Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Chinese Participants With Stage IV Colorectal Cancer (MK-3475-C66)

NCT05239741 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: 3475-C66MK-3475-C66
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 32

Brief Summary

In this study, Chinese participants with MSI-H or dMMR advanced colorectal cancer will be assigned to receive either pembrolizumab or the Investigator's choice of 1 of 6 standard of care (SOC) chemotherapy regimens for treatment. There is no hypothesis testing for this study.

Conditions

Colorectal Neoplasms

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) For All Participants

  PFS is defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by BICR will be reported for all participants.

  Up to approximately 77 months

• Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) For RAS Wild-type Participants

  PFS is defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by BICR will be reported for RAS wild-type participants .

  Up to approximately 77 months

Secondary Outcomes (6)

• Overall Survival (OS) For All Participants

  Up to approximately 77 months

• Overall Survival (OS) For RAS Wild-type Participants

  Up to approximately 77 months

• Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) For All Participants

  Up to approximately 77 months

• Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) For RAS Wild-type Participants

  Up to approximately 77 months

• Number of Participants Who Experience at Least One Adverse Event (AE)

  Up to approximately 77 months

Study Arms (2)

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).

Biological: Pembrolizumab

Standard of Care Chemotherapy

ACTIVE COMPARATOR

Participants receive 1 of 6 possible standard chemotherapy regimens at the discretion of the investigator: (1) mFOLFOX6; (2) mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 14-day cycle (Q2W); (3) mFOLFOX6+cetuximab 400 mg/m\^2 IV over 2 hours then 250 mg/m\^2 over 1 hour weekly Q2W; (4) FOLFIRI; (5) FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 Q2W; OR (6) FOLFIRI+cetuximab 400 mg/m\^2 IV over 2 hours then 250 mg/m\^2 over 1 hour weekly Q2W. Participants with documented disease progression following chemotherapy can receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years).

Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-fluorouracil; Drug: Irinotecan; Biological: Bevacizumab; Biological: Cetuximab

Interventions

Pembrolizumab BIOLOGICAL

Intravenous (IV) infusion

Also known as: KEYTRUDA®, MK-3475

Pembrolizumab

Oxaliplatin DRUG

85 mg/m\^2 given as an intravenous infusion (IV) on Day 1 in each 14-day cycle (Q2W) as part of the mFOLFOX6 regimen

Standard of Care Chemotherapy

Leucovorin DRUG

400 mg/m\^2 given as an IV on Day 1 Q2W as part of the mFOLFOX6 and FOLFIRI regimens

Standard of Care Chemotherapy

5-fluorouracil DRUG

400 mg/m\^2 given as an IV bolus on Day 1 and then 1200 mg/m\^2/day IV over 2 days for a total dose of 2400 mg/m\^2 Q2W as part of the mFOLFOX6 and FOLFIRI regimens

Also known as: 5-FU

Standard of Care Chemotherapy

Irinotecan DRUG

180 mg/m\^2 IV on Day 1 Q2W as part of the FOLFIRI regimen

Standard of Care Chemotherapy

Bevacizumab BIOLOGICAL

IV infusion

Standard of Care Chemotherapy

Cetuximab BIOLOGICAL

IV infusion

Standard of Care Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Has a histologically confirmed diagnosis of colorectal adenocarcinoma that is at stage IV (as defined by American Joint Committee on Cancer eighth edition) \[National Comprehensive Cancer Network 2018\]
• Has centrally confirmed Microsatellite Instability-High/Mismatch Repair Deficient (MSI-H/dMMR) status
• Has centrally confirmed RAS and BRAF mutation status
• A woman of child-bearing potential (WOCBP) must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention.
• Has measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by the local site investigator/radiology
• Must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days before randomization
• Has a life expectancy of at least 3 months
• Has received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable hepatitis B virus (HBV) viral load prior to randomization if hepatitis B surface antigen (HBsAg) positive
• Has an undetectable Hepatitis C Virus (HCV) viral load if HCV infected
• Has well controlled Human Immunodeficiency Virus (HIV) on antiretroviral therapy (ART) if HIV infected
• Has received prior systemic therapy for stage IV colorectal cancer (CRC). Participants may have received prior adjuvant/neoadjuvant chemotherapy for CRC as long as it was completed at least 6 months prior to randomization
• Has undergone major operation within 4 weeks of randomization or has not adequately recovered from major surgery or has ongoing surgical complications
• Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], tumor necrosis factor receptor superfamily, member 4 \[OX 40\], tumor necrosis factor receptor superfamily member 9 \[CD137\])
• Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities, requiring corticosteroids

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (32)

Beijing Cancer hospital-Digestive Oncology ( Site 0001)

Beijing, Beijing Municipality, 100142, China

Location

Beijing Peking Union Medical College Hospital-Medical Oncology ( Site 0011)

Beijing, Beijing Municipality, 100730, China

Location

Tianjin Medical University Cancer Institute and Hospital-Gastric oncology ( Site 0019)

Tianjin, Beijing Municipality, China

Location

The First Affiliated Hospital of Chongqing Medical University ( Site 0051)

Chongqing, Chongqing Municipality, 400016, China

Location

Chongqing University Cancer Hospital-Medical Oncology ( Site 0012)

Chongqing, Chongqing Municipality, 400030, China

Location

Fujian Provincial Cancer Hospital ( Site 0009)

Fuzhou, Fujian, 350014, China

Location

Sun Yat-sen University Cancer Center ( Site 0047)

Guangzhou, Guangdong, 510060, China

Location

Guangdong Provincial People's Hospital ( Site 0035)

Guangzhou, Guangdong, 510080, China

Location

The First Affiliated Hospital, Sun Yat-sen University ( Site 0014)

Guangzhou, Guangdong, 510080, China

Location

The Sixth Affiliated Hospital of Sun Yat-sen University-Oncology ( Site 0048)

Guangzhou, Guangdong, 510655, China

Location

Cancer Hospital of Shantou University Medical College ( Site 0036)

Shantou, Guangdong, 515041, China

Location

Guangxi Medical University Affiliated Tumor Hospital ( Site 0039)

Nanning, Guangxi, 530200, China

Location

Harbin Medical University Cancer Hospital ( Site 0007)

Harbin, Heilongjiang, 150081, China

Location

Henan Cancer Hospital-henan cancer hospital ( Site 0015)

Zhengzhou, Henan, 450000, China

Location

Tongji Hospital Tongji Medical,Science & Technology-oncology ( Site 0018)

Wuhan, Hubei, 430000, China

Location

Wuhan Union Hospital Cancer Center-Cancer Center ( Site 0008)

Wuhan, Hubei, 430022, China

Location

The Third Xiangya Hospital of Central South University ( Site 0031)

Changsha, Hunan, 410013, China

Location

The Affiliated Jiangyin Hospital of Southeast University Medical College ( Site 0037)

Jiangyin, Jiangsu, 214400, China

Location

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Oncology ( Site 0002)

Nanjing, Jiangsu, 210008, China

Location

The first affiliated hospital of China medical university ( Site 0043)

Shemyang, Liaoning, 110001, China

Location

Tangdu Hospital of Fourth Military Medical University of Chi-General Surgery ( Site 0045)

Xi'an, Shaanxi, 710038, China

Location

Jinan Central Hospital-oncology department ( Site 0021)

Jinan, Shandong, 250013, China

Location

Shandong Cancer Hospital ( Site 0041)

Jinan, Shandong, 250117, China

Location

Shanghai Changhai Hospital ( Site 0024)

Shanghai, Shanghai Municipality, 200433, China

Location

Shanghai East Hospital ( Site 0022)

Shanghai, Shanghai Municipality, 201200, China

Location

Fudan University Shanghai Cancer Center-Oncology ( Site 0046)

Shanghai, Shanghai Municipality, 201321, China

Location

Shanxi Cancer Hospital ( Site 0032)

Taiyuan, Shanxi, 030000, China

Location

Sichuan Cancer Hospital. ( Site 0050)

Chengdu, Sichuan, 610041, China

Location

West China Hospital, Sichuan University ( Site 0044)

Chengdu, Sichuan, 610066, China

Location

The Affiliated Cancer Hospital of Xinjiang Medical University ( Site 0049)

Ürümqi, Xinjiang, 830000, China

Location

Yunnan Province Cancer Hospital-Colorectal surgery ( Site 0006)

Kunming, Yunnan, 650106, China

Location

Zhejiang Cancer Hospital-oncology-abdominal neoplasms ( Site 0028)

Hangzhou, Zhejiang, 310022, China

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Colorectal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Oxaliplatin; Leucovorin; Fluorouracil; Irinotecan; Bevacizumab; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2022
• First Posted: February 15, 2022
• Study Start: April 2, 2022
• Primary Completion (Estimated): September 19, 2028
• Study Completion (Estimated): September 19, 2028
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

CN (32)