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

A Phase 3 Study of MK-4280A (Coformulated Favezelimab [MK-4280] Plus Pembrolizumab [MK-3475]) Versus Standard of Care in Previously Treated Metastatic PD-L1 Positive Colorectal Cancer (KEYFORM-007)

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Biological: favezelimab/pembrolizumab; Drug: regorafenib; Drug: TAS-102

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.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Affiliated Hospital of Anhui Medical University ( Site 1179)
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400030
      • Chongqing Cancer Hospital ( Site 1151)
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Province Cancer Hospital ( Site 1178)
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center ( Site 1150)
    • Guangzhou, Guangdong, China, 510515
      • Southern Medical University Nanfang Hospital ( Site 1154)
    • Guangzhou, Guangdong, China, 510655
      • The Sixth Affiliated Hospital of Sun Yat-sen University ( Site 1159)
  • Guangxi
    • Nanning, Guangxi, China, 531021
      • Guangxi Medical University Affiliated Tumor Hospital ( Site 1158)
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital ( Site 1177)
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Union Hospital Cancer Center ( Site 1162)
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital ( Site 1152)
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University ( Site 1171)
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital ( Site 1174)
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University ( Site 1175)
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • Changzhou Cancer Hospital-Department of Oncology ( Site 1183)
    • Wuxi, Jiangsu, China, 214122
      • Affiliated Hospital of Jiangnan University(Wuxi Fourth People's Hospital ) ( Site 1185)
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Cancer Hospital ( Site 1163)
  • Shandong
    • Jinan, Shandong, China, 250000
      • Jinan Central Hospital ( Site 1167)
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200072
      • Shanghai Tenth People's Hospital ( Site 1170)
    • Shanghai, Shanghai Municipality, China, 201321
      • Fudan University Shanghai Cancer Center ( Site 1176)
  • Sichuan
    • Chengdu, Sichuan, China, 332001
      • West China Hospital Sichuan University ( Site 1172)
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital ( Site 1161)
  • Yunnan
    • Kunming, Yunnan, China, 650106
      • Yunnan Province Cancer Hospital-Colorectal surgery ( Site 1169)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Zhejiang Cancer Hospital ( Site 1180)
    • Hangzhou, Zhejiang, China, 310018
      • Sir Run Run Shaw Hospital-Medical Oncology ( Site 1173)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: favezelimab/pembrolizumab; Coformulated favezelimab/pembrolizumab (800 mg/200 mg), IV infusion; Other Names: MK-4280A
Active Comparator: Standard of Care (Regorafenib or 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.	Drug: regorafenib; Oral; Other Names: STIVARGA®; REGONIX®; Drug: TAS-102; Oral; Other Names: LONSURF®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause.	Up to approximately 26 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	PFS was 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 occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.	Up to approximately 26 months
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	ORR was defined as the percentage of participants who achieved a 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 lesion) per RECIST 1.1 as assessed by BICR	Up to approximately 26 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR	For participants who demonstrate confirmed CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions), duration of response was defined as the time from the first documented evidence of CR or PR until progressive disease (PD) or death due to any cause. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation.	Up to approximately 26 months
Number of Participants Who Experienced at Least One Adverse Event (AE)	An AE was 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.	Up to approximately 20 months
Number of Participants Who Discontinued Study Treatment Due to an AE	An AE was 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 is presented.	Up to approximately 17 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2022
• Primary Completion (Actual): August 15, 2024
• Study Completion (Actual): February 21, 2025

Study Registration Dates

• First Submitted: October 26, 2022
• First Submitted That Met QC Criteria: October 26, 2022
• First Posted (Actual): October 31, 2022

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Programmed Cell Death-1 (PD1, PD-1),; Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1); Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; trifluridine tipiracil drug combination; pembrolizumab; regorafenib
• Other Study ID Numbers: 4280A-007 China Extension; MK-4280A-007 China Extension (Other Identifier: MSD); jRCT2031210482 (Registry Identifier: jRCT(Japan Registry of Clinical Trials))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes