Clinical trial NCT05600309: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
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)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-10-31
Enrollment: 94
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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 26 months
Secondary outcomes:
measure: 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)
timeFrame: Up to approximately 19 months
measure: Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR
timeFrame: Up to approximately 19 months
measure: Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
timeFrame: Up to approximately 19 months
measure: Number of Participants Who Experience at least One Adverse Event (AE)
timeFrame: Up to approximately 27 months
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Affiliated Hospital of Anhui Medical University ( Site 1179)
state: Anhui
city: Chongqing
country: China
facility: Chongqing Cancer Hospital ( Site 1151)
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Province Cancer Hospital ( Site 1178)
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center ( Site 1150)
state: Guangdong
city: Guangzhou
country: China
facility: Southern Medical University Nanfang Hospital ( Site 1154)
state: Guangdong
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-sen University ( Site 1159)
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital ( Site 1158)
state: Guangxi
city: Haikou
country: China
facility: Hainan General Hospital ( Site 1177)
state: Hainan
city: Wuhan
country: China
facility: Wuhan Union Hospital Cancer Center ( Site 1162)
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital ( Site 1152)
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University ( Site 1171)
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital ( Site 1174)
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University ( Site 1175)
state: Hunan
city: Changzhou
country: China
facility: Changzhou Cancer Hospital-Department of Oncology ( Site 1183)
state: Jiangsu
city: Wuxi City
country: China
facility: Affiliated Hospital of Jiangnan University(Wuxi Fourth People's Hospital ) ( Site 1185)
state: Jiangsu
city: Changchun
country: China
facility: Jilin Cancer Hospital ( Site 1163)
state: Jilin
city: Jinan
country: China
facility: Jinan Central Hospital ( Site 1167)
state: Shandong
city: Shangai
country: China
facility: Fudan University Shanghai Cancer Center ( Site 1176)
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital ( Site 1170)
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital Sichuan University ( Site 1172)
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital ( Site 1161)
state: Tianjin
city: Kunming
country: China
facility: Yunnan Province Cancer Hospital-Colorectal surgery ( Site 1169)
state: Yunnan
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital ( Site 1180)
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital-Medical Oncology ( Site 1173)
state: Zhejiang
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: