Study of Pembrolizumab (MK-3475) vs Standard Therapy in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (MK-3475-177/KEYNOTE-177)

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

307 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2023-07-17

Brief Summary

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In this study, participants with stage IV Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) colorectal carcinoma (CRC) will be randomly assigned to receive either pembrolizumab or the Investigator's choice of 1 of 6 standard of care (SOC) chemotherapy regimens for the treatment of advanced colorectal carcinoma. The primary study hypothesis is that pembrolizumab will prolong progression-free survival (PFS) or overall survival (OS) compared to current SOC chemotherapy.

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Detailed Description

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Conditions

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Colorectal Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pembrolizumab

Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Participants that have stopped the initial course of pembrolizumab and have stable disease but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 year additional).

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

IV infusion

Standard of Care (SOC)

Participants receive 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m\^2 IV over 2 hours then 250 mg/m\^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m\^2 IV over 2 hours then 250 mg/m\^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Participants that have stopped pembrolizumab and have stable disease but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 year additional).

Group Type ACTIVE_COMPARATOR

mFOLFOX6

Intervention Type DRUG

Regimen consists of oxaliplatin 85 mg/m\^2 IV on Day 1, leucovorin 400 mg/m\^2 or levoleucovorin 200 mg/m\^2 IV on Day 1, 5-fluorouracil (5-FU) 400 mg/m\^2 IV bolus on Day 1 and then 1200 mg/m\^2/day IV over 2 days for total dose of 2400 mg/m\^2 in each 2-week cycle

FOLFIRI

Intervention Type DRUG

Regimen consists of irinotecan 180 mg/m\^2 IV on Day 1, leucovorin 400 mg/m\^2 or levoleucovorin 200 mg/m\^2 IV on Day 1, 5-FU 400 mg/m\^2 IV bolus on Day 1 and then 1200 mg/m\^2/day IV over 2 days for total dose of 2400 mg/m\^2 in each 2-week cycle

Pembrolizumab

Intervention Type BIOLOGICAL

IV infusion

Bevacizumab

Intervention Type BIOLOGICAL

IV infusion

Cetuximab

Intervention Type BIOLOGICAL

IV infusion

Interventions

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mFOLFOX6

Regimen consists of oxaliplatin 85 mg/m\^2 IV on Day 1, leucovorin 400 mg/m\^2 or levoleucovorin 200 mg/m\^2 IV on Day 1, 5-fluorouracil (5-FU) 400 mg/m\^2 IV bolus on Day 1 and then 1200 mg/m\^2/day IV over 2 days for total dose of 2400 mg/m\^2 in each 2-week cycle

Intervention Type DRUG

FOLFIRI

Regimen consists of irinotecan 180 mg/m\^2 IV on Day 1, leucovorin 400 mg/m\^2 or levoleucovorin 200 mg/m\^2 IV on Day 1, 5-FU 400 mg/m\^2 IV bolus on Day 1 and then 1200 mg/m\^2/day IV over 2 days for total dose of 2400 mg/m\^2 in each 2-week cycle

Intervention Type DRUG

Pembrolizumab

IV infusion

Intervention Type BIOLOGICAL

Bevacizumab

IV infusion

Intervention Type BIOLOGICAL

Cetuximab

IV infusion

Intervention Type BIOLOGICAL

Other Intervention Names

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MK-3475 SCH 900475 KEYTRUDA®

Eligibility Criteria

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Inclusion Criteria

* Locally confirmed dMMR or MSI-H stage IV colorectal carcinoma
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
* Life expectancy of at least 3 months
* Measurable disease
* Female participants of childbearing potential must be willing to use adequate contraception for the course of the study starting with the first dose of study medication through 180 days after the last dose of standard of care (SOC) therapy or 120 days after the last pembrolizumab dose
* Male participants must agree to use adequate contraception for the course of the study starting with the first dose of study medication through 180 days after the last dose of study medication for chemotherapy arm (no contraception requirement for pembrolizumab \[MK-3475\] arm)
* Adequate organ function

Exclusion Criteria

* Has received prior systemic therapy for Stage IV colorectal cancer. May have received prior adjuvant chemotherapy for colorectal cancer as long as it was completed at least 6 months prior to randomization on this study
* Currently participating and receiving treatment in another study, or participated in a study of an investigational agent and received treatment, or used an investigational device within 4 weeks of randomization
* Active autoimmune disease that has required systemic treatment in past 2 years
* Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization on this study
* Radiation therapy within 4 weeks prior to randomization on this study and not recovered to baseline from adverse events due to radiation therapy
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization on this study
* Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-programmed cell death \[PD\]-1, anti-PD ligand 1 \[L1\], anti-PD-L2 agent, or anti-cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\] agent, etc.)
* Another malignancy that is progressing or requires active treatment with the exception of non-melanomatous skin cancer that has undergone potentially curative therapy and in situ cervical carcinoma
* Received a live or a live attenuated vaccine within 30 days of planned start of study medication
* Known history of Human Immunodeficiency Virus (HIV), Hepatitis B or C
* Known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis
* Known history of active tuberculosis (Bacillus tuberculosis \[TB\])
* Active infection requiring systemic therapy
* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
* Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of SOC (for male and female participants) or 120 days after the last dose of pembrolizumab (for female participants only)

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No