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The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of PF-06671008 in patients with advanced solid tumors with the potential to have P-cadherin expression. The study will then expand to look at the selected dose in patients with P-cadherin expressing TNBC, CRC or NSCLC.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-06671008 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-06671008 | Drug | Dose Escalation Phase - Part 1 |
| |
| PF-06671008 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) - Part 1 | DLT was defined as any of the following adverse events occurring in the first cycle of treatment (21 days after the first dose): a) Hematologic: Febrile neutropenia defined as an absolute neutrophil count (ANC) <1.0 x 10^9/L with a single temperature of >38.3°C, or 101°F, or a sustained temperature of >=38°C, or 100.4°F, for more than one hour; b) Non-hematologic: Delay by more than 2 weeks in receiving the next scheduled dose due to persisting treatment related toxicities; c) Any grade 3 or 4 clinically-relevant hematologic or non-hematologic toxicity. | Baseline through Day 21 (Cycle 1) |
| Number of Participants With Objective Response (OR) - Part 2 | Number of participants with OR based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. | Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Serum Concentration (Cmax) of PF-06671008 | Maximum serum concentration (Cmax) of PF-06671008 was observed directly from data. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values. | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
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Key Inclusion Criteria
Key Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memorial Sloan Kettering Cancer Center - Westchester | Harrison | New York | 10604 | United States | ||
| Memorial Sloan Kettering Cancer Center- Clinical Trials Office |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35493516 | Derived | Harding JJ, Garrido-Laguna I, Chen X, Basu C, Dowlati A, Forgie A, Hooper AT, Kamperschroer C, Max SI, Moreau A, Shannon M, Wong GY, Hong DS. A Phase 1 Dose-Escalation Study of PF-06671008, a Bispecific T-Cell-Engaging Therapy Targeting P-Cadherin in Patients With Advanced Solid Tumors. Front Immunol. 2022 Apr 14;13:845417. doi: 10.3389/fimmu.2022.845417. eCollection 2022. |
| Label | URL |
|---|---|
| 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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Twenty-eight (28) participants were enrolled and 27 participants received study drug. One participant discontinued before receiving treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | PF-06671008 1.5 ng/kg IV | PF-06671008 was administered as a weekly intravenous (IV) infusion in 21-day cycles at 1.5 nanogram/kilogram (ng/kg). PF-06671008 was administered for up to 4 cycles in this cohort. |
| FG001 | PF-06671008 7.5 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 7.5 ng/kg. PF-06671008 was administered for up to 3 cycles in this cohort. |
| FG002 | PF-06671008 20 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 20 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. |
| FG003 | PF-06671008 50 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 50 ng/kg. PF-06671008 was administered for up to 2 cycles in this cohort. |
| FG004 | PF-06671008 100 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 100 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. |
| FG005 | PF-06671008 200 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 200 ng/kg. PF-06671008 was administered for up to 16 cycles in this cohort. |
| FG006 | PF-06671008 300 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 300 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. |
| FG007 | PF-06671008 400 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 400 ng/kg. PF-06671008 was administered for up to 2 cycles in this cohort. |
| FG008 | PF-06671008 200 ng/kg SC | PF-06671008 was administered as a weekly subcutaneous (SC) injection in 21-day cycles at 200 ng/kg. PF-06671008 was administered for up to 5 cycles in this cohort. |
| FG009 | PF-06671008 200 ng/kg Prime and 300 ng/kg Maintenance IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at a priming dose of 200 ng/kg on Cycle 1 Day 1 (C1D1) and 300 ng/kg for all subsequent dosing. PF-06671008 was administered for up to 4 cycles in this cohort. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline analysis population included all participants treated (27)
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| ID | Title | Description |
|---|---|---|
| BG000 | PF-06671008 1.5 ng/kg IV | PF-06671008 was administered as a weekly intravenous (IV) infusion in 21-day cycles at 1.5 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. |
| BG001 | PF-06671008 7.5 ng/kg IV |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| 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) - Part 1 | DLT was defined as any of the following adverse events occurring in the first cycle of treatment (21 days after the first dose): a) Hematologic: Febrile neutropenia defined as an absolute neutrophil count (ANC) <1.0 x 10^9/L with a single temperature of >38.3°C, or 101°F, or a sustained temperature of >=38°C, or 100.4°F, for more than one hour; b) Non-hematologic: Delay by more than 2 weeks in receiving the next scheduled dose due to persisting treatment related toxicities; c) Any grade 3 or 4 clinically-relevant hematologic or non-hematologic toxicity. | All enrolled participants who received at least one dose of study intervention. | Posted | Count of Participants | Participants | Baseline through Day 21 (Cycle 1) |
|
For all Adverse Events: Start of treatment to and including 28 days after the last dose. For All-Cause Mortality: Start of treatment to and including 28 days after the last dose + follow-up period (up to 2 years)
The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PF-06671008 1.5 ng/kg IV | PF-06671008 was administered as a weekly intravenous (IV) infusion in 21-day cycles at 1.5 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 21.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 12, 2018 | Mar 20, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 17, 2018 | Mar 20, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D008175 | Lung Neoplasms |
| D001943 | Breast Neoplasms |
| D015179 | Colorectal Neoplasms |
| D064726 | Triple Negative Breast Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| C000705933 | PF-06671008 |
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| Drug |
Dose Expansion Phase - Part 2 |
|
| Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06671008 |
Time for Maximum serum concentration (Tmax) of PF-06671008 was observed directly from data as time of first occurrence. |
| C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
| Terminal Elimination Half-life (t1/2) of PF-06671008 | Terminal elimination half-life (t1/2) of PF-06671008 was calculated as ln(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. Arithmetic mean was not calculated if fewer than 3 participants had reportable parameter values. | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06671008 | Tau refers to the dosing interval, which was 1 week. Area under the concentration-time profile from time 0 to time tau (AUCtau) was determined using linear/log trapezoidal method. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values. | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
| Area Under the Curve From Time 0 Extrapolated to Infinity Time (AUCinf) of PF-06671008 | AUCinf was calculated as AUClast +(Clast*/kel), where AUClast is area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis, kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values. | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
| Systemic Clearance (CL) of PF-06671008 | Systemic Clearance (CL) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to IV arms. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values. | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
| Apparent Clearance (CL/F) of PF-06671008 | Apparent Clearance (CL/F) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to SC arm. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values. | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
| Number of Participants With OR - Part 1 | Number of participants with OR based on assessment of CR or PR according to RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. | Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression, unacceptable toxicity, or up to 24 months |
| Number of Participants With Progression Free Survival (PFS) - Part 2 | The period from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death"). | Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression or unacceptable toxicity, or up to 24 months |
| Number of Participants With Overall Survival (OS) - Part 2 | The period from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death). | Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression or unacceptable toxicity, or up to 24 months |
| Number of Participants With Anti Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06671008 | ADA against PF-06671008 in human serum samples was determined following a tiered approach using screening, confirmation, and titer/quantification by semi-quantitative enzyme linked immunosorbent assay (ELISA). Endpoint titer >=1.18 was considered positive. | C1D1 0 hrs, D15 0 hrs, and C2D1 0 hrs, and D1 0 hrs post additional dosings, up to 24 months |
| New York |
| New York |
| 10017 |
| United States |
| Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavillion | New York | New York | 10022 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| University Hospitals Cleveland Medical Center | Cleveland | Ohio | 44106 | United States |
| The University of Texas - M.D. Anderson Cancer Center | Houston | Texas | 77030 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Huntsman Cancer Hospital | Salt Lake City | Utah | 84112 | United States |
| Huntsman Cancer Institute | Salt Lake City | Utah | 84112 | United States |
| Withdrawal prior to treatment |
|
| Participant refused further follow-up |
|
| Death (follow-up phase) |
|
| Death (treatment phase) |
|
PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 7.5 ng/kg. PF-06671008 was administered for up to 3 cycles in this cohort.
| BG002 | PF-06671008 20 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 20 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. |
| BG003 | PF-06671008 50 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 50 ng/kg. PF-06671008 was administered for up to 2 cycles in this cohort. |
| BG004 | PF-06671008 100 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 100 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. |
| BG005 | PF-06671008 200 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 200 ng/kg. PF-06671008 was administered for up to 16 cycles in this cohort. |
| BG006 | PF-06671008 300 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 300 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. |
| BG007 | PF-06671008 400 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 400 ng/kg. PF-06671008 was administered for up to 2 cycles in this cohort. |
| BG008 | PF-06671008 200 ng/kg SC | PF-06671008 was administered as a weekly subcutaneous (SC) injection in 21-day cycles at 200 ng/kg. PF-06671008 was administered for up to 5 cycles in this cohort. |
| BG009 | PF-06671008 200 ng/kg Prime and 300 ng/kg Maintenance IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at a priming dose of 200 ng/kg on Cycle 1 Day 1 (C1D1) and 300 ng/kg for all subsequent dosing. PF-06671008 was administered for up to 4 cycles in this cohort. |
| BG010 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG001 | PF-06671008 7.5 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 7.5 ng/kg. PF-06671008 was administered for up to 3 cycles in this cohort. |
| OG002 | PF-06671008 20 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 20 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. |
| OG003 | PF-06671008 50 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 50 ng/kg. PF-06671008 was administered for up to 2 cycles in this cohort. |
| OG004 | PF-06671008 100 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 100 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. |
| OG005 | PF-06671008 200 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 200 ng/kg. PF-06671008 was administered for up to 16 cycles in this cohort. |
| OG006 | PF-06671008 300 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 300 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. |
| OG007 | PF-06671008 400 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 400 ng/kg. PF-06671008 was administered for up to 2 cycles in this cohort. |
| OG008 | PF-06671008 200 ng/kg SC | PF-06671008 was administered as a weekly subcutaneous (SC) injection in 21-day cycles at 200 ng/kg. PF-06671008 was administered for up to 5 cycles in this cohort. |
| OG009 | PF-06671008 200 ng/kg Prime and 300 ng/kg Maintenance IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at a priming dose of 200 ng/kg on Cycle 1 Day 1 (C1D1) and 300 ng/kg for all subsequent dosing. PF-06671008 was administered for up to 4 cycles in this cohort. |
|
|
| Primary | Number of Participants With Objective Response (OR) - Part 2 | Number of participants with OR based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. | This study was terminated early and Part 2 was not initiated. Data for this outcome measure was not collected. | Posted | Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months |
|
|
| Secondary | Maximum Serum Concentration (Cmax) of PF-06671008 | Maximum serum concentration (Cmax) of PF-06671008 was observed directly from data. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values. | All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/milliliter (ng/mL) | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
|
|
|
| Secondary | Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06671008 | Time for Maximum serum concentration (Tmax) of PF-06671008 was observed directly from data as time of first occurrence. | All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. | Posted | Median | Full Range | hours | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
|
|
|
| Secondary | Terminal Elimination Half-life (t1/2) of PF-06671008 | Terminal elimination half-life (t1/2) of PF-06671008 was calculated as ln(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. Arithmetic mean was not calculated if fewer than 3 participants had reportable parameter values. | All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. | Posted | Mean | Standard Deviation | hours | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
|
|
|
| Secondary | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06671008 | Tau refers to the dosing interval, which was 1 week. Area under the concentration-time profile from time 0 to time tau (AUCtau) was determined using linear/log trapezoidal method. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values. | All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram.hour/milliliter (ng.hr/mL) | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
|
|
|
| Secondary | Area Under the Curve From Time 0 Extrapolated to Infinity Time (AUCinf) of PF-06671008 | AUCinf was calculated as AUClast +(Clast*/kel), where AUClast is area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis, kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values. | All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hr/mL | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
|
|
|
| Secondary | Systemic Clearance (CL) of PF-06671008 | Systemic Clearance (CL) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to IV arms. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values. | All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | milliliter/hour/kilogram (mL/hr/kg) | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
|
|
|
| Secondary | Apparent Clearance (CL/F) of PF-06671008 | Apparent Clearance (CL/F) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to SC arm. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values. | All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/hr/kg | C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose |
|
|
|
| Secondary | Number of Participants With OR - Part 1 | Number of participants with OR based on assessment of CR or PR according to RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. | All randomized participants who received at least 1 dose of study intervention, had measurable disease baseline assessment and at least 1 post baseline assessment or disease progression or death before the first tumor assessment. No participants met the criteria of OR. | Posted | Count of Participants | Participants | Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression, unacceptable toxicity, or up to 24 months |
|
|
|
| Secondary | Number of Participants With Progression Free Survival (PFS) - Part 2 | The period from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death"). | This study was terminated early and Part 2 was not initiated. Data for this outcome measure were not collected. | Posted | Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression or unacceptable toxicity, or up to 24 months |
|
|
