUC24 was defined as area under the plasma concentration-time curve from time 0 to 24 hours following single dose. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4, Cycle 1 Day 11 for Japan LIC RP2D cohort, Cycle 1 Days 1 and 15 for Japan LIC PK cohort |
| Rss of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts | Rss of PF-06747775 following multiple doses on Cycle 1 Day 11 in Japan RP2D cohort and Cycle 1 Day 15 in Japan PK cohort. Rss was calculated as: Rss = (steady state AUCtau) / (single dose AUCinf). AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4, Cycle 1 Day 11 for Japan LIC RP2D cohort, Cycle 1 Days 1 and 15 for Japan LIC PK cohort |
| CL/F of PF-06747775 Following Single and Multiple Doses in Japan LIC RP2D and PK Cohorts | CL/F of PF-06747775 following single dose on Lead-in Day -4 in Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK cohort, and following multiple doses on Cycle 1 Day 11 in Japan LIC RP2D cohort and on Cycle 1 Day 15 in Japan LIC PK cohort. CL/F was calculated as: CL/F = dose/AUCinf for single dose or dose/AUCtau for multiple doses. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4, Cycle 1 Day 11 for Japan LIC RP2D cohort, Lead-in Day-7, Days 1 and 15 for Japan LIC PK cohort |
| La Jolla |
| California |
| 92093 |
| United States |
| UC San Diego Medical Center - Hillcrest | San Diego | California | 92103 | United States |
| Smilow Cancer Hospital at Yale-New Haven | New Haven | Connecticut | 06510 | United States |
| UPMC Cancer Pavilion | Pittsburgh | Pennsylvania | 15232 | United States |
| UPMC Hillman Cancer Center | Pittsburgh | Pennsylvania | 15232 | United States |
| Seattle Cancer Care Alliance | Seattle | Washington | 98109 | United States |
| Chris O'Brien Lifehouse | Camperdown | New South Wales | 2050 | Australia |
| Royal Prince Alfred Hospital | Camperdown | New South Wales | 2050 | Australia |
| Prince Charles Hospital, Cancer Care Services | Chermside | Queensland | 4032 | Australia |
| National Hospital Organization Shikoku Cancer Center | Matsuyama | Ehime | 791-0280 | Japan |
| The Cancer Institute Hospital of JFCR | Koto-ku, Tokyo | 135-8550 | Japan |
| Seoul National University Hospital / Department of Internal Medicine | Seoul | 03080 | South Korea |
| Severance Hospital, Yonsei University Health System | Seoul | 03722 | South Korea |
| Asan Medical Center | Seoul | 05505 | South Korea |
Participants received a single oral dose of PF-06747775 50 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 50 mg QD for 21-day cycles (up to a maximum of 72 weeks). |
| FG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| FG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| FG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| FG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| FG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| FG007 | PF-06747775 200 mg QD Group | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous oral dosing of PF-06747775 200 mg QD for 21-day cycles (up to a maximum of 165 weeks). PF-06747775 200 mg QD group was a combined group of PF-06747775 200 mg QD + sildenafil 25 mg SD (Phase 1 Sildenafil sub-study), PF-06747775 200 mg QD + esomeprazole/itraconazole (Phase 1 Esomeprazole/Itraconazole sub-study), Japan Lead-in cohort (LIC) and Phase 2 Cohort 1. |
| FG008 | Phase 1 Sildenafil Sub-study: PF-06747775 300 mg QD + Sildenafil 25 mg SD | Participants received a single oral dose of sildenafil 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 121 weeks) plus a single oral dose of sildenafil 25 mg on Cycle 1 Day 11. |
| FG009 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). |
| FG010 | Phase 1 Food Effect and Rifampin DDI Sub-study: PF-06747775 + Rifampin | Participants were planned to receive continuous oral dosing of PF-06747775 at Recommended Phase 2 Dose (RP2D) QD for a 21-day cycles plus rifampin 600 mg QD through Day 10 to 21 of Cycle 1. No participants were enrolled or treated in this cohort prior to study termination. |
| FG011 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| FG012 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| FG013 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Participants with advanced epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer (NSCLC) were enrolled in this study. The safety analysis set included all enrolled patients who received at least 1 dose of study treatment. No enrollments occurred in Phase 1 Food Effect and Rifampin DDI sub-study, Phase 2 Cohort 2B or Phase 1b Cohort 3 prior to study termination.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1 Dose-escalation: PF-06747775 25 mg QD | Participants received a single oral dose of PF-06747775 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 25 mg once daily (QD) for 21-day cycles (up to a maximum of 95 weeks). |
| BG001 | Phase 1 Dose-escalation: PF-06747775 50 mg QD | Participants received a single oral dose of PF-06747775 50 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 50 mg QD for 21-day cycles (up to a maximum of 72 weeks). |
| BG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| BG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| BG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| BG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| BG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| BG007 | PF-06747775 200 mg QD Group | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous oral dosing of PF-06747775 200 mg QD for 21-day cycles (up to a maximum of 165 weeks). PF-06747775 200 mg QD group was a combined group of PF-06747775 200 mg QD + sildenafil 25 mg SD (Phase 1 Sildenafil sub-study), PF-06747775 200 mg QD + esomeprazole/itraconazole (Phase 1 Esomeprazole/Itraconazole sub-study), Japan Lead-in cohort (LIC) and Phase 2 Cohort 1. |
| BG008 | Phase 1 Sildenafil Sub-study: PF-06747775 300 mg QD + Sildenafil 25 mg SD | Participants received a single oral dose of sildenafil 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 121 weeks) plus a single oral dose of sildenafil 25 mg on Cycle 1 Day 11. |
| BG009 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). |
| BG010 | Phase 1 Food Effect and Rifampin DDI Sub-study: PF-06747775 + Rifampin | Participants were planned to receive continuous oral dosing of PF-06747775 at Recommended Phase 2 Dose (RP2D) QD for a 21-day cycles plus rifampin 600 mg QD through Day 10 to 21 of Cycle 1. No participants were enrolled or treated in this cohort prior to study termination. |
| BG011 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| BG012 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| BG013 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
| BG014 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Primary Diagnoses and Durations | Duration was since histopathological diagnosis in (years) to first dosing day or primary diagnosis visit date. | Median | Full Range | Years |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Dose Limiting Toxicities (DLTs) During the First Cycle in Phase 1 Dose-escalation Cohorts, Japan LIC and Phase 1b Cohort 3, and First 2 Cycles in Phase 1b Cohort 2A | DLT was defined as any of the following adverse events (AEs) occurring during the first cycle for Phase 1 dose-escalation cohorts, Japan LIC and Phase 1b Cohort 3, or the first 2 cycles for Phase 1b Cohort 2A of treatment, and considered attributable to study intervention: Grade 4 neutropenia >7 days; febrile neutropenia; Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade >=3 non-hematologic toxicities; Grade 4 rash, mucositis, or diarrhea; failure to receive at least 70% of planned doses; Grade 3 QTcF prolongation in asymptomatic participants; treatment-related AEs attributable to PF-06747775, palbociclib or both that caused palbociclib treatment delay >= 10 days or omission of at least 12 doses of the combination. Grade of AE was defined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. | The analysis population included participants in Phase 1 dose-escalation cohorts, Japan LIC, Phase 1b Cohorts 2A and 3 who were eligible, received study treatment and who either experienced a DLT during the first cycle of PF-06747775 or the first 2 cycles of PF 06747775 plus palbociclib, or completed the DLT observation period. | Posted | Count of Participants | Participants | 21 days for Phase 1 dose-escalation cohorts and Japan LIC; 42 days for Phase 1b Cohort 2A; 28 days for Phase 1b Cohort 3 |
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| Primary | Number of Participants With Confirmed Objective Response (OR) in PF-06747775 200 mg QD Group | Number of participants with confirmed OR according to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. Complete response (CR) was defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. | The response analysis population included all participants who received at least one dose of study medication, had measurable disease and adequate baseline assessment, and at least 1 post baseline assessment during the study. | Posted | Count of Participants | Participants | Baseline up to end of treatment (maximum of 165 weeks) |
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| Primary | Progression-free Survival (PFS) in Phase 2 Cohort 2B | PFS was based on Kaplan-Meier estimates. PFS was defined as the time from Cycle 1 Day 1 to the date of the first documentation of objective progression (PD) or death due to any cause. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. | The response analysis population included all participants who received at least one dose of study medication, had measurable disease and adequate baseline assessment, and at least 1 post baseline assessment during the study. | Posted | Cycle 1 Day 1 up to the end of study (maximum of 5 years) |
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| Secondary | Number of Participants With Treatment-emergent AEs (TEAEs) in All Cohorts All Phases (All-causality) | AE = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. Grade 3 (Severe) events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events = death related to an AE. Treatment-emergent events = between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. | The safety analysis population included all enrolled participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks) |
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| Secondary | Number of Participants With TEAEs in All Cohorts All Phases (Treatment-related) | Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Grade 3 (Severe) events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events = death related to an AE. Treatment-emergent events = between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Treatment-related AEs were determined by the investigator. | The safety analysis population included all enrolled participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks) |
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| Secondary | Number of Participants With Serious Adverse Events (SAEs) in All Cohorts All Phases | An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-related SAEs were determined by the investigator. | The safety analysis population included all enrolled participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks) |
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| Secondary | Number of Participants With Shifts of Laboratory Results From Grade <=2 at Baseline to Grade 3 or 4 Post-baseline in All Cohorts All Phases | Laboratory values included hemoglobin, platelets, white blood cell count (WBC), absolute (abs) neutrophils, abs lymphocytes, abs monocytes, abs eosinophils, abs basophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (Alk Phos), sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose, albumin, phosphorous or phosphate, prothrombin time (PT) or international normalized ratio (INR), partial thromboplastin time (PTT), urinalysis and pregnancy test. Grades of laboratory results were defined by NCI CTCAE version 4.03. Grade 3 (Severe) events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. | The safety analysis population included all enrolled participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Baseline up to the end of treatment (maximum of 195 weeks) |
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| Secondary | Number of Participants Meeting Categorical Criteria of QTcF Values When PF-06747775 Was Given as a Single Agent, and in Combination With Palbociclib and Avelumab. | Number of participants meeting categorical criteria of QTcF values when PF-06747775 was given as a single agent in Phase 1 dose-escalation cohorts, PF-06747775 200 mg QD group (only participants in Phase 2 Cohort 1 and Japan LIC were eligible for QTcF within this combined group), and in combination with palbociclib and avelumab in Phase 1b/2 Cohorts 2A, 2B and 3. Criteria for categorization of QTcF were defined as: maximum values 450 - <480 msec, 480 - <500 msec and >=500 msec. | QTcF analysis population included all treated participants who had at least 1 ECG assessment undertaken pre dose and 1 post dose at steady state in triplicate. | Posted | Count of Participants | Participants | Baseline up to Cycle 4 Day 1 (maximum of 10 weeks) |
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| Secondary | Number of Participants Meeting Categorical Criteria of QTcB Values When PF-06747775 Was Given as a Single Agent, and in Combination With Palbociclib and Avelumab. | Number of participants meeting categorical criteria of QTcB values when PF-06747775 was given as a single agent in Phase 1 dose-escalation cohorts, PF-06747775 200 mg QD group (only participants in Phase 2 Cohort 1 and Japan LIC were eligible for QTcB within this combined group), and in combination with palbociclib and avelumab in Phase 1b/2 Cohorts 2A, 2B and 3. Criteria for categorization of QTcB were defined as: maximum values 450 - <480 msec, 480 - <500 msec and >=500 msec. | QTcB analysis population included all treated participants who had at least 1 ECG assessment undertaken pre dose and 1 post dose at steady state in triplicate. | Posted | Count of Participants | Participants | Baseline up to Cycle 4 Day 1 (maximum of 10 weeks) |
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| Secondary | Number of Participants With Confirmed and Unconfirmed OR in Phase 1 Cohorts | Number of participants in Phase 1 cohorts with confirmed and unconfirmed OR according to RECIST v1.1. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable was defined as not qualifying for CR, PR or PD. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. Indeterminate was defined as progression not documented. | The response analysis population included all participants who received at least one dose of study medication, had measurable disease and adequate baseline assessment, and at least 1 post baseline assessment during the study. | Posted | Count of Participants | Participants | Baseline up to end of treatment (maximum of 195 weeks) |
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| Secondary | Objective Response Rate (ORR) in Phase 1b/2 Cohorts 2A, 2B and 3 | ORR was defined as percentage of participants with OR based assessment of CR or PR according to RECIST v1.1 that must have been confirmed ≥4 weeks later. Participants who did not have an on treatment radiographic tumor assessment due to early progression, who received anti tumor treatment other than the study medication prior to reaching a CR or PR, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR were counted as non responders in the assessment of ORR. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. | The response analysis population included all participants who received at least one dose of study medication, had measurable disease and adequate baseline assessment, and at least 1 post baseline assessment during the study. | Posted | Number | 90% Confidence Interval | Percentage of participants | Baseline up to end of treatment (maximum of 108 weeks) |
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| Secondary | PFS in PF-06747775 200 mg QD Group, Phase 1b Cohorts 2A and 3 | PFS was based on Kaplan-Meier estimates. PFS was defined as the time from Cycle 1 Day 1 to the date of the first documentation of PD or death due to any cause. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. | The response analysis population included all participants who received at least one dose of study medication, had measurable disease and adequate baseline assessment, and at least 1 post baseline assessment during the study. | Posted | Median | 90% Confidence Interval | Months | Cycle 1 Day 1 up to the end of study (maximum of 5 years) |
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| Secondary | Duration of Objective Response (DOR) in Phase 1b/2 Cohorts | DOR was the time from the date of first documentation of confirmed CR or PR to the date of first documentation of PD or death due to any cause. If tumor progression data included more than 1 date, the first date was used. DOR (months) = [progression/death date - first date of OR + 1]/30.4. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable was defined as not qualifying for CR, PR or PD. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. | The response analysis population included all participants who received at least one dose of study medication, had measurable disease and adequate baseline assessment, and at least 1 post baseline assessment during the study. | Posted | Median | Full Range | Months | Baseline up to the end of study (maximum of 5 years) |
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| Secondary | Overall Survival (OS) Probability at 12 Months in Phase 1b/2 Cohorts | OS probability was based on Kaplan-Meier method. OS was defined as the time from the start date to date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. | The response analysis population included all participants who received at least one dose of study medication, had measurable disease and adequate baseline assessment, and at least 1 post baseline assessment during the study. | Posted | Number | 90% Confidence Interval | Percentage of participants | Baseline up to the end of study (maximum of 5 years) |
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| Secondary | Plasma Area Under the Curve From Zero to Infinite Time (AUCinf) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1 | Plasma area under the curve from zero to infinite time (AUCinf) of PF-06747775 as a single agent after single dose on Day -8 lead-in period in Phase 1 dose-escalation cohorts and on Day -4 lead-in period in Phase 2 Cohort 1. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1 |
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| Secondary | Maximum Concentration Observed After Dose Administration (Cmax) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1 | Cmax of PF-06747775 as a single agent after single dose on Day -8 lead-in period in Phase 1 dose-escalation cohorts and on Day -4 lead-in period in Phase 2 Cohort 1. Cmax was the maximum concentration after dose administration observed directly from the data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1 |
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| Secondary | Half-life (t1/2) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1 | Half-life (t1/2) of PF-06747775 as a single agent after single dose on Day -8 lead-in period in Phase 1 dose-escalation cohorts and on Day -4 lead-in period in Phase 2 Cohort 1. t1/2 was defined as the time measured for the plasma concentration to decrease by one half. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Mean | Standard Deviation | hrs | 1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1 |
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| Secondary | Apparent Clearance (CL/F) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1 | Apparent clearance (CL/F) of PF-06747775 as a single agent after single dose on Day -8 lead-in period in Phase 1 dose-escalation cohorts and on Day -4 lead-in period in Phase 2 Cohort 1. CL/F was calculated as: CL/F = dose / AUCinf. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | 1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1 |
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| Secondary | Volume of Distribution (Vz/F) of PF-06747775 as a Single Agent After Single Dose on Day -8 lead-in Period in Phase 1 Dose-escalation Cohorts and on Day -4 lead-in Period in Phase 2 Cohort 1 | Vz/F was defined as apparent volume of distribution. Vz/F was calculated as: Vz/F = dose / (AUCinf * kel). kel was defined as terminal phase rate constant and calculated by a linear regression of the log-linear concentration-time curve. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | 1, 2, 4, 6, 8, 24, 48 and 72 hours post-dose on Day -8 (+/- 3 days) in lead-in period for Phase 1 dose-escalation cohorts and on Day -4 in lead-in period for Phase 2 Cohort 1 |
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| Secondary | Pre-dose Concentration at Steady State (Ctrough) of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B | Pre-dose concentration at steady state (Ctrough) of PF-06747775 as a single agent after multiple doses on Cycle 1 Day 11 in Phase 1 dose-escalation cohorts, Phase 2 Cohorts 1 and 2B. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose on Cycle 1 Day 11 |
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| Secondary | Area Under the Curve at Steady State (AUCtau) of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B | AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 0 (pre-dose), 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 11 for Phase 1 dose-escalation cohorts; 0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose on Cycle 1 Day 11 for Phase 2 Cohorts 1 and 2B |
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| Secondary | CL/F of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B | CL/F of PF-06747775 as a single agent after multiple doses on Cycle 1 Day 11 in Phase 1 dose-escalation cohorts, Phase 2 Cohorts 1 and 2B. CL/F was calculated as: CL/F = dose / AUCtau. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | 0 (pre-dose), 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 11 for Phase 1 dose-escalation cohorts; 0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose for Phase 2 Cohorts 1 and 2B |
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| Secondary | Observed Accumulation Ratio (Rac) of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B | Rac was calculated as: Rac = (steady state AUCtau) / (single dose AUC24). AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. AUC24 was defined as area under the plasma concentration-time curve from time 0 to 24 hours. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -8 (dose-escalation cohorts) or -4 (Cohort 1); 0 (pre-dose), 1, 2, 4, 6, 8 (except for Cohort 1) and 24 hours post dose on Cycle 1 Day 11 for dose-escalation cohorts, Cohorts 1 and 2B |
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| Secondary | Steady State Accumulation Ratio (Rss) of PF-06747775 as a Single Agent After Multiple Doses on Cycle 1 Day 11 in Phase 1 Dose-escalation Cohorts and Phase 2 Cohorts 1 and 2B | Steady state accumulation ratio (Rss) of PF-06747775 as a single agent after multiple doses on Cycle 1 Day 11 in Phase 1 dose-escalation cohorts, Phase 2 Cohorts 1 and 2B. Rss was calculated as: Rss = (steady state AUCtau) / (single dose AUCinf). AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 1, 2, 4, 6, 8, 24, 48 and 72 hours post dose on Lead-in Day -8 (dose-escalation cohorts) or Day -4 (Cohort 1); 0 (pre-dose), 1, 2, 4, 6, 8 (except for Cohort 1) and 24 hours post dose on Cycle 1 Day 11 |
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| Secondary | AUCinf of Sildenafil Dosed Alone on Day -8 lead-in Period in Phase 1 Sildenafil Sub-study | AUCinf of sildenafil dosed alone and in combination with PF-06747775 200 mg or 300 mg on Day -8 lead-in period in Phase 1 Sildenafil sub-study. AUCinf was defined as area under the plasma concentration versus time curve from zero to extrapolated infinite time. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day -8 (+/- 3 days) in lead-in period |
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| Secondary | Cmax of Sildenafil Dosed Alone on Day -8 lead-in Period in Phase 1 Sildenafil Sub-study | Cmax values for sildenafil were analyzed using a mixed effects model with treatment as fixed effect and participant as random effect to estimate the effect of steady state PF-06747775 on sildenafil exposure. Cmax was the maximum concentration after dose administration observed directly from the data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post dose on Day -8 (+/- 3 days) in lead-in period |
