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)

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 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).

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Biological: Pembrolizumab; Drug: Binimetinib; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-Fluorouracil [5-FU]; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute ( Site 0123)
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre ( Site 0122)
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0124)
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital ( Site 0121)
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center ( Site 0102)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Anschutz Medical Campus, Anschutz Cancer Pavilion ( Site 0106)
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center ( Site 0108)
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center ( Site 0111)
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago ( Site 0105)
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903-2681
      • Rutgers Cancer Institute of New Jersey ( Site 0107)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Center/Hillman Cancer Center ( Site 0113)
  • Texas
    • Temple, Texas, United States, 76508
      • Baylor Scott and White ( Site 0110)
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance ( Site 0104)
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties, PLLC ( Site 0101)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• 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

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 (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

  • 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A Part 1: Pembrolizumab +Binimetinib 30 mg; 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.	Biological: Pembrolizumab; 200 mg Pembrolizumab solution for IV infusion Q3W; Other Names: MK-3475; Drug: Binimetinib; tablet orally BID at 30 or 45 mg depending upon DLT profile; Other Names: MEK162, ARRY-162, ARRY-438162
Experimental: Cohort A Part 1: Pembrolizumab +Binimetinib 45 mg; 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.	Biological: Pembrolizumab; 200 mg Pembrolizumab solution for IV infusion Q3W; Other Names: MK-3475; Drug: Binimetinib; tablet orally BID at 30 or 45 mg depending upon DLT profile; Other Names: MEK162, ARRY-162, ARRY-438162
Experimental: Cohort B Part 1: Pembrolizumab + mFOLFOX7; 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.	Biological: Pembrolizumab; 200 mg Pembrolizumab solution for IV infusion Q3W; Other Names: MK-3475; Drug: Oxaliplatin; 85 mg/m^2 as IV infusion. Administered Q2W as part of mFOLFOX7 cocktail. Dose may be de-escalated to 70 mg/m^2 if the standard dose of mFOLFOX7 is deemed too toxic per mTPI, based upon occurrence of DLTs.; Drug: Leucovorin; 400 mg/m^2 as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation.; Other Names: calcium folinate; Drug: 5-Fluorouracil [5-FU]; 2400 mg/m^2 over 46-48 hours as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation. Dose may be de-escalated to 2000 mg/m^2 if the standard dose of mFOLFOX7 or FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.
Experimental: Cohort B Part 2: Pembrolizumab + mFOLFOX; 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.	Biological: Pembrolizumab; 200 mg Pembrolizumab solution for IV infusion Q3W; Other Names: MK-3475; Drug: Oxaliplatin; 85 mg/m^2 as IV infusion. Administered Q2W as part of mFOLFOX7 cocktail. Dose may be de-escalated to 70 mg/m^2 if the standard dose of mFOLFOX7 is deemed too toxic per mTPI, based upon occurrence of DLTs.; Drug: Leucovorin; 400 mg/m^2 as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation.; Other Names: calcium folinate; Drug: 5-Fluorouracil [5-FU]; 2400 mg/m^2 over 46-48 hours as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation. Dose may be de-escalated to 2000 mg/m^2 if the standard dose of mFOLFOX7 or FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.
Experimental: Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg; 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.	Biological: Pembrolizumab; 200 mg Pembrolizumab solution for IV infusion Q3W; Other Names: MK-3475; Drug: Binimetinib; tablet orally BID at 30 or 45 mg depending upon DLT profile; Other Names: MEK162, ARRY-162, ARRY-438162; Drug: Oxaliplatin; 85 mg/m^2 as IV infusion. Administered Q2W as part of mFOLFOX7 cocktail. Dose may be de-escalated to 70 mg/m^2 if the standard dose of mFOLFOX7 is deemed too toxic per mTPI, based upon occurrence of DLTs.; Drug: Leucovorin; 400 mg/m^2 as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation.; Other Names: calcium folinate; Drug: 5-Fluorouracil [5-FU]; 2400 mg/m^2 over 46-48 hours as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation. Dose may be de-escalated to 2000 mg/m^2 if the standard dose of mFOLFOX7 or FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.
Experimental: Cohort D Part 1: Pembrolizumab + FOLFIRI; 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.	Biological: Pembrolizumab; 200 mg Pembrolizumab solution for IV infusion Q3W; Other Names: MK-3475; Drug: Leucovorin; 400 mg/m^2 as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation.; Other Names: calcium folinate; Drug: 5-Fluorouracil [5-FU]; 2400 mg/m^2 over 46-48 hours as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation. Dose may be de-escalated to 2000 mg/m^2 if the standard dose of mFOLFOX7 or FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.; Drug: Irinotecan; 180 mg/m^2 as IV infusion. Administered Q2W as part of FOLFIRI cocktail. Dose may be de-escalated to 150 mg/m^2 if the standard dose of FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.
Experimental: Cohort D Part 2: Pembrolizumab + FOLFIRI; 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.	Biological: Pembrolizumab; 200 mg Pembrolizumab solution for IV infusion Q3W; Other Names: MK-3475; Drug: Leucovorin; 400 mg/m^2 as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation.; Other Names: calcium folinate; Drug: 5-Fluorouracil [5-FU]; 2400 mg/m^2 over 46-48 hours as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation. Dose may be de-escalated to 2000 mg/m^2 if the standard dose of mFOLFOX7 or FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.; Drug: Irinotecan; 180 mg/m^2 as IV infusion. Administered Q2W as part of FOLFIRI cocktail. Dose may be de-escalated to 150 mg/m^2 if the standard dose of FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.
Experimental: Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg; 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.	Biological: Pembrolizumab; 200 mg Pembrolizumab solution for IV infusion Q3W; Other Names: MK-3475; Drug: Binimetinib; tablet orally BID at 30 or 45 mg depending upon DLT profile; Other Names: MEK162, ARRY-162, ARRY-438162; Drug: Leucovorin; 400 mg/m^2 as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation.; Other Names: calcium folinate; Drug: 5-Fluorouracil [5-FU]; 2400 mg/m^2 over 46-48 hours as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation. Dose may be de-escalated to 2000 mg/m^2 if the standard dose of mFOLFOX7 or FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.; Drug: Irinotecan; 180 mg/m^2 as IV infusion. Administered Q2W as part of FOLFIRI cocktail. Dose may be de-escalated to 150 mg/m^2 if the standard dose of FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.
Experimental: Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg; 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.	Biological: Pembrolizumab; 200 mg Pembrolizumab solution for IV infusion Q3W; Other Names: MK-3475; Drug: Binimetinib; tablet orally BID at 30 or 45 mg depending upon DLT profile; Other Names: MEK162, ARRY-162, ARRY-438162; Drug: Leucovorin; 400 mg/m^2 as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation.; Other Names: calcium folinate; Drug: 5-Fluorouracil [5-FU]; 2400 mg/m^2 over 46-48 hours as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation. Dose may be de-escalated to 2000 mg/m^2 if the standard dose of mFOLFOX7 or FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.; Drug: Irinotecan; 180 mg/m^2 as IV infusion. Administered Q2W as part of FOLFIRI cocktail. Dose may be de-escalated to 150 mg/m^2 if the standard dose of FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT)	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).	Up to approximately first 28 days of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)	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.	Up to Approximately 64 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Array BioPharma
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Chen EX, Kavan P, Tehfe M, Kortmansky JS, Sawyer MB, Chiorean EG, Lieu CH, Polite B, Wong L, Fakih M, Spencer K, Chaves J, Li C, Leconte P, Adelberg D, Kim R. Pembrolizumab Plus Binimetinib With or Without Chemotherapy for MSS/pMMR Metastatic Colorectal Cancer: Outcomes From KEYNOTE-651 Cohorts A, C, and E. Clin Colorectal Cancer. 2024 Jun;23(2):183-193. doi: 10.1016/j.clcc.2024.03.002. Epub 2024 Apr 1.
• Kim R, Tehfe M, Kavan P, Chaves J, Kortmansky JS, Chen EX, Lieu CH, Wong L, Fakih M, Spencer K, Zhao Q, Predoiu R, Li C, Leconte P, Adelberg D, Chiorean EG. Pembrolizumab Plus mFOLFOX7 or FOLFIRI for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer: KEYNOTE-651 Cohorts B and D. Clin Colorectal Cancer. 2024 Jun;23(2):118-127.e6. doi: 10.1016/j.clcc.2024.03.001. Epub 2024 Apr 1.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2018
• Primary Completion (Actual): September 8, 2021
• Study Completion (Actual): July 18, 2023

Study Registration Dates

• First Submitted: December 12, 2017
• First Submitted That Met QC Criteria: December 12, 2017
• First Posted (Actual): December 15, 2017

Study Record Updates

• Last Update Posted (Actual): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 5, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: CRC, MSS, non-MSI-H, PD-1, anti-PD-1, anti PD-1, MEK, MEK inhibitor
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Micronutrients; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Protective Agents; Antidotes; Vitamin B Complex; Vitamins; Oxaliplatin; Irinotecan; Fluorouracil; Pembrolizumab; Leucovorin
• Other Study ID Numbers: 3475-651; MK-3475-651 (Other Identifier: Merck Sharp & Dohme LLC); KEYNOTE-651 (Other Identifier: Merck Sharp & Dohme LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No