A Multicenter, Randomized, Double-Blind, Phase 2, Basket Study of MK-4280A, a Coformulation of Favezelimab (MK-4280) with Pembrolizumab (MK-3475) in Selected Solid Tumors.

Inclusion Criteria

Cohort A only

- Histologically confirmed diagnosis of resectable cutaneous squamous cell carcinoma

(cSCC) as the primary site of malignancy (metastatic skin involvement from another

primary cancer or from an unknown primary cancer is not permitted)

- Stage II to Stage IV disease without distant metastasis (M1). cSCC tumors arising in

the head and neck will be staged according to American Joint Committee on Cancer

(AJCC) Edition (Ed.) 8 and cSCC tumors arising in non-head and neck locations will

be staged according to Union for International Cancer Control (UICC) Ed. 8

- Is systemic treatment naïve

- Archival tumor tissue sample, or newly obtained surgical resection, or biopsy sample

of a tumor lesion not previously irradiated has been provided

- Is an individual of any sex/gender, at least 18 years of age at the time of

providing the informed consent

Cohort B only

- Histologically confirmed diagnosis of endometrial cancer (EC) that is not deficient

in mismatch repair (dMMR) proficient in mismatch repair (pMMR) as documented by a

local test report

- Documented evidence of stage IVB (per 2009 International Federation of Gynecology

and Obstetrics (FIGO) staging), recurrent, or metastatic EC, and are not candidates

for curative surgery or radiation

- Has radiographic evidence of disease progression after 1 prior systemic,

platinum-based chemotherapy regimen for EC in any setting

- Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) by

investigator (before first dose of study intervention)

- Is assigned female sex at birth, at least 18 years of age at the time of providing

the informed consent

- Has adequately controlled blood pressure without antihypertensive medication

All Cohorts

- Agrees to follow contraception guidelines if a participant of childbearing potential

- Has a life expectancy >3 years per investigator assessment

- Has adequate organ function

- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- If positive for hepatitis B, has received antiviral therapy for ≥4 weeks and

undetectable viral load prior to randomization

- If positive for hepatitis C, has undetectable viral load at screening

- If positive for human immunodeficiency virus (HIV), has well-controlled HIV on a

stable highly active antiretroviral therapy

Exclusion Criteria

All Cohorts

- Has known hypersensitivity to active substances or their excipients including

previous clinically significant hypersensitivity reaction to treatment with other

monoclonal antibody (mAb)

- History of allogeneic tissue/solid organ transplant

Cohort A only

- Received prior radiotherapy to the index lesion (in-field lesion)

- Participants for whom the primary site of cSCC was anogenital area (penis, scrotum,

vulva, perianal region) are not eligible

Cohort B

- Has had major surgery within 3 weeks prior to first dose of study interventions

- Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula

- Has urine protein ≥1 g/24 hours

- Has a left ventricle ejection fraction (LVEF) below the institutional (or local

laboratory) normal range, as determined by multi-gated acquisition (MUGA) or

echocardiogram (ECHO)

- Has radiographic evidence of encasement or invasion of a major blood vessel, or of

intratumoral cavitation

- Has clinically significant cardiovascular disease within 12 months from first dose

of study intervention