| Secondary | Number of Participants With Overall Survival (OS) - Part 2 | The period from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death). | This study was terminated early and Part 2 was not initiated. Data for this outcome measure were not collected. | Posted | Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression or unacceptable toxicity, or up to 24 months |
|
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| Secondary | Number of Participants With Anti Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06671008 | ADA against PF-06671008 in human serum samples was determined following a tiered approach using screening, confirmation, and titer/quantification by semi-quantitative enzyme linked immunosorbent assay (ELISA). Endpoint titer >=1.18 was considered positive. | All enrolled participants who received at least one dose of study intervention and had at least one post dose ADA sample analyzed. | Posted | Count of Participants | Participants | C1D1 0 hrs, D15 0 hrs, and C2D1 0 hrs, and D1 0 hrs post additional dosings, up to 24 months |
|
|
|
| 1 |
| 1 |
| 0 |
| 1 |
| 1 |
| 1 |
| EG001 | PF-06671008 7.5 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 7.5 ng/kg. PF-06671008 was administered for up to 3 cycles in this cohort. | 2 | 2 | 1 | 2 | 2 | 2 |
| EG002 | PF-06671008 20 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 20 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. | 1 | 3 | 1 | 3 | 3 | 3 |
| EG003 | PF-06671008 50 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 50 ng/kg. PF-06671008 was administered for up to 2 cycles in this cohort. | 1 | 2 | 2 | 2 | 2 | 2 |
| EG004 | PF-06671008 100 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 100 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. | 4 | 4 | 4 | 4 | 4 | 4 |
| EG005 | PF-06671008 200 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 200 ng/kg. PF-06671008 was administered for up to 16 cycles in this cohort. | 2 | 5 | 4 | 5 | 5 | 5 |
| EG006 | PF-06671008 300 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 300 ng/kg. PF-06671008 was administered for up to 4 cycles in this cohort. | 1 | 4 | 3 | 4 | 4 | 4 |
| EG007 | PF-06671008 400 ng/kg IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at 400 ng/kg. PF-06671008 was administered for up to 2 cycles in this cohort. | 3 | 3 | 2 | 3 | 3 | 3 |
| EG008 | PF-06671008 200 ng/kg SC | PF-06671008 was administered as a weekly subcutaneous (SC) injection in 21-day cycles at 200 ng/kg. PF-06671008 was administered for up to 5 cycles in this cohort. | 1 | 2 | 0 | 2 | 2 | 2 |
| EG009 | PF-06671008 200 ng/kg Prime and 300 ng/kg Maintenance IV | PF-06671008 was administered as a weekly IV infusion in 21-day cycles at a priming dose of 200 ng/kg on Cycle 1 Day 1 (C1D1) and 300 ng/kg for all subsequent dosing. PF-06671008 was administered for up to 4 cycles in this cohort. | 0 | 1 | 0 | 1 | 1 | 1 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Cytokine release syndrome | Immune system disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Non-systematic Assessment |
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| Rectal adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Non-systematic Assessment |
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| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Sinus arrhythmia | Cardiac disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Ventricular arrhythmia | Cardiac disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Tinnitus | Ear and labyrinth disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Periorbital oedema | Eye disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Aphthous ulcer | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Pancreatitis | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Infusion site extravasation | General disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Nodule | General disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Pain | General disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Cytokine release syndrome | Immune system disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
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| Ear infection | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
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| Lung infection | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
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| Mucosal infection | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
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| Oral candidiasis | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
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| Rash pustular | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
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| Soft tissue infection | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 21.1 | Non-systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 21.1 | Non-systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 21.1 | Non-systematic Assessment |
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| Amylase increased | Investigations | MedDRA 21.1 | Non-systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 21.1 | Non-systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA 21.1 | Non-systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 21.1 | Non-systematic Assessment |
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| Electrocardiogram QT prolonged | Investigations | MedDRA 21.1 | Non-systematic Assessment |
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| Lipase increased | Investigations | MedDRA 21.1 | Non-systematic Assessment |
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| Lymphocyte count decreased | Investigations | MedDRA 21.1 | Non-systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA 21.1 | Non-systematic Assessment |
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| Weight decreased | Investigations | MedDRA 21.1 | Non-systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 21.1 | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Restlessness | Psychiatric disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Urinary tract pain | Renal and urinary disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Vaginal discharge | Reproductive system and breast disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Embolism | Vascular disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 21.1 | Non-systematic Assessment |
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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.
| D012140 |
| Respiratory Tract Diseases |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
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| Cycle 2 Day 1 |
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| Cycle 2 Day 1 |
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| Cycle 2 Day 1 |
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| Cycle 2 Day 1 |
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| Cycle 2 Day 1 |
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| Cycle 2 Day 1 |
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| NAb |
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