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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Pembrolizumab — BIOLOGICAL
  200 mg Pembrolizumab solution for IV infusion Q3W
• Binimetinib — DRUG
  tablet orally BID at 30 or 45 mg depending upon DLT profile
• Oxaliplatin — DRUG
  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.
• Leucovorin — DRUG
  400 mg/m\^2 as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation.
• 5-Fluorouracil [5-FU] — DRUG
  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.
• Irinotecan — DRUG
  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.

Study Details

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 Dates

Start date

Feb 16, 2018

Status verified

Nov 2024

Primary completion

Sep 8, 2021

Completion

Jul 18, 2023

Study Design

Enrollment

116 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Primary Outcome Measure

Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT) [ Time Frame: Up to approximately first 28 days of treatment ]

Locations (10)

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