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)

Inclusion Criteria:

• Has a histologically confirmed colorectal adenocarcinoma that is metastatic andunresectable.

• 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 orafter or could not tolerate standard treatment.

• Submits an archival (≤ 5 years) or newly obtained tumor tissue sample or newlyobtained tumor tissue sample that has not been previously irradiated.

• Has an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 to 1within 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 clinicallysignificant gastrointestinal abnormalities that might alter absorption.

• Has adequate organ function.

Exclusion Criteria:

• Has previously been found to have deficient mismatch repair/microsatelliteinstability-high (dMMR/MSI-H) tumor status.

• Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis 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, spinalmuscular atrophy).

• Has clinically significant cardiovascular disease within 12 months from first doseof study intervention, including New York Heart Association Class III or IVcongestive heart failure, unstable angina, myocardial infarction, cerebral vascularaccident, 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 testwithin 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 kinaseinhibitor (TKI; eg, lenvatinib) other than rapidly accelerated fibrosarcoma (RAF)inhibitors (binimetinib is permitted if combined with a RAF inhibitor), or with anagent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxicT-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 agentswithin 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 requirecorticosteroids, and not have had radiation pneumonitis. A 1-week washout ispermitted 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 doseof study intervention.

• Has a known additional malignancy that is progressing or has required activetreatment within the past 3 years.

• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of itsexcipients.

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

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

• Has an active infection requiring systemic therapy (eg, tuberculosis, known viral orbacterial 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 laboratoryabnormality that might confound the results of the study, interfere with theparticipant's participation for the full duration of the study, or is not in thebest interest of the participant to participate, in the opinion of the treatinginvestigator.

• Has had an allogenic tissue/solid organ transplant.