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)

Completed · Phase 1

Conditions studied: Metastatic Colorectal Cancer

In brief

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).

Key facts

Study ID: NCT03374254
Run by: Merck Sharp & Dohme LLC
People needed: 116
Starts: 2018-02-16
Expected to finish: 2023-07-18
Last updated by the study team: 2024-11-21

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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
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
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:
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

You may not qualify if…

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 (systolic blood pressure [SBP] ≥150 mmHg or diastolic blood pressure [DBP] ≥100 mmHg) 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
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:
Has a history of, or current, retinal vein occlusion (RVO) or current risk factors for RVO
Has retinal degenerative disease

Where it is running

City of Hope National Medical Center ( Site 0102) — Duarte, California, United States
Anschutz Medical Campus, Anschutz Cancer Pavilion ( Site 0106) — Aurora, Colorado, United States
Yale Cancer Center ( Site 0108) — New Haven, Connecticut, United States
Moffitt Cancer Center ( Site 0111) — Tampa, Florida, United States
University of Chicago ( Site 0105) — Chicago, Illinois, United States
Rutgers Cancer Institute of New Jersey ( Site 0107) — New Brunswick, New Jersey, United States
UPMC Cancer Center/Hillman Cancer Center ( Site 0113) — Pittsburgh, Pennsylvania, United States
Baylor Scott and White ( Site 0110) — Temple, Texas, United States
Seattle Cancer Care Alliance ( Site 0104) — Seattle, Washington, United States
Northwest Medical Specialties, PLLC ( Site 0101) — Tacoma, Washington, United States
Cross Cancer Institute ( Site 0123) — Edmonton, Alberta, Canada
Princess Margaret Cancer Centre ( Site 0122) — Toronto, Ontario, Canada
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0124) — Montreal, Quebec, Canada
Jewish General Hospital ( Site 0121) — Montreal, Quebec, Canada

Full record on ClinicalTrials.gov

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