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| ID | Type | Description | Link |
|---|---|---|---|
| C4211005 | Other Identifier | Pfizer |
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In the phase Ib, the primary purpose is to establish the maximum tolerated dose (MTD)(s)/recommended phase ll dose (RP2D) and schedule of LEE011 and MEK162 orally administered combination. Once the MTD(s)/RP2D have been determined for each tested schedule, additional patients will be enrolled in the phase II portion of the study at the RP2D on the chosen schedule in order to assess the anti-tumor activity of the combination in addition to continued evaluation of safety.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase Ib | Experimental | The phase Ib is the dose escalation part where successive cohorts of 3-6 newly enrolled patients receiving various dose pairs considering the recommendation from an adaptive BLRM incorporating the EWOC principle until MTD(s)/RP2D is defined. If multiple alternate dosing schedules are explored in parallel, the allocation of patients will proceed in an alternating fashion. Approximately 40 patients are expected to be treated during the phase Ib part of the study. Dosing Schedule 1: MEK162 administered orally twice daily on a continuous dosing schedule. LEE011 administered orally once daily for 21 days followed by a 1 week break (28-day cycle). Dosing Schedule 2: MEK162 administered orally twice daily and LEE011 administered orally once daily for 3 weeks followed by a 1 week break (28-day cycle). Dosing Schedule 3: MEK162 administered orally twice daily and LEE011 administered once daily for 2 weeks followed by a 1 week break (21-day cycle). |
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| Phase II | Experimental | The Phase II part will begin once the MTD(s)/RP2D have been determined in the Phase Ib in order to assess antitumor activity of the LEE011and MEK162 combination. Patients enrolled in the Phase II part of the study are required to have measurable disease. Approximately 40 patients will be treated in this part. Phase II part will begin at the RP2D on the chosen schedule in order to assess antitumor activity of the LEE011 and MEK162 combination. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LEE011 | Drug | LEE011 will be administered orally once daily |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Dose Limiting Toxicities (Phase Ib) | To estimate the maximum tolerate doses (MTDs) and/or identify the RP2D and schedule of LEE011 and MEK162 combination. A dose-limiting toxicity (DLT) was defined as an AE or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle of treatment with ribociclib and binimetinib. | first 28 days of treatment |
| Objective Response Rate (ORR) (Phase II) | ORR is the proportion of patients with best overall response of complete response (CR) or partial response (PR) by month 2 assessed according to RECIST 1.1 criteria. ORR is done to describe the anti-tumor activity of LEE011 and MEK162 combination. The primary analysis of the ORR was based on the Investigator's assessment of overall lesion responses per RECIST 1.1. | Approximately 12 months after the FPFV |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Concentration-time Profile (AUCtau) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | Cycle 1 Day 1 |
| Plasma Concentration-time Profile (AUCtau) of MEK162 (Phase Ib) |
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Inclusion Criteria:
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
Patients enrolled into phase Ib may be enrolled with evaluable disease only. Patients enrolled into the phase II expansion must have at least one measurable lesion as defined by RECIST 1.1 criteria for solid tumors.
Patients must have adequate organ function, as defined by the following parameter
Exclusion Criteria:
Presence of any brain metastases detected by MRI or CT with i.v. contrast of the brain at screening.
Uncontrolled arterial hypertension despite medical treatment
Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
Patients who are currently receiving treatment with agents that are known to cause QTc prolongation in humans.
Patients who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) or elevated baseline CK levels (≥ Grade 2)
Patients who are currently receiving treatment with agents that are metabolized predominantly through CYP3A4 and that have a narrow therapeutic window.
Patients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (i.e. uncontrolled diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection).
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
Other protocol related inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Dept of Oncology | San Francisco | California | 94101 | United States | ||
| California Pacific Medical Center Onc Dept |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35294522 | Derived | Schuler M, Zimmer L, Kim KB, Sosman JA, Ascierto PA, Postow MA, De Vos FYFL, van Herpen CML, Carlino MS, Johnson DB, Berking C, Reddy MB, Harney AS, Berlin JD, Amaria RN. Phase Ib/II Trial of Ribociclib in Combination with Binimetinib in Patients with NRAS-mutant Melanoma. Clin Cancer Res. 2022 Jul 15;28(14):3002-3010. doi: 10.1158/1078-0432.CCR-21-3872. |
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Screening details:
Screening assessments were performed within 14 days prior to the first dose of ribociclib and binimetinib except for the pretreatment tumor biopsy, which was performed within 28 days before dosing. A total of 23 patients were screened but not enrolled.
Upon study entry, all patients were required to provide either an archival tumor biopsy with the corresponding pathology report or a newly obtained tumor biopsy. Both parts of the study were limited to patients aged 18 or older with metastatic or locally advanced NRAS-mutant melanoma.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1b 28-Day Schedule | A combined total of 61 patients were treated in the 28-day (n=29) and 21-day (n=32) treatment cycles, and all patients discontinued treatment. The starting dose in the 28-day schedule was binimetinib 45 mg BID + ribociclib 200 mg QD. 28-Day Schedule: ribociclib was taken QD for 21 consecutive days followed by a 7-day planned break. Binimetinib was taken BID on a continuous dosing schedule. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| MEK162 45mg BID+LEE011 200mg |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | May 16, 2018 | Apr 27, 2020 |
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| MEK162 |
| Drug |
MEK162 will be administered orally twice daily |
|
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). |
| Cycle 1 Day 1 |
| Plasma Concentration-time Profile (AUCtau,ss) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| Plasma Concentration-time Profile (AUCtau,ss) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| Plasma Concentration-time Profile (Cmin,ss) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14 |
| Plasma Concentration-time Profile (Cmin,ss) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14 |
| Plasma Concentration-time Profile (Cmax) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | Cycle 1 Day 1 |
| Plasma Concentration-time Profile (Cmax) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | Cycle 1 Day 1 |
| Plasma Concentration-time Profile (Cmax,ss) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| Plasma Concentration-time Profile (Cmax,ss) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| Plasma Concentration-time Profile (Tmax) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | Cycle 1 Day 1 |
| Plasma Concentration-time Profile (Tmax) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | Cycle 1 Day 1 |
| Plasma Concentration-time Profile (Tmax,ss) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| Plasma Concentration-time Profile (Tmax,ss) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| Plasma Concentration-time Profile (T1/2,ss) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| Plasma Concentration-time Profile (T1/2,ss) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| Plasma Concentration-time Profile (CL/F) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | Cycle 1 Day 1 |
| Plasma Concentration-time Profile (CL/F) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | Cycle 1 Day 1 |
| Number of Participants With Adverse Drug Reactions | Safety and tolerability will be characterized through the incidence and severity of adverse drug reactions, serious adverse drug reactions, changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, dose reduction and dose intensity. | Approximately 12 months after FPFV |
| Duration of Response (DoR) - Phase 2 | To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. Please note: As clinicaltrials.gov only allows numerical data entry, the value of 999 indicates "not estimable" for confidence interval. | Approximately 12 months after the FPFV |
| Time to Progression (TTP) - Phase 2 | To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. | Approximately 12 months after the FPFV |
| Progression Free Survival (PFS) - Phase 1b and Phase 2 | To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. In the Phase 1b part, patients were combined for purposes of PFS analyses based on schedule received, since too few patients received any individual dose level to allow for valid PFS estimates within the respective dose levels. This is how the data were analyses and presented for the clinical study report. | Approximately 12 months after the FPFV |
| Overall Survival (OS) - Phase ll | To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. | Approximately 12 months after the FPFV |
| Best Overall Response (BOR) - Phase II | To assess clinical safety according to RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. | Approximately 12 months after the FPFV |
| San Francisco |
| California |
| 94120-7999 |
| United States |
| Karmanos Cancer Institute Dept of Oncology | Detroit | Michigan | 48201 | United States |
| Memorial Sloan Kettering Cancer Center Dept Oncology | New York | New York | 10021 | United States |
| Columbia University Medical Center- New York Presbyterian Onc Dept. | New York | New York | 10032 | United States |
| Vanderbilt University Medical Center SC - Dept of Oncology . | Nashville | Tennessee | 37232 | United States |
| University of Texas/MD Anderson Cancer Center Dept of Onc. | Houston | Texas | 77030-4009 | United States |
| Pfizer Investigative Site 1003 | North Sydney | New South Wales | 2060 | Australia |
| Pfizer Investigative Site 1002 | Westmead | New South Wales | 2145 | Australia |
| Pfizer Investigator Site 1001 | East Melbourne | Victoria | Australia |
| Pfizer Investigative Site 1050 | Essen | 45147 | Germany |
| Pfizer Investigative Site 1053 | Gera | 07548 | Germany |
| Pfizer Investigative Site 1052 | Hanover | 30625 | Germany |
| Pfizer Investigative Site 1051 | München | 80336 | Germany |
| Pfizer Investigative Site 1101 | Naples | 80131 | Italy |
| Pfizer Investigative Site 1151 | Utrecht | The Netherlands | 3508 GA | Netherlands |
| Pfizer Investigative Site 1150 | Nijmegen | 6525 GA | Netherlands |
| FG001 | Phase 1b 21-Day Schedule | A combined total of 61 patients were treated in the 28-day (n=29) and 21-day (n=32) treatment cycles, and all patients discontinued treatment. The starting dose in the 21-day schedule was binimetinib 30 mg BID + ribociclib 200 mg QD. 21-Day Schedule: ribociclib QD and binimetinib BID were taken QD for 14 consecutive days followed by a 7-day planned break. |
| FG002 | Phase 2 (Dose-expansion Phase) | The dose-expansion phase was initiated with a newly recruited group of patients. A total of 41 patients were treated, and all patients (100%) discontinued treatment. Based on the recommendations of the dose-escalation meetings between the Sponsor and the Investigators, the RP2D and schedule for the combination of binimetinib and ribociclib to be used for the dose-expansion phase of the study was binimetinib 45 mg BID + ribociclib 200 mg QD on the 28-day schedule. |
| COMPLETED |
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| NOT COMPLETED |
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| MEK162 45mg BID+LEE011 250mg |
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| MEK162 30mg BID+LEE011 300mg |
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| MEK162 45mg BID+LEE011 300mg |
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| MEK162 30mg LEE011 200mg |
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| MEK162 45mg LEE011 450mg |
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| MEK162 45mg LEE011 600mg |
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The baseline analysis population consists of the Full Analysis Set (FAS), which includes all patients who received at least 1 dose of ribociclib or binimetinib.
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | MEK162 45mg + LEE011 200mg |
| BG001 | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | MEK162 45mg+LEE011 250mg |
| BG002 | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| BG003 | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| BG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| BG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| BG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| BG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| BG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| BG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
| BG010 | Phase 2: MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| BG011 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Median | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Weight | Mean | Standard Deviation | kilograms |
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| Body mass index | Mean | Standard Deviation | (kg)/m^2 |
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| ECOG performance status | Count of Participants | Participants |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Number of Dose Limiting Toxicities (Phase Ib) | To estimate the maximum tolerate doses (MTDs) and/or identify the RP2D and schedule of LEE011 and MEK162 combination. A dose-limiting toxicity (DLT) was defined as an AE or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle of treatment with ribociclib and binimetinib. | Analysis is comprised of the dose-determining set, which is all patients from the safety set who either met the minimum exposure criterion below and had sufficient safety evaluations during Cycle 1 or discontinued earlier due to DLT during Cycle 1. | Posted | Number | occurrence | first 28 days of treatment |
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| Primary | Objective Response Rate (ORR) (Phase II) | ORR is the proportion of patients with best overall response of complete response (CR) or partial response (PR) by month 2 assessed according to RECIST 1.1 criteria. ORR is done to describe the anti-tumor activity of LEE011 and MEK162 combination. The primary analysis of the ORR was based on the Investigator's assessment of overall lesion responses per RECIST 1.1. | Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise. | Posted | Count of Participants | Participants | Approximately 12 months after the FPFV |
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| Secondary | Plasma Concentration-time Profile (AUCtau) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS) which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/ml | Cycle 1 Day 1 |
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| Secondary | Plasma Concentration-time Profile (AUCtau) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/ml | Cycle 1 Day 1 |
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| Secondary | Plasma Concentration-time Profile (AUCtau,ss) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
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| Secondary | Plasma Concentration-time Profile (AUCtau,ss) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
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| Secondary | Plasma Concentration-time Profile (Cmin,ss) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14 |
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| Secondary | Plasma Concentration-time Profile (Cmin,ss) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14 |
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| Secondary | Plasma Concentration-time Profile (Cmax) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 1 |
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| Secondary | Plasma Concentration-time Profile (Cmax) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 1 |
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| Secondary | Plasma Concentration-time Profile (Cmax,ss) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
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| Secondary | Plasma Concentration-time Profile (Cmax,ss) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
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| Secondary | Plasma Concentration-time Profile (Tmax) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Median | Full Range | h | Cycle 1 Day 1 |
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| Secondary | Plasma Concentration-time Profile (Tmax) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Median | Full Range | h | Cycle 1 Day 1 |
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| Secondary | Plasma Concentration-time Profile (Tmax,ss) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Median | Full Range | h | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
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| Secondary | Plasma Concentration-time Profile (Tmax,ss) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Median | Full Range | h | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
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| Secondary | Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | (hr*ng/mL) / (hr*ng/mL) | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | (hr*ng/mL) / (hr*ng/mL | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Plasma Concentration-time Profile (T1/2,ss) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | h | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Plasma Concentration-time Profile (T1/2,ss) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | h | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Plasma Concentration-time Profile (CL/F) of LEE011 (Phase Ib) | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Cycle 1 Day 1 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Plasma Concentration-time Profile (CL/F) of MEK162 (Phase Ib) | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). | Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Cycle 1 Day 1 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Adverse Drug Reactions | Safety and tolerability will be characterized through the incidence and severity of adverse drug reactions, serious adverse drug reactions, changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, dose reduction and dose intensity. | Analysis group consists of the safety set, which included all patients who received at least 1 dose of ribociclib or binimetinib and had at least 1 postbaseline safety assessment. | Posted | Count of Participants | Participants | Approximately 12 months after FPFV |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Duration of Response (DoR) - Phase 2 | To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. Please note: As clinicaltrials.gov only allows numerical data entry, the value of 999 indicates "not estimable" for confidence interval. | Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise. | Posted | Median | 95% Confidence Interval | months | Approximately 12 months after the FPFV |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Progression (TTP) - Phase 2 | To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. | Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise. | Posted | Median | 95% Confidence Interval | months | Approximately 12 months after the FPFV |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression Free Survival (PFS) - Phase 1b and Phase 2 | To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. In the Phase 1b part, patients were combined for purposes of PFS analyses based on schedule received, since too few patients received any individual dose level to allow for valid PFS estimates within the respective dose levels. This is how the data were analyses and presented for the clinical study report. | Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise. | Posted | Median | 95% Confidence Interval | months | Approximately 12 months after the FPFV |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) - Phase ll | To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. | Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise. | Posted | Median | 95% Confidence Interval | months | Approximately 12 months after the FPFV |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Best Overall Response (BOR) - Phase II | To assess clinical safety according to RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. | Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise. | Posted | Count of Participants | Participants | Approximately 12 months after the FPFV |
|
|
Adverse Events (AE) were collected during the study, which began in June 2013 and concluded February 2018. After signing of the informed consent until 30 days after study treatment discontinuation.
An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
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 1b - 28 Day MEK162 45mg+LEE011 200mg | MEK162 45mg BID+LEE011 200mg QD | 3 | 16 | 8 | 16 | 16 | 16 |
| EG001 | Phase 1b - 28 Day MEK162 45mg+LEE011 250mg | MEK162 45mg BID+LEE011 250mg QD | 0 | 3 | 2 | 3 | 3 | 3 |
| EG002 | Phase 1b - 28 Day MEK162 30mg+LEE011 300mg | MEK162 30mg BID+LEE011 300mg QD | 1 | 4 | 2 | 4 | 4 | 4 |
| EG003 | Phase 1b - 28 Day MEK162 45mg+LEE011 300mg | MEK162 45mg BID+LEE011 300mg QD | 1 | 6 | 4 | 6 | 6 | 6 |
| EG004 | Phase 1b - 21 Day MEK162 30mg+LEE011 200mg | MEK162 30mg BID+LEE011 200mg QD | 0 | 5 | 2 | 5 | 5 | 5 |
| EG005 | Phase 1b - 21 Day MEK162 45mg+LEE011 200mg | MEK162 45mg BID+LEE011 200mg QD | 1 | 6 | 3 | 6 | 6 | 6 |
| EG006 | Phase 1b - 21 Day MEK162 30mg+LEE011 300mg | MEK162 30mg BID+LEE011 300mg QD | 0 | 2 | 1 | 2 | 2 | 2 |
| EG007 | Phase 1b - 21 Day MEK162 45mg+LEE011 300mg | MEK162 45mg BID+LEE011 300mg QD | 0 | 4 | 3 | 4 | 4 | 4 |
| EG008 | Phase 1b - 21 Day MEK162 45mg+LEE011 450mg | MEK162 45mg BID+LEE011 450mg QD | 0 | 9 | 3 | 9 | 9 | 9 |
| EG009 | Phase 1b - 21 Day MEK162 45mg+LEE011 600mg | MEK162 45mg BID+LEE011 600mg QD | 1 | 6 | 2 | 6 | 6 | 6 |
| EG010 | Phase 2 - Dose Expansion Phase | The dose-expansion phase was initiated with a newly recruited group of patients. Binimetinib 45 mg BID + ribociclib 200 mg QD on 28-day schedule | 23 | 41 | 22 | 41 | 41 | 41 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Intracranial tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Pyrexia | Nervous system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Face oedema | General disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Blood creatine phosphokinase | Investigations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Neutrophil | Investigations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Chronic obstructive pulmonary | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Obstructive airways | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Slow speech | Nervous system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Hemiplegia | Nervous system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Retinal detachment | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Small intestinal | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Rectal obstruction | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Intestinal haemorrhage | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Subileus | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Chills | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Micturition frequency | Renal and urinary disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Hypervolaemia | Metabolism and nutrition disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Staphylococcal bacteraemia | Infections and infestations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA Version 19.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Oedema peripheral | General disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Aeaemia | Blood and lymphatic system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Gastroesophageal reflux disease | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Granulocytopenia | Blood and lymphatic system disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Cardio-respiratiory arrest | Cardiac disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Chorioretinopathy | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Retinal detachment | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Retinopathy | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Macular oedema | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Subretinal fluid | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Detachment of retinal pigment epithelium | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Chorioretinal disorder | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Periorbital oedema | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Retinal disorder | Eye disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Glossodynia | Gastrointestinal disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Face oedema | General disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| |
| Astenia | General disorders | MedDRA Version 19.0 | Non-systematic Assessment |
|
The terms and conditions of the sponsor's agreements with its investigators may vary. However, the sponsor does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e., data from all sites) in the clinical trials.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Pfizer | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Aug 26, 2015 | Apr 28, 2020 | Prot_001.pdf |
| ID | Term |
|---|---|
| C000589651 | ribociclib |
| C581313 | binimetinib |
Not provided
Not provided
Not provided
| Death |
|
| Progressive Disease |
|
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Other |
|
| 1-Restricted in physically strenuous activity |
|
| 2-Ambulatory and capable of all selfcare |
|
|
| Phase 1b 21-Day MEK162 30mg+LEE011 200mg |
MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| Phase 1b 21-Day MEK162 30mg+LEE011 200mg |
MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
MEK162 45mg+LEE011 300mg
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
MEK162 45mg+LEE011 300mg
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| Phase 1b 21-Day MEK162 30mg+LEE011 200mg |
MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| Phase 1b 21-Day MEK162 30mg+LEE011 200mg |
MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
MEK162 45mg+LEE011 300mg
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
MEK162 45mg+LEE011 300mg
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| Phase 1b 21-Day MEK162 30mg+LEE011 200mg |
MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| Phase 1b 21-Day MEK162 30mg+LEE011 200mg |
MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
|
|
| OG004 | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | MEK162 30mg+LEE011 200mg |
| OG005 | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
| OG006 | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | MEK162 30mg+LEE011 300mg |
| OG007 | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 300mg |
| OG008 | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 450mg |
| OG009 | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 600mg |
| OG010 | Phase 2: MEK162 45mg+LEE011 200mg | MEK162 45mg+LEE011 200mg |
|
|
|
|
| OG002 | Phase 2 (Dose-expansion Phase) | The dose-expansion phase was initiated with a newly recruited group of patients. A total of 41 patients were treated, and all patients (100%) discontinued treatment. Based on the recommendations of the dose-escalation meetings between the Sponsor and the Investigators, the RP2D and schedule for the combination of binimetinib and ribociclib to be used for the dose-expansion phase of the study was binimetinib 45 mg BID + ribociclib 200 mg QD on the 28-day schedule. |
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