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| Secondary | CL/F of Sildenafil Dosed Alone on Day -8 lead-in Period in Phase 1 Sildenafil Sub-study | CL/F of sildenafil dosed alone on Day -8 lead-in period in Phase 1 Sildenafil sub-study. CL/F was calculated as: CL/F = dose / AUCinf. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post dose on Day -8 (+/- 3 days) in lead-in period |
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| Secondary | AUCinf of Sildenafil Dosed in Combination With PF-06747775 200 mg or 300 mg on Cycle 1 Day 11 in Phase 1 Sildenafil Sub-study | AUCinf of sildenafil dosed alone and in combination with PF-06747775 200 mg or 300 mg on Day -8 lead-in period in Phase 1 Sildenafil sub-study. AUCinf was defined as area under the plasma concentration versus time curve from zero to extrapolated infinite time. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 11 (+/- 4 days) |
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| Secondary | Cmax of Sildenafil Dosed in Combination With PF-06747775 200 mg or 300 mg on Cycle 1 Day 11 in Phase 1 Sildenafil Sub-study | Cmax values for sildenafil were analyzed using a mixed effects model with treatment as fixed effect and participant as random effect to estimate the effect of steady state PF-06747775 on sildenafil exposure. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 11 (+/- 4 days) |
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| Secondary | CL/F of Sildenafil Dosed in Combination With PF-06747775 200 mg or 300 mg on Cycle 1 Day 11 in Phase 1 Sildenafil Sub-study | CL/F of sildenafil dosed alone and in combination with PF-06747775 200 mg or 300 mg on Day -8 lead-in period and Cycle 1 Day 11 in Phase 1 Sildenafil sub-study. CL/F was calculated as: CL/F = dose / AUCinf. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 11 (+/- 4 days) |
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| Secondary | AUCtau of PF-06747775 at RP2D Under Fed and Overnight Fasted Conditions in Phase 1 Food Effect and Rifampin DDI Sub-study | AUCtau of PF-06747775 at the RP2D under fed and overnight fasted conditions in Phase 1 Food Effect and Rifampin DDI sub-study. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8 and 9 |
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| Secondary | Cmax of PF-06747775 at RP2D Under Fed and Overnight Fasted Conditions in Phase 1 Food Effect and Rifampin DDI Sub-study | Cmax of PF-06747775 at the RP2D under fed and overnight fasted conditions in Phase 1 Food Effect and Rifampin DDI sub-study. Cmax was the maximum concentration after dose administration observed directly from the data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8 and 9 |
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| Secondary | AUCtau of PF-06747775 at RP2D When Dosed Alone and After Esomeprazole/Itraconazole Treatment in Phase 1 Esomeprazole-Itraconazole DDI Sub-study | AUCtau of PF-06747775 at the RP2D when dosed alone and after esomeprazole/itraconazole treatment in Phase 1 Esomeprazole-Itraconazole DDI sub-study. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8, 13 and 21 |
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| Secondary | Cmax of PF-06747775 at RP2D When Dosed Alone and After Esomeprazole/Itraconazole Treatment in Phase 1 Esomeprazole-Itraconazole DDI Sub-study | Cmax of PF-06747775 at RP2D when dosed alone and after esomeprazole/itraconazole treatment in Phase 1 Esomeprazole-Itraconazole DDI sub-study. Cmax was the maximum concentration after dose administration observed directly from the data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Days 8, 13 and 21 |
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| Secondary | AUCtau of PF-06747775 at RP2D Dosed Alone and After Rifampin Treatment in Phase 1 Food Effect and Rifampin DDI Sub-study | AUCtau of PF-06747775 at RP2D dosed alone and after rifampin treatment in Phase 1 Food Effect and Rifampin DDI sub-study. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Day 21 |
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| Secondary | Cmax of PF-06747775 at RP2D Dosed Alone and After Rifampin Treatment in Phase 1 Food Effect and Rifampin DDI Sub-study | Cmax of PF-06747775 at RP2D dosed alone and after rifampin treatment in Phase 1 Food Effect and Rifampin DDI sub-study. Cmax was the maximum concentration after dose administration observed directly from the data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Pre-dose, 1, 2, 4, 6, 8 and 24 hours post dose of PF-06747775 on Cycle 1 Day 21 |
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| Secondary | AUCtau of PF-06747775 Following Multiple Doses When Given in Combination With Palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | AUCtau of PF-06747775 following multiple doses when given in combination with palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15 |
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| Secondary | Cmax of PF-06747775 Following Multiple Doses When Given in Combination With Palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | Cmax of PF-06747775 following multiple doses when given in combination with palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. Cmax was the maximum concentration after dose administration observed directly from the data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15 |
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| Secondary | CL/F of PF-06747775 Following Multiple Doses When Given in Combination With Palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | CL/F of PF-06747775 following multiple doses when given in combination with palbociclib on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. CL/F was calculated as: CL/F = dose / AUCtau. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | 0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15 |
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| Secondary | Ctrough of PF-06747775 Following Multiple Doses When Given in Combination With Palbociclib on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | Ctrough of PF-06747775 following multiple doses when given in combination with palbociclib on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 |
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| Secondary | Ctrough of PF-06747775 Following Multiple Doses When Given in Combination With Avelumab on Cycle 1 Day 15 in Phase 1b Cohort 3 | Ctrough of PF-06747775 following multiple doses when given in combination with avelumab on Cycle 1 Day 15 in Phase 1b Cohort 3. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Pre-dose on Cycle 1 Day 15 |
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| Secondary | AUCtau of Palbociclib Following Multiple Doses When Given in Combination With PF-06747775 on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | AUCtau of palbociclib following multiple doses when given in combination with PF-06747775 on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15 |
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| Secondary | Cmax of Palbociclib Following Multiple Doses When Given in Combination With PF-06747775 on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | Cmax of palbociclib following multiple doses when given in combination with PF-06747775 on Cycle 1 Day 15 in Phase 1b Cohort 2A and Phase 2 Cohort 2B. Cmax was the maximum concentration after dose administration observed directly from the data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0 (pre-dose), 1, 2, 4, 6 and 24 hours post dose on Cycle 1 Day 15 |
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| Secondary | Ctrough of Palbociclib Following Multiple Doses When Given in Combination With PF-06747775 on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 in Phase 1b Cohort 2A and Phase 2 Cohort 2B | Ctrough of palbociclib following multiple doses when given in combination with PF-06747775 on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 in Phase 1b/2 Cohorts 2A and 2B. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose on Day 15 of Cycles 1-2 and Day 1 of Cycles 2-4 |
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| Secondary | Ctrough of Avelumab When Given in Combination With PF-06747775 on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3 | Ctrough of avelumab when given in combination with PF-06747775 on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Pre-dose on Day 1 of Cycles 1-3 and Cycle 1 Day 15 |
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| Secondary | Cmax of Avelumab When Given in Combination With PF-06747775 on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3 | Cmax of avelumab when given in combination with PF-06747775 on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3. Cmax was the end of infusion peak concentration observed directly from data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | End of infusion of avelumab on Day 1 of Cycles 1-3 and Cycle 1 Day 15 |
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| Secondary | Number of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations in Tumor Tissue in All Cohorts All Phases | Number of participants with EGFR mutations in tumor tissue in all cohorts all phases. EGFR mutation assessments in tumor tissue included the mutations statuses of exon 19 deletion (del 19), exon 21 (L858R), G719X, L861Q, S768I, exon 20 insertions and T790M. | The biomarker analysis set is defined as all participants in the safety analysis set who had at least one screening and post treatment biomarker assessment. | Posted | Count of Participants | Participants | Baseline |
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| Secondary | Number of Participants With EGFR Mutations in Plasma in All Cohorts All Phases | Number of participants with EGFR mutations in plasma in all cohorts all phases. EGFR mutation assessments in plasma included the mutations statuses of exon 19 deletion (del 19), exon 21 (L858R) and T790M. | The biomarker analysis set is defined as all participants in the safety analysis set who had at least one screening and post treatment biomarker assessment. | Posted | Count of Participants | Participants | Baseline |
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| Secondary | Number of Participants With Positive Serum Anti-drug Antibody (ADA) of Avelumab in Phase 1b Cohort 3 | Number of participants with positive serum ADA of avelumab at pre-dose on Day 1 of Cycles 1-3 and Cycle 1 Day 15 in Phase 1b Cohort 3. | The immunogenicity analysis set included participants who had at least one ADA sample collected for avelumab. | Posted | Pre-dose on Day 1 of Cycles 1-3 and Cycle 1 Day 15 |
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| Secondary | AUCinf of PF-06747775 Following Single Dose on Lead-in Day -4 in Japan LIC RP2D Cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK Cohort | AUCinf of PF-06747775 following a 200 mg single dose on Lead-in Day -4 in Japan LIC RP2D cohort and Cycle 1 Day 1 in Japan LIC PK cohort, and following a 100 mg single dose on Lead-in Day -7 in Japan LIC PK cohort. AUCinf was defined as area under the plasma concentration versus time curve from zero to extrapolated infinite time. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4 for Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 for Japan LIC PK cohort |
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| Secondary | Cmax of PF-06747775 Following Single Dose on Lead-in Day -4 in Japan LIC RP2D Cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK Cohort | Cmax of PF-06747775 following a 200 mg single dose on Lead-in Day -4 in Japan LIC RP2D cohort and Cycle 1 Day 1 in Japan LIC PK cohort, and following a 100 mg single dose on Lead-in Day -7 in Japan LIC PK cohort. Cmax was the maximum concentration observed from data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4 for Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 for Japan LIC PK cohort |
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| Secondary | Vz/F of PF-06747775 Following Single Dose on Lead-in Day -4 in Japan LIC RP2D Cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK Cohort | Vz/F of PF-06747775 following a 200 mg single dose on Lead-in Day -4 in Japan LIC RP2D cohort and Cycle 1 Day 1 in Japan LIC PK cohort, and following a 100 mg single dose on Lead-in Day -7 in Japan LIC PK cohort. Vz/F was defined as apparent volume of distribution. Vz/F was calculated as: Vz/F = dose / (AUCinf * kel). kel was defined as terminal phase rate constant and calculated by a linear regression of the log-linear concentration-time curve. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4 for Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 for Japan LIC PK cohort |
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| Secondary | t1/2 of PF-06747775 Following Single Dose on Lead-in Day -4 in Japan LIC RP2D Cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK Cohort | t1/2 of PF-06747775 following a 200 mg single dose on Lead-in Day -4 in Japan LIC RP2D cohort and Cycle 1 Day 1 in Japan LIC PK cohort, and following a 100 mg single dose on Lead-in Day -7 in Japan LIC PK cohort. t1/2 was defined as the time measured for the plasma concentration to decrease by one half. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Mean | Standard Deviation | hrs | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4 for Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 for Japan LIC PK cohort |
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| Secondary | AUCtau of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts | AUCtau of PF-06747775 following multiple doses on Cycle 1 Day 11 in Japan LIC RP2D cohort and Cycle 1 Day 15 in Japan LIC PK cohort. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCtau was calculated using Linear/Log trapezoidal method. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Cycle 1 Day 11 (Japan LIC RP2D cohort) and Day 15 (Japan LIC PK cohort) |
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| Secondary | Ctrough of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts | Ctrough of PF-06747775 following multiple doses on Cycle 1 Day 11 in Japan LIC RP2D cohort and Cycle 1 Day 15 in Japan LIC PK cohort. Ctrough was defined as pre-dose concentration during multiple dosing and observed directly from data. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose on Cycle 1 Day 11 (Japan LIC RP2D cohort) and Day 15 (Japan LIC PK cohort) |
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| Secondary | Rac of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts | Rac of PF-06747775 following multiple doses on Cycle 1 Day 11 in Japan LIC RP2D cohort and Cycle 1 Day 15 in Japan LIC PK cohort. Rac was calculated as: Rac = (steady state AUCtau) / (single dose AUC24). AUC24 was defined as area under the plasma concentration-time curve from time 0 to 24 hours following single dose. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4, Cycle 1 Day 11 for Japan LIC RP2D cohort, Cycle 1 Days 1 and 15 for Japan LIC PK cohort |
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| Secondary | Rss of PF-06747775 Following Multiple Doses in Japan LIC RP2D and PK Cohorts | Rss of PF-06747775 following multiple doses on Cycle 1 Day 11 in Japan RP2D cohort and Cycle 1 Day 15 in Japan PK cohort. Rss was calculated as: Rss = (steady state AUCtau) / (single dose AUCinf). AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4, Cycle 1 Day 11 for Japan LIC RP2D cohort, Cycle 1 Days 1 and 15 for Japan LIC PK cohort |
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| Secondary | CL/F of PF-06747775 Following Single and Multiple Doses in Japan LIC RP2D and PK Cohorts | CL/F of PF-06747775 following single dose on Lead-in Day -4 in Japan LIC RP2D cohort, Lead-in Day -7 and Cycle 1 Day 1 in Japan LIC PK cohort, and following multiple doses on Cycle 1 Day 11 in Japan LIC RP2D cohort and on Cycle 1 Day 15 in Japan LIC PK cohort. CL/F was calculated as: CL/F = dose/AUCinf for single dose or dose/AUCtau for multiple doses. AUCtau was defined as area under the plasma concentration-time profile from time zero to tau, the dosing interval, where tau = 24 hours. AUCinf was area under the plasma concentration versus time curve (AUC) from zero to extrapolated infinite time. | The PK parameter analysis population included all treated participants who had sufficient information to estimate at least 1 of the PK parameters of interest for a particular analyte. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | 0 (pre-dose), 1, 2, 4, 6, 8 and 24 hours post dose on Lead-in Day -4, Cycle 1 Day 11 for Japan LIC RP2D cohort, Lead-in Day-7, Days 1 and 15 for Japan LIC PK cohort |
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Baseline up to 28 days after last dose of study drug (up to a maximum of 199 weeks).
The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase 1 Dose-escalation: PF-06747775 25 mg QD | Participants received a single oral dose of PF-06747775 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 25 mg once daily (QD) for 21-day cycles (up to a maximum of 95 weeks). | 0 | 4 | 2 | 4 | 4 | 4 |
| EG001 | Phase 1 Dose-escalation: PF-06747775 50 mg QD | Participants received a single oral dose of PF-06747775 50 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 50 mg QD for 21-day cycles (up to a maximum of 72 weeks). | 1 | 3 | 1 | 3 | 3 | 3 |
| EG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). | 0 | 4 | 3 | 4 | 4 | 4 |
| EG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). | 0 | 4 | 3 | 4 | 4 | 4 |
| EG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). | 0 | 3 | 0 | 3 | 3 | 3 |
| EG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). | 1 | 4 | 3 | 4 | 4 | 4 |
| EG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). | 1 | 4 | 2 | 4 | 4 | 4 |
| EG007 | PF-06747775 200 mg QD Group | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous oral dosing of PF-06747775 200 mg QD for 21-day cycles (up to a maximum of 165 weeks). PF-06747775 200 mg QD group was a combined group of PF-06747775 200 mg QD + sildenafil 25 mg SD (Phase 1 Sildenafil sub-study), PF-06747775 200 mg QD + esomeprazole/itraconazole (Phase 1 Esomeprazole/Itraconazole sub-study), Japan Lead-in cohort (LIC) and Phase 2 Cohort 1. | 0 | 29 | 3 | 29 | 29 | 29 |
| EG008 | Phase 1 Sildenafil Sub-study: PF-06747775 300 mg QD + Sildenafil 25 mg SD | Participants received a single oral dose of sildenafil 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 121 weeks) plus a single oral dose of sildenafil 25 mg on Cycle 1 Day 11. | 0 | 5 | 0 | 5 | 5 | 5 |
| EG009 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). | 0 | 5 | 1 | 5 | 5 | 5 |
| EG010 | Phase 1 Food Effect and Rifampin DDI Sub-study: PF-06747775 + Rifampin | Participants were planned to receive continuous oral dosing of PF-06747775 at Recommended Phase 2 Dose (RP2D) QD for a 21-day cycles plus rifampin 600 mg QD through Day 10 to 21 of Cycle 1. No participants were enrolled or treated in this cohort prior to study termination. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG011 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG012 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG013 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. | 0 | 0 | 0 | 0 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Angina pectoris | Cardiac disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Intracardiac thrombus | Cardiac disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Disease progression | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Joint abscess | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA v23.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Haemarthrosis | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v23.0 | Non-systematic Assessment |
| |
| Brain oedema | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dysarthria | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Bundle branch block right | Cardiac disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Congestive cardiomyopathy | Cardiac disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hypoacusis | Ear and labyrinth disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Conjunctival oedema | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Corneal erosion | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Erythema of eyelid | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Eye irritation | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Eyelid rash | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Eyelids pruritus | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Growth of eyelashes | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Macular degeneration | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pterygium | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Trichomegaly | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Vitreous haemorrhage | Eye disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Anal inflammation | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Oesophageal pain | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Oedema | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Anal fungal infection | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Enterocolitis infectious | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Helicobacter gastritis | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Onychomycosis | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Staphylococcal skin infection | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Tinea cruris | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Compression fracture | Injury, poisoning and procedural complications | MedDRA v23.0 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA v23.0 | Non-systematic Assessment |
| |
| Fracture | Injury, poisoning and procedural complications | MedDRA v23.0 | Non-systematic Assessment |
| |
| Fractured sacrum | Injury, poisoning and procedural complications | MedDRA v23.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Blood calcium decreased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Blood sodium decreased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Creatinine renal clearance decreased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Oxygen saturation decreased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Weight increased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA v23.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hypophagia | Metabolism and nutrition disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v23.0 | Non-systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Balance disorder | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Facial paralysis | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Azotaemia | Renal and urinary disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Prostatic obstruction | Reproductive system and breast disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Vulvovaginal pain | Reproductive system and breast disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Vulvovaginal rash | Reproductive system and breast disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Nasal dryness | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Nasal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Paranasal sinus discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Sputum discoloured | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Upper respiratory tract inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hair texture abnormal | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Ingrowing nail | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Intertrigo | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Onychomadesis | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA v23.0 | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 5, 2017 | May 13, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C500026 | palbociclib |
| C000609138 | avelumab |
Not provided
Not provided
Not provided
| Male |
|
| Asian |
|
| Other |
|
| Unspecified |
|
| Lung adenocarcinoma |
|
| Lung adenocarcinoma stage IV |
|
| Non-small cell lung cancer stage IV |
|
| Squamous cell carcinoma |
|
| Lung neoplasm malignant |
|
| Non-small cell lung cancer |
|
| Adenocarcinoma metastatic |
|
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | Japan LIC | Japan LIC included Japan LIC RP2D cohort and Japan LIC PK cohort. Japanese participants received a single oral dose of PF-06747775 200 mg on Day -4 (Japan LIC RP2D cohort) or PF-06747775 100 mg on Day -7 (Japan LIC PK cohort) in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycles. (up to a maximum of 61 weeks). |
| OG008 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). |
| OG009 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
|
|
| Units | Counts |
|---|
| Participants |
|
| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | PF-06747775 200 mg QD Group | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous oral dosing of PF-06747775 200 mg QD for 21-day cycles (up to a maximum of 165 weeks). PF-06747775 200 mg QD group was a combined group of PF-06747775 200 mg QD + sildenafil 25 mg SD (Phase 1 Sildenafil sub-study), PF-06747775 200 mg QD + esomeprazole/itraconazole (Phase 1 Esomeprazole/Itraconazole sub-study), Japan Lead-in cohort (LIC) and Phase 2 Cohort 1. |
| OG008 | Phase 1 Sildenafil Sub-study: PF-06747775 300 mg QD + Sildenafil 25 mg SD | Participants received a single oral dose of sildenafil 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 121 weeks) plus a single oral dose of sildenafil 25 mg on Cycle 1 Day 11. |
| OG009 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). |
| OG010 | Phase 1 Food Effect and Rifampin DDI Sub-study: PF-06747775 + Rifampin | Participants were planned to receive continuous oral dosing of PF-06747775 at Recommended Phase 2 Dose (RP2D) QD for a 21-day cycles plus rifampin 600 mg QD through Day 10 to 21 of Cycle 1. No participants were enrolled or treated in this cohort prior to study termination. |
| OG011 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG012 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG013 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
|
|
| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | PF-06747775 200 mg QD Group | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous oral dosing of PF-06747775 200 mg QD for 21-day cycles (up to a maximum of 165 weeks). PF-06747775 200 mg QD group was a combined group of PF-06747775 200 mg QD + sildenafil 25 mg SD (Phase 1 Sildenafil sub-study), PF-06747775 200 mg QD + esomeprazole/itraconazole (Phase 1 Esomeprazole/Itraconazole sub-study), Japan Lead-in cohort (LIC) and Phase 2 Cohort 1. |
| OG008 | Phase 1 Sildenafil Sub-study: PF-06747775 300 mg QD + Sildenafil 25 mg SD | Participants received a single oral dose of sildenafil 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 121 weeks) plus a single oral dose of sildenafil 25 mg on Cycle 1 Day 11. |
| OG009 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). |
| OG010 | Phase 1 Food Effect and Rifampin DDI Sub-study: PF-06747775 + Rifampin | Participants were planned to receive continuous oral dosing of PF-06747775 at Recommended Phase 2 Dose (RP2D) QD for a 21-day cycles plus rifampin 600 mg QD through Day 10 to 21 of Cycle 1. No participants were enrolled or treated in this cohort prior to study termination. |
| OG011 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG012 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG013 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
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Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | PF-06747775 200 mg QD Group | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous oral dosing of PF-06747775 200 mg QD for 21-day cycles (up to a maximum of 165 weeks). PF-06747775 200 mg QD group was a combined group of PF-06747775 200 mg QD + sildenafil 25 mg SD (Phase 1 Sildenafil sub-study), PF-06747775 200 mg QD + esomeprazole/itraconazole (Phase 1 Esomeprazole/Itraconazole sub-study), Japan Lead-in cohort (LIC) and Phase 2 Cohort 1. |
| OG008 | Phase 1 Sildenafil Sub-study: PF-06747775 300 mg QD + Sildenafil 25 mg SD | Participants received a single oral dose of sildenafil 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 121 weeks) plus a single oral dose of sildenafil 25 mg on Cycle 1 Day 11. |
| OG009 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). |
| OG010 | Phase 1 Food Effect and Rifampin DDI Sub-study: PF-06747775 + Rifampin | Participants were planned to receive continuous oral dosing of PF-06747775 at Recommended Phase 2 Dose (RP2D) QD for a 21-day cycles plus rifampin 600 mg QD through Day 10 to 21 of Cycle 1. No participants were enrolled or treated in this cohort prior to study termination. |
| OG011 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG012 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG013 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
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Participants received a single oral dose of PF-06747775 50 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 50 mg QD for 21-day cycles (up to a maximum of 72 weeks). |
| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | PF-06747775 200 mg QD Group | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous oral dosing of PF-06747775 200 mg QD for 21-day cycles (up to a maximum of 165 weeks). PF-06747775 200 mg QD group was a combined group of PF-06747775 200 mg QD + sildenafil 25 mg SD (Phase 1 Sildenafil sub-study), PF-06747775 200 mg QD + esomeprazole/itraconazole (Phase 1 Esomeprazole/Itraconazole sub-study), Japan Lead-in cohort (LIC) and Phase 2 Cohort 1. |
| OG008 | Phase 1 Sildenafil Sub-study: PF-06747775 300 mg QD + Sildenafil 25 mg SD | Participants received a single oral dose of sildenafil 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 121 weeks) plus a single oral dose of sildenafil 25 mg on Cycle 1 Day 11. |
| OG009 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). |
| OG010 | Phase 1 Food Effect and Rifampin DDI Sub-study: PF-06747775 + Rifampin | Participants were planned to receive continuous oral dosing of PF-06747775 at Recommended Phase 2 Dose (RP2D) QD for a 21-day cycles plus rifampin 600 mg QD through Day 10 to 21 of Cycle 1. No participants were enrolled or treated in this cohort prior to study termination. |
| OG011 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG012 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG013 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
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| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | PF-06747775 200 mg QD Group | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous oral dosing of PF-06747775 200 mg QD for 21-day cycles (up to a maximum of 165 weeks). PF-06747775 200 mg QD group was a combined group of PF-06747775 200 mg QD + sildenafil 25 mg SD (Phase 1 Sildenafil sub-study), PF-06747775 200 mg QD + esomeprazole/itraconazole (Phase 1 Esomeprazole/Itraconazole sub-study), Japan Lead-in cohort (LIC) and Phase 2 Cohort 1. |
| OG008 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). |
| OG009 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG010 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG011 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
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| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | PF-06747775 200 mg QD Group | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous oral dosing of PF-06747775 200 mg QD for 21-day cycles (up to a maximum of 165 weeks). PF-06747775 200 mg QD group was a combined group of PF-06747775 200 mg QD + sildenafil 25 mg SD (Phase 1 Sildenafil sub-study), PF-06747775 200 mg QD + esomeprazole/itraconazole (Phase 1 Esomeprazole/Itraconazole sub-study), Japan Lead-in cohort (LIC) and Phase 2 Cohort 1. |
| OG008 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). |
| OG009 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG010 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG011 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
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| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | Phase 1 Sildenafil Sub-study: PF-06747775 300 mg QD + Sildenafil 25 mg SD | Participants received a single oral dose of sildenafil 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 121 weeks) plus a single oral dose of sildenafil 25 mg on Cycle 1 Day 11. |
| OG008 | Phase 1 Food Effect and Rifampin DDI Sub-study: PF-06747775 + Rifampin | Participants were planned to receive continuous oral dosing of PF-06747775 at Recommended Phase 2 Dose (RP2D) QD for a 21-day cycles plus rifampin 600 mg QD through Day 10 to 21 of Cycle 1. No participants were enrolled or treated in this cohort prior to study termination. |
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| OG002 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG003 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
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| OG002 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
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| OG001 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). |
| OG002 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG003 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG004 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
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| OG002 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG003 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG004 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
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| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | Phase 2 Cohort 1: PF-06747775 200 mg QD | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycle (up to a maximum of 28 weeks). |
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| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | Phase 2 Cohort 1: PF-06747775 200 mg QD | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycle (up to a maximum of 28 weeks). |
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| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | Phase 2 Cohort 1: PF-06747775 200 mg QD | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycle (up to a maximum of 28 weeks). |
|
|
| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | Phase 2 Cohort 1: PF-06747775 200 mg QD | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycle (up to a maximum of 28 weeks). |
|
|
| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | Phase 2 Cohort 1: PF-06747775 200 mg QD | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycle (up to a maximum of 28 weeks). |
|
|
| Phase 1 Dose-escalation: PF-06747775 150 mg QD |
Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | Phase 2 Cohort 1: PF-06747775 200 mg QD | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycle (up to a maximum of 28 weeks). |
| OG008 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG009 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
|
|
| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | Phase 2 Cohort 1: PF-06747775 200 mg QD | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycle (up to a maximum of 28 weeks). |
| OG008 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG009 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
|
|
| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | Phase 2 Cohort 1: PF-06747775 200 mg QD | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycle (up to a maximum of 28 weeks). |
| OG008 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG009 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
|
|
| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | Phase 2 Cohort 1: PF-06747775 200 mg QD | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycle (up to a maximum of 28 weeks). |
| OG008 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG009 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
|
|
Participants received a single oral dose of PF-06747775 50 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 50 mg QD for 21-day cycles (up to a maximum of 72 weeks). |
| OG002 | Phase 1 Dose-escalation: PF-06747775 150 mg QD | Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks). |
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | Phase 2 Cohort 1: PF-06747775 200 mg QD | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycle (up to a maximum of 28 weeks). |
| OG008 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG009 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
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| Participants |
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| Participants |
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| Participants |
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| Units | Counts |
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| Participants |
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| Units | Counts |
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| Participants |
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| Units |
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| Counts |
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| Participants |
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| Units | Counts |
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| Participants |
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Participants received a single oral dose of PF-06747775 150 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 150 mg QD for 21-day cycles (up to a maximum of 54 weeks).
| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | PF-06747775 200 mg QD Group | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous oral dosing of PF-06747775 200 mg QD for 21-day cycles (up to a maximum of 165 weeks). PF-06747775 200 mg QD group was a combined group of PF-06747775 200 mg QD + sildenafil 25 mg SD (Phase 1 Sildenafil sub-study), PF-06747775 200 mg QD + esomeprazole/itraconazole (Phase 1 Esomeprazole/Itraconazole sub-study), Japan Lead-in cohort (LIC) and Phase 2 Cohort 1. |
| OG008 | Phase 1 Sildenafil Sub-study: PF-06747775 300 mg QD + Sildenafil 25 mg SD | Participants received a single oral dose of sildenafil 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 121 weeks) plus a single oral dose of sildenafil 25 mg on Cycle 1 Day 11. |
| OG009 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). |
| OG010 | Phase 1 Food Effect and Rifampin DDI Sub-study: PF-06747775 + Rifampin | Participants were planned to receive continuous oral dosing of PF-06747775 at Recommended Phase 2 Dose (RP2D) QD for a 21-day cycles plus rifampin 600 mg QD through Day 10 to 21 of Cycle 1. No participants were enrolled or treated in this cohort prior to study termination. |
| OG011 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG012 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG013 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
|
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| OG003 | Phase 1 Dose-escalation: PF-06747775 275 mg QD | Participants received a single oral dose of PF-06747775 275 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 275 mg QD for 21-day cycles (up to a maximum of 128 weeks). |
| OG004 | Phase 1 Dose-escalation: PF-06747775 300 mg QD | Participants received a single oral dose of PF-06747775 300 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 188 weeks). |
| OG005 | Phase 1 Dose-escalation: PF-06747775 450 mg QD | Participants received a single oral dose of PF-06747775 450 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 450 mg QD for 21-day cycles (up to a maximum of 195 weeks). |
| OG006 | Phase 1 Dose-escalation: PF-06747775 600 mg QD | Participants received a single oral dose of PF-06747775 600 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 600 mg QD for 21-day cycles (up to a maximum of 182 weeks). |
| OG007 | PF-06747775 200 mg QD Group | Participants received a single oral dose of PF-06747775 200 mg on Day -4 in lead-in period, followed by continuous oral dosing of PF-06747775 200 mg QD for 21-day cycles (up to a maximum of 165 weeks). PF-06747775 200 mg QD group was a combined group of PF-06747775 200 mg QD + sildenafil 25 mg SD (Phase 1 Sildenafil sub-study), PF-06747775 200 mg QD + esomeprazole/itraconazole (Phase 1 Esomeprazole/Itraconazole sub-study), Japan Lead-in cohort (LIC) and Phase 2 Cohort 1. |
| OG008 | Phase 1 Sildenafil Sub-study: PF-06747775 300 mg QD + Sildenafil 25 mg SD | Participants received a single oral dose of sildenafil 25 mg on Day -8 (+/- 3 days) in lead-in period, followed by continuous oral dosing of PF-06747775 300 mg QD for 21-day cycles (up to a maximum of 121 weeks) plus a single oral dose of sildenafil 25 mg on Cycle 1 Day 11. |
| OG009 | Phase 1b Cohort 2A: PF-06747775 200 mg QD + Palbociclib 100 mg QD | Participants received continuous oral dosing of PF-06747775 200 mg QD plus palbociclib 100 mg QD for 21-day cycles (up to a maximum of 102 weeks). |
| OG010 | Phase 1 Food Effect and Rifampin DDI Sub-study: PF-06747775 + Rifampin | Participants were planned to receive continuous oral dosing of PF-06747775 at Recommended Phase 2 Dose (RP2D) QD for a 21-day cycles plus rifampin 600 mg QD through Day 10 to 21 of Cycle 1. No participants were enrolled or treated in this cohort prior to study termination. |
| OG011 | Phase 2 Cohort 2B: PF-06747775 + Palbociclib | Participants were planned to receive continuous oral dosing of PF-06747775 QD and palbociclib QD at RP2D for 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG012 | Phase 2 Cohort 2B: PF-06747775 Single Agent | Participants were planned to received continuous oral dosing of PF-06747775 QD at RP2D for a 21-day cycles. No participants were enrolled or treated in this cohort prior to study termination. |
| OG013 | Phase 1b Cohort 3: PF-06747775 + Avelumab | Participants were planned to receive continuous oral dosing of PF-06747775 at RP2D QD for 28-day cycles plus intravenous dosing of avelumab 10 mg/kg every 2 weeks (Q2W) on Days 1 and 15 of each cycle. No participants were enrolled or treated in this cohort prior to study termination. |
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| Units | Counts |
|---|---|
| Participants |
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Japanese participants received a single dose of PF-06747775 100 mg on Day -7 in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycle (up to a maximum of 25 weeks).
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| Units | Counts |
|---|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Units |
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| Counts |
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| Participants |
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Japanese participants received a single dose of PF-06747775 100 mg on Day -7 in lead-in period, followed by continuous dosing of PF-06747775 200 mg QD for 21-day cycle (up to a maximum of 25 weeks).
|
|
| Positive |
|
| Uninformative |
|
| Not done |
|
| Positive |
|
| Uninformative |
|
| Not done |
|
| Positive |
|
| Uninformative |
|
| Not done |
|
| Positive |
|
| Uninformative |
|
| Not done |
|
| Positive |
|
| Uninformative |
|
| Not done |
|
| Positive |
|
| Uninformative |
|
| Not done |
|
| Positive |
|
| Uninformative |
|
| Positive |
|
| Uninformative |
|
| Positive |
|
| Uninformative |
|
| Positive |
|
| Uninformative |
|
| Positive |
|
| Uninformative |
|
| Positive |
|
| Uninformative |
|
| Positive |
|
| Uninformative |
|