Description:
In this study, participants with MSI-H or dMMR advanced colorectal carcinoma 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.
Title
- Brief Title: 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)
- Official Title: A Phase III Study of Pembrolizumab (MK-3475) vs. Chemotherapy in Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (KEYNOTE-177)
Clinical Trial IDs
- ORG STUDY ID:
3475-177
- SECONDARY ID:
2015-002024-89
- SECONDARY ID:
163238
- SECONDARY ID:
MK-3475-177
- SECONDARY ID:
KEYNOTE-177
- NCT ID:
NCT02563002
Conditions
Interventions
Drug | Synonyms | Arms |
---|
mFOLFOX6 | | Standard of Care |
FOLFIRI | | Standard of Care |
pembrolizumab | | Pembrolizumab |
bevacizumab | | Standard of Care |
cetuximab | | Standard of Care |
Purpose
In this study, participants with MSI-H or dMMR advanced colorectal carcinoma 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Pembrolizumab | Experimental | 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). | |
Standard of Care | Active Comparator | 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). | - mFOLFOX6
- FOLFIRI
- bevacizumab
- cetuximab
|
Eligibility Criteria
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 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 SOC therapy or 120 days after the last pembrolizumab dose
- 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 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 or 120 days after the last dose of pembrolizumab
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-free Survival (PFS) |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Overall Response Rate (ORR) |
Time Frame: | Up to 36 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Merck Sharp & Dohme Corp. |
Trial Keywords
Last Updated
March 12, 2021