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

Colorectal Neoplasms Clinical Trial

Official title:

A Phase 3 Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Chinese Participants With Stage IV Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Colorectal Cancer (MK-3475-C66)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05239741
• Other study ID #: 3475-C66
• Secondary ID: MK-3475-C66
• Status: Recruiting
• Phase: Phase 3
• Start date: April 2, 2022
• Est. completion date: November 10, 2026

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 10, 2026
• Est. primary completion date: November 10, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• 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 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 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

Exclusion Criteria:

• 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-PD-1, anti-PD-L1, or 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

• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.

• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication

• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years, with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis

• Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients

• Has an active autoimmune disease that has required systemic treatment in past 2 years

• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease

• Has an active infection requiring systemic therapy (eg, tuberculosis, known viral or bacterial infection)

• Has a known history of human immunodeficiency virus (HIV) infection

• Has a known history of Hepatitis B or known Hepatitis C virus infection

• Has had an allogenic tissue/solid organ transplant

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Biological:
• Pembrolizumab
Intravenous (IV) infusion

Drug:
• Oxaliplatin
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
• Leucovorin
400 mg/m^2 given as an IV on Day 1 Q2W as part of the mFOLFOX6 and FOLFIRI regimens
• 5-fluorouracil
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
• Irinotecan
180 mg/m^2 IV on Day 1 Q2W as part of the FOLFIRI regimen

Biological:
• Bevacizumab
IV infusion
• Cetuximab
IV infusion

Locations

Country	Name	City	State
China	Beijing Cancer hospital-Digestive Oncology ( Site 0001)	Beijing	Beijing
China	Beijing Peking Union Medical College Hospital-Medical Oncology ( Site 0011)	Beijing	Beijing
China	The Third Xiangya Hospital of Central South University ( Site 0031)	Changsha	Hunan
China	West China Hospital of Sichuan University ( Site 0044)	Cheng Du	Sichuan
China	Chongqing University Cancer Hospital-Medical Oncology ( Site 0012)	Chongqing	Chongqing
China	Fujian Provincial Cancer Hospital-oncology department ( Site 0009)	Fuzhou	Fujian
China	Guangdong Provincial People's Hospital ( Site 0035)	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University ( Site 0014)	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital-oncology-abdominal neoplasms ( Site 0028)	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital-Harbin Medical University Cancer Hospital ( Site 0007)	Harbin	Heilongjiang
China	The Affiliated Jiangyin Hospital of Southeast University Medical College ( Site 0037)	Jiangyin	Jiangsu
China	Jinan Central Hospital-oncology department ( Site 0021)	Jinan	Shandong
China	Shandong Cancer Hospital ( Site 0041)	Jinan	Shandong
China	Yunnan Province Cancer Hospital-Colorectal surgery ( Site 0006)	Kunming	Yunnan
China	Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Oncology (	NanJing	Jiangsu
China	Guangxi Medical University Affiliated Tumor Hospital ( Site 0039)	Nanning	Guangxi
China	Fudan University Shanghai Cancer Center-Oncology ( Site 0046)	Shanghai	Shanghai
China	Shanghai Changhai Hospital ( Site 0024)	Shanghai	Shanghai
China	Shanghai East Hospital ( Site 0022)	Shanghai	Shanghai
China	Cancer Hospital of Shantou University Medical College ( Site 0036)	Shantou	Guangdong
China	The first affiliated hospital of China medical university ( Site 0043)	Shenyang	Liaoning
China	Shanxi Cancer Hospital ( Site 0032)	Taiyuan	Shanxi
China	Tianjin Medical University Cancer Institute and Hospital-Gastric oncology ( Site 0019)	Tianjin	Tianjin
China	Tongji Hospital Tongji Medical,Science & Technology-oncology ( Site 0018)	Wuhan	Hubei
China	Wuhan Union Hospital Cancer Center-Cancer Center ( Site 0008)	Wuhan	Hubei
China	Tangdu Hospital of Fourth Military Medical University of Chi-General Surgery ( Site 0045)	Xi'an	Shaanxi
China	Henan Cancer Hospital-henan cancer hospital ( Site 0015)	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 54 months
Primary	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 54 months
Secondary	Overall Survival (OS) For All Participants	OS is defined as the time from randomization to death due to any cause. The OS will be reported for all participants.	Up to approximately 54 months
Secondary	Overall Survival (OS) For RAS Wild-type Participants	OS is defined as the time from randomization to death due to any cause. The OS will be reported for RAS wild-type participants.	Up to approximately 54 months
Secondary	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	ORR is defined as the percentage of participants who have a best response of confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage for all participants who experience CR or PR as assessed by BICR will be presented.	Up to approximately 54 months
Secondary	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	ORR is defined as the percentage of participants who have a best response of confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage for RAS wild-type participants who experience CR or PR as assessed by BICR will be presented.	Up to approximately 54 months
Secondary	Number of Participants Who Experience at Least One Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported.	Up to approximately 54 months
Secondary	Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported.	Up to approximately 54 months

External Links

•   Merck Oncology Clinical Trials Information