Clinical trial NCT05239741: Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Chinese Participants With Stage IV Colorectal Cancer (MK-3475-C66)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
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)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-02-15
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Inclusion Criteria:

Inclusion Criteria include, but are not limited to:

* 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

Exclusion Criteria:

Exclusion Criteria include, but are not limited to:

* 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
* 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 HIV-infection with a history of Kaposi's sarcoma or Multicentric Castleman's Disease
* Has had an allogenic tissue/solid organ transplant

Primary outcomes:
measure: 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
timeFrame: Up to approximately 77 months
measure: 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
timeFrame: Up to approximately 77 months
Secondary outcomes:
measure: Overall Survival (OS) For All Participants
timeFrame: Up to approximately 77 months
measure: Overall Survival (OS) For RAS Wild-type Participants
timeFrame: Up to approximately 77 months
measure: 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
timeFrame: Up to approximately 77 months
measure: 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
timeFrame: Up to approximately 77 months
measure: Number of Participants Who Experience at Least One Adverse Event (AE)
timeFrame: Up to approximately 77 months
measure: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
timeFrame: Up to approximately 77 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer hospital-Digestive Oncology ( Site 0001)
state: Beijing
city: Beijing
country: China
facility: Beijing Peking Union Medical College Hospital-Medical Oncology ( Site 0011)
state: Beijing
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital-Gastric oncology ( Site 0019)
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University ( Site 0051)
state: Chongqing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital-Medical Oncology ( Site 0012)
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital ( Site 0009)
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center ( Site 0047)
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital ( Site 0035)
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University ( Site 0014)
state: Guangdong
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-sen University-Oncology ( Site 0048)
state: Guangdong
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College ( Site 0036)
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital ( Site 0039)
state: Guangxi
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital ( Site 0007)
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital-henan cancer hospital ( Site 0015)
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical,Science & Technology-oncology ( Site 0018)
state: Hubei
city: Wuhan
country: China
facility: Wuhan Union Hospital Cancer Center-Cancer Center ( Site 0008)
state: Hubei
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University ( Site 0031)
state: Hunan
city: Jiangyin
country: China
facility: The Affiliated Jiangyin Hospital of Southeast University Medical College ( Site 0037)
state: Jiangsu
city: NanJing
country: China
facility: Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Oncology ( Site 0002)
state: Jiangsu
city: Shemyang
country: China
facility: The first affiliated hospital of China medical university ( Site 0043)
state: Liaoning
city: Xi'an
country: China
facility: Tangdu Hospital of Fourth Military Medical University of Chi-General Surgery ( Site 0045)
state: Shaanxi
city: Jinan
country: China
facility: Jinan Central Hospital-oncology department ( Site 0021)
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital ( Site 0041)
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center-Oncology ( Site 0046)
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital ( Site 0022)
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Changhai Hospital ( Site 0024)
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Cancer Hospital ( Site 0032)
state: Shanxi
city: Cheng Du
country: China
facility: West China Hospital of Sichuan University ( Site 0044)
state: Sichuan
city: Chengdu
country: China
facility: Sichuan Cancer Hospital. ( Site 0050)
state: Sichuan
city: Urumqi
country: China
facility: The Affiliated Cancer Hospital of Xinjiang Medical University ( Site 0049)
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Province Cancer Hospital-Colorectal surgery ( Site 0006)
state: Yunnan
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital-oncology-abdominal neoplasms ( Site 0028)
state: Zhejiang
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: