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Clinical Trial 19384

Cancer Type: Gastrointestinal Tumor
Interventions:Binimetinib; FOLFIRI; FOLFOX; Pembrolizumab (Keytruda)

Study Type: Treatment
Phase of Study: Phase I

  • Richard Kim

Call 813-745-6100
or 1-800-679-0775

Study Title

A Phase 1b Multi-cohort Study of the Combination of Pembrolizumab (MK-3475) plus Binimetinib alone or the Combination of Pembrolizumab plus Chemotherapy with or without Binimetinib in Participants with Metastatic Colorectal Cancer (KEYNOTE-651)


The purpose of this study is to test the safety of the study drugs, pembrolizumab with Binimetinib alone or in combination with standard of care chemotherapies to see how well the drugs work together and to see how the body handles the drug combinations to help determine the right dose.


Primary Objectives: To determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) for the following cohorts: Cohort A (pembrolizumab in combination with binimetinib in mCRC participants previously treated with fluoropyrimidine,irinotecan, and oxaliplatin). Cohort B (pembrolizumab in combination with mFOLFOX7 in previously untreated mCRC participants). Cohort C (pembrolizumab in combination with mFOLFOX7 and binimetinib in previously untreated mCRC participants). Cohort D (pembrolizumab in combination with FOLFIRI in mCRC participants previously treated with one line of a fluoropyrimidine plus oxaliplatin based therapy. Cohort E (pembrolizumab in combination with FOLFIRI and binimetinib in mCRC participants previously treated with one line of fluoropyrimidine plus oxaliplatin based regimen).

Inclusion Criteria

  • At least 18 years of age
  • Has a histologically-confirmed, unresectable or metastatic (Stage IV American Joint Committee on Cancer [AJCC seventh edition]) colorectal cancer (CRC)
  • Has a locally determined non microsatellite instability high/ proficient mismatch repair (non-MSI-H/pMMR) tumor status
  • Has at least 1 radiologically measurable lesion as defined by RECIST 1.1
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Has a life expectancy of at least 3 months
  • Has the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption.
  • Has adequate organ function
  • Must follow contraception guidelines
  • Not pregnant or breastfeeding
  • Participants for Cohort A: Has been previously treated with fluoropyrimidine, irinotecan, and oxaliplatin
  • Participants for Cohorts B and C: 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: 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

  • Exclusion Criteria

  • 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
  • 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
  • Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
  • Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has a known hypersensitivity, intolerability or contraindication to any component of study treatment, including premedication
  • Has any active infection requiring systemic therapy
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Has received prior therapy with compounds targeting programmed death (PD)-1, PD-L1, PD-L2, or a mitogen-activated protein kinase (MAPK) pathway inhibitor
  • Has an autoimmune disease that has required systemic treatment in the past 2 years with use of disease modifying agents, corticosteroids, or immunosuppressive drugs
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization
  • Has known history of human immunodeficiency virus (HIV) infection
  • Has a known history of Hepatitis B
  • Has received live vaccine within 30 days of the planned start of study therapy
  • Has undergone major surgery and has not recovered adequately from any toxicity and/or complications from the intervention prior to starting study therapy
  • Has baseline peripheral neuropathy/paresthesia
  • 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.
  • Has symptomatic congestive heart failure (CHF)
  • Has a history of acute or chronic pancreatitis
  • Has existing uncontrolled arterial hypertension despite appropriate medical therapy
  • Has a history of thromboembolic or cerebrovascular events within 6 months prior to registration
  • Has neuromuscular disorders associated with an elevated creatine kinase
  • Potential Participants for Cohorts A, C or E who are to Receive Binimetinib: Has a history of, or current, retinal vein occlusion (RVO) or current risk factors for RVO. 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: Has a previous treatment with irinotecan
  • 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