Safety and Efficacy of Pembrolizumab (MK-3475) Plus Binimetinib Alone or Pembrolizumab Plus Chemotherapy With or Without Binimetinib in Metastatic Colorectal Cancer (mCRC) Participants (MK-3475-651/KEYNOTE-651)
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT03374254
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to determine safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) for the following combinations: pembrolizumab plus binimetinib (Cohort A), pembrolizumab plus mFOLFOX7 (oxaliplatin 85 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2) (Cohort B), pembrolizumab plus mFOLFOX7 and binimetinib (Cohort C), pembrolizumab plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\]400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) (Cohort D), and pembrolizumab plus FOLFIRI and binimetinib (Cohort E).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 116
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At least 18 years of age
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Has a histologically-confirmed, unresectable or metastatic (Stage IV American Joint Committee on Cancer [AJCC seventh edition]) colorectal cancer (CRC)
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Has a locally determined non microsatellite instability high/ proficient mismatch repair (non-MSI-H/pMMR) tumor status
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Has at least 1 radiologically measurable lesion as defined by RECIST 1.1
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Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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Has a life expectancy of at least 3 months
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Has the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption.
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Has adequate organ function
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Male participants must agree to use contraception during the treatment period and for ≥180 days, after the last dose of study treatment and refrain from donating sperm during this period. Male participants with pregnant partners must agree to use a condom
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Female participants eligible to participate if not pregnant, not breastfeeding, and is not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees to follow contraceptive guidance during the treatment period and for ≥180 days after the last dose of study treatment
- Participants for Cohort A:
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Has been previously treated with fluoropyrimidine, irinotecan, and oxaliplatin
- Participants for Cohorts B and C:
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Must not have received prior systemic chemotherapy for Stage IV CRC
- Participants for Cohorts D and E:
-
Must have been previously treated with 1 line of therapy including a fluoropyrimidine plus an oxaliplatin-based regimen
- Participants for Cohorts A, C, and E:
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Have a 12-lead electrocardiogram (ECG) and echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed by the investigator or other qualified person to evaluate cardiac function prior to enrollment in the study
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Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of MK-3475
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Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (prior to the first dose of study therapy, or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Gr 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
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Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
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Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
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Has a known hypersensitivity, intolerability or contraindication to any component of study treatment, including premedication
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Has any active infection requiring systemic therapy
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Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
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Has received prior therapy with compounds targeting programmed death (PD)-1, PD-L1, PD-L2, or a mitogen-activated protein kinase (MAPK) pathway inhibitor
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Has an autoimmune disease that has required systemic treatment in the past 2 years with use of disease modifying agents, corticosteroids, or immunosuppressive drugs
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Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization
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Has known history of human immunodeficiency virus (HIV) infection
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Has a known history of Hepatitis B
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Has received live vaccine within 30 days of the planned start of study therapy
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Has undergone major surgery and has not recovered adequately from any toxicity and/or complications from the intervention prior to starting study therapy
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Has baseline peripheral neuropathy/paresthesia
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Has any medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol, or complete the study.
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Has symptomatic congestive heart failure (CHF)
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Has a history of acute or chronic pancreatitis
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Has existing uncontrolled arterial hypertension (systolic blood pressure [SBP] ≥150 mmHg or diastolic blood pressure [DBP] ≥100 mmHg) despite appropriate medical therapy
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Has a history of thromboembolic or cerebrovascular events within 6 months prior to registration
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Has neuromuscular disorders associated with an elevated creatine kinase
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A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment
- Potential Participants for Cohorts A, C or E who are to Receive Binimetinib:
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Has a history of, or current, retinal vein occlusion (RVO) or current risk factors for RVO
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Has retinal degenerative disease
- Potential Participants for Cohorts A, C, D or E:
-
Has a known history of Gilbert's Syndrome
- Potential Participants for Cohorts D or E:
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Has a previous treatment with irinotecan
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Has plans to use, or is using, any herbal medications/supplements or any medications or foods that are strong inhibitors or inducers of cytochrome P450 3A 4/5 ≤1 week prior to the start of study treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg 5-Fluorouracil [5-FU] Participants in Cohort C will receive pembrolizumab 200 mg IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation. Cohort D Part 2: Pembrolizumab + FOLFIRI 5-Fluorouracil [5-FU] During Part 2, participants in Cohort D will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) until disease progression or discontinuation. Cohort B Part 1: Pembrolizumab + mFOLFOX7 5-Fluorouracil [5-FU] Participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W until disease progression or discontinuation. Cohort B Part 2: Pembrolizumab + mFOLFOX 5-Fluorouracil [5-FU] During Part 2, participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W until disease progression or discontinuation. Cohort D Part 1: Pembrolizumab + FOLFIRI 5-Fluorouracil [5-FU] Participants in Cohort D will receive a standard dose (DL1) of pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) IV Q2W until disease progression or discontinuation. Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg 5-Fluorouracil [5-FU] Participants in Cohort E will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation. Cohort A Part 1: Pembrolizumab +Binimetinib 30 mg Pembrolizumab Participants in Cohort A will receive pembrolizumab (200 mg) intravenous (IV) every 3 weeks (Q3W) plus binimetinib orally at of 30 mg twice a day (BID) until disease progression or discontinuation. Cohort A Part 1: Pembrolizumab +Binimetinib 30 mg Binimetinib Participants in Cohort A will receive pembrolizumab (200 mg) intravenous (IV) every 3 weeks (Q3W) plus binimetinib orally at of 30 mg twice a day (BID) until disease progression or discontinuation. Cohort A Part 1: Pembrolizumab +Binimetinib 45 mg Pembrolizumab Participants in Cohort A will receive pembrolizumab (200 mg) IV Q3W plus binimetinib orally at 45 mg BID (Dose Level 2 \[DL2\]) until disease progression or discontinuation. Cohort A Part 1: Pembrolizumab +Binimetinib 45 mg Binimetinib Participants in Cohort A will receive pembrolizumab (200 mg) IV Q3W plus binimetinib orally at 45 mg BID (Dose Level 2 \[DL2\]) until disease progression or discontinuation. Cohort B Part 1: Pembrolizumab + mFOLFOX7 Pembrolizumab Participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W until disease progression or discontinuation. Cohort B Part 1: Pembrolizumab + mFOLFOX7 Oxaliplatin Participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W until disease progression or discontinuation. Cohort B Part 1: Pembrolizumab + mFOLFOX7 Leucovorin Participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W until disease progression or discontinuation. Cohort B Part 2: Pembrolizumab + mFOLFOX Pembrolizumab During Part 2, participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W until disease progression or discontinuation. Cohort B Part 2: Pembrolizumab + mFOLFOX Oxaliplatin During Part 2, participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W until disease progression or discontinuation. Cohort B Part 2: Pembrolizumab + mFOLFOX Leucovorin During Part 2, participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W until disease progression or discontinuation. Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg Pembrolizumab Participants in Cohort C will receive pembrolizumab 200 mg IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation. Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg Binimetinib Participants in Cohort C will receive pembrolizumab 200 mg IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation. Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg Oxaliplatin Participants in Cohort C will receive pembrolizumab 200 mg IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation. Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg Leucovorin Participants in Cohort C will receive pembrolizumab 200 mg IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2 over 46-48 hours) IV Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation. Cohort D Part 1: Pembrolizumab + FOLFIRI Pembrolizumab Participants in Cohort D will receive a standard dose (DL1) of pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) IV Q2W until disease progression or discontinuation. Cohort D Part 1: Pembrolizumab + FOLFIRI Leucovorin Participants in Cohort D will receive a standard dose (DL1) of pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) IV Q2W until disease progression or discontinuation. Cohort D Part 1: Pembrolizumab + FOLFIRI Irinotecan Participants in Cohort D will receive a standard dose (DL1) of pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) IV Q2W until disease progression or discontinuation. Cohort D Part 2: Pembrolizumab + FOLFIRI Pembrolizumab During Part 2, participants in Cohort D will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) until disease progression or discontinuation. Cohort D Part 2: Pembrolizumab + FOLFIRI Leucovorin During Part 2, participants in Cohort D will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) until disease progression or discontinuation. Cohort D Part 2: Pembrolizumab + FOLFIRI Irinotecan During Part 2, participants in Cohort D will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) until disease progression or discontinuation. Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg Pembrolizumab Participants in Cohort E will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation. Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg Binimetinib Participants in Cohort E will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation. Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg Leucovorin Participants in Cohort E will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation. Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg Irinotecan Participants in Cohort E will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation. Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg Pembrolizumab During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort A During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg Binimetinib During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort A During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg Leucovorin During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort A During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg 5-Fluorouracil [5-FU] During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort A During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg Irinotecan During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort A During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT) Up to approximately first 28 days of treatment The occurrence of any of the following toxicities during Part 1 of the study (the first 21 days for Cohort A, first 28 days for Cohorts B,C, D, \& E), if possibly, probably or definitely related to study treatment, was considered a DLT:
Grade (Gr) 4 non hematologic toxicity, Gr 4 hematologic toxicity lasting \>7 days, Gr 3 thrombocytopenia, Any non-hematologic AE ≥Gr 3 in severity, Any Gr 3 or Gr 4 non-hematologic laboratory value, Febrile neutropenia Gr 3 or Gr 4, Any prolonged delay in initiating study therapy due to a treatment-related AE that started during the DLT period, Any treatment-related toxicity that causes the participant to discontinue treatment during the DLT period, Missing \>25% of binimetinib doses as a result of drug-related AE(s), Gr 5 toxicity, Cardiac disorders and vascular disorders, Eye disorders (Retinopathy or retinal detachment Gr ≥ 3).
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) Up to Approximately 64 months ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). The percentage of participants who experienced CR or PR is presented. Per Protocol, analysis was per cohort.
Trial Locations
- Locations (14)
Seattle Cancer Care Alliance ( Site 0104)
🇺🇸Seattle, Washington, United States
Rutgers Cancer Institute of New Jersey ( Site 0107)
🇺🇸New Brunswick, New Jersey, United States
Princess Margaret Cancer Centre ( Site 0122)
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0124)
🇨🇦Montreal, Quebec, Canada
Yale Cancer Center ( Site 0108)
🇺🇸New Haven, Connecticut, United States
Cross Cancer Institute ( Site 0123)
🇨🇦Edmonton, Alberta, Canada
Anschutz Medical Campus, Anschutz Cancer Pavilion ( Site 0106)
🇺🇸Aurora, Colorado, United States
Moffitt Cancer Center ( Site 0111)
🇺🇸Tampa, Florida, United States
City of Hope National Medical Center ( Site 0102)
🇺🇸Duarte, California, United States
University of Chicago ( Site 0105)
🇺🇸Chicago, Illinois, United States
Baylor Scott and White ( Site 0110)
🇺🇸Temple, Texas, United States
UPMC Cancer Center/Hillman Cancer Center ( Site 0113)
🇺🇸Pittsburgh, Pennsylvania, United States
Northwest Medical Specialties, PLLC ( Site 0101)
🇺🇸Tacoma, Washington, United States
Jewish General Hospital ( Site 0121)
🇨🇦Montreal, Quebec, Canada