A Study of Coformulated Favezelimab/Pembrolizumab (MK-4280A) Versus Standard of Care in Subjects With Previously Treated Metastatic PD-L1 Positive Colorectal Cancer (MK-4280A-007)-China Extension Study
- Conditions
- Colorectal Cancer
- Interventions
- Registration Number
- NCT05600309
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this China extension study is to assess the safety and efficacy of coformulated favezelimab/pembrolizumab (MK-4280A) in adult Chinese participants with metastatic colorectal cancer. The study will also compare MK-4280A with the standard of care treatment of regorafenib and TAS-102 (trifluridine and tipiracil).
The primary study hypothesis is that coformulated favezelimab/pembrolizumab (MK-4280A) is superior to standard of care with respect to overall survival.
- Detailed Description
The China extension study will include participants previously enrolled in China in the global study for MK-4280A-007 (NCT05064059) plus those enrolled during the China extension enrollment period. A total of approximately 94 Chinese participants will be enrolled.
As of Amendment 3 of the supplemental statistical analysis plan, patient reported outcomes will no longer be secondary outcome measures of the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 94
- Has a histologically confirmed colorectal adenocarcinoma that is metastatic and unresectable.
- Has measurable disease per RECIST 1.1 as assessed by the local site investigator.
- Has been previously treated for the disease and radiographically progressed on or after or could not tolerate standard treatment.
- Submits an archival (≤ 5 years) or newly obtained tumor tissue sample or newly obtained tumor tissue sample that has not been previously irradiated.
- Has an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 to 1 within 10 days prior to first dose of study intervention.
- Has a life expectancy of at least 3 months, based on the investigator assessment.
- Has the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption.
- Has adequate organ function.
- Has previously been found to have deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) tumor status.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease.
- Has a history of acute or chronic pancreatitis.
- Has neuromuscular disorders associated with an elevated creatine kinase (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
- Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
- Has urine protein greater than or equal to 1g/24h.
- A woman of childbearing potential who has a positive urine/serum pregnancy test within 24/72 hours prior to the first dose of study intervention.
- Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2), anti-lymphocyte activation gene 3 (LAG-3) antibody, with a tyrosine kinase inhibitor (TKI; eg, lenvatinib) other than rapidly accelerated fibrosarcoma (RAF) inhibitors (binimetinib is permitted if combined with a RAF inhibitor), or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4, OX-40, cluster of differentiation [CD] 137).
- Has previously received regorafenib or TAS-102.
- Has received prior systemic anticancer therapy including investigational agents within 28 days before randomization.
- Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
- 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 infections, etc.).
- Has a known history of human immunodeficiency virus (HIV) infection.
- Has known history of Hepatitis B or known active Hepatitis C virus infection.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Has had an allogenic tissue/solid organ transplant.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Favezelimab/Pembrolizumab favezelimab/pembrolizumab Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) intravenously (IV) on Day 1, then every 3 weeks (Q3W), for up to 35 infusions. Standard of Care (Regorafenib or TAS-102) regorafenib At the Investigator's choice, participants will receive 160 mg regorafenib orally daily on Days 1-12 of each 28-day cycle or 35 mg/m\^2 TAS-102 orally twice daily on Days 1-5 and Days 8-12 of each 28-day cycle. Standard of Care (Regorafenib or TAS-102) TAS-102 At the Investigator's choice, participants will receive 160 mg regorafenib orally daily on Days 1-12 of each 28-day cycle or 35 mg/m\^2 TAS-102 orally twice daily on Days 1-5 and Days 8-12 of each 28-day cycle.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Up to approximately 26 months OS is defined as the time from randomization to death due to any cause.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) according per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) Up to approximately 19 months PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first.
Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR Up to approximately 19 months For participants who demonstrate confirmed CR or PR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR Up to approximately 19 months The ORR is defined as the percentage of participants who achieve a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by BICR.
Number of Participants Who Discontinue Study Treatment Due to an AE Up to approximately 24 months 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. The number of participants who discontinue study treatment due to an AE will be reported.
Number of Participants Who Experience at least One Adverse Event (AE) Up to approximately 27 months 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.
Trial Locations
- Locations (24)
The Second Affiliated Hospital of Anhui Medical University ( Site 1179)
🇨🇳Hefei, Anhui, China
Chongqing Cancer Hospital ( Site 1151)
🇨🇳Chongqing, Chongqing, China
Fujian Province Cancer Hospital ( Site 1178)
🇨🇳Fuzhou, Fujian, China
Sun Yat-Sen University Cancer Center ( Site 1150)
🇨🇳Guangzhou, Guangdong, China
Southern Medical University Nanfang Hospital ( Site 1154)
🇨🇳Guangzhou, Guangdong, China
The Sixth Affiliated Hospital of Sun Yat-sen University ( Site 1159)
🇨🇳Guangzhou, Guangdong, China
Guangxi Medical University Affiliated Tumor Hospital ( Site 1158)
🇨🇳Nanning, Guangxi, China
Hainan General Hospital ( Site 1177)
🇨🇳Haikou, Hainan, China
Wuhan Union Hospital Cancer Center ( Site 1162)
🇨🇳Wuhan, Hubei, China
Hubei Cancer Hospital ( Site 1152)
🇨🇳Wuhan, Hubei, China
Scroll for more (14 remaining)The Second Affiliated Hospital of Anhui Medical University ( Site 1179)🇨🇳Hefei, Anhui, China