A Study of Belzutifan (MK-6482) Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in Participants With Clear Cell Renal Cell Carcinoma Post Nephrectomy (MK-6482-022)

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of RCC with clear cellcomponent per American Joint Committee on Cancer (AJCC) (8th Edition), with orwithout sarcomatoid features

• Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC asdefined by the following pathological tumor-node metastasis and tumor grading:

1. Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, anygrade, N0, M0

2. High risk RCC: pT4, any Grade N0, M0; pT any stage, any Grade, N+, M0

3. M1 NED RCC participants who present not only with the primary kidney tumor butalso solid, isolated, soft tissue metastases that can be completely resected atone of the following: the time of nephrectomy (synchronous) or, ≤2 years fromnephrectomy (metachronous)

• Has undergone complete resection of the primary tumor (partial or radicalnephrectomy) and complete resection of solid, isolated, soft tissue metastaticlesion(s) in M1 NED participants

• Must have undergone a nephrectomy and/or metastasectomy ≤12 weeks prior torandomization

• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10days before randomization.

• Male participants must agree to continue contraception at least 7 days after thelast dose of belzutifan/placebo

• Female participants of childbearing potential must be willing to use an adequatemethod of contraception, for the course of the study through 120 days after the lastdose of pembrolizumab or at least 30 days after last dose of belzutifan/placebo,whichever occurs last

• Has adequate organ function

Exclusion Criteria:

• Has had a major surgery, other than nephrectomy plus resection of preexistingmetastases for M1 NED participants, within 4 weeks prior to randomization

• Has a pulse oximeter reading <92% at rest, requires intermittent supplementaloxygen, or requires chronic supplemental oxygen

• Has clinically significant cardiovascular disease within 6 months from first dose ofstudy intervention

• Has other clinically significant disorders such as: serious active nonhealingwound/ulcer/bone fracture; requirement for hemodialysis or peritoneal dialysis

• Has preexisting brain or bone metastatic lesions

• Has received prior systemic therapy for RCC

• Has received prior radiotherapy for RCC

• Has received a live or live-attenuated vaccine within 30 days before the first doseof study intervention; administration of killed vaccines are allowed

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

• Has a known additional malignancy (other than RCC treated with nephrectomy and/ormetastasectomy) that is progressing or has required active treatment within the past 3 years

• Has an active autoimmune disease that has required systemic treatment in past 2years (i.e., with use of disease modifying agents, corticosteroids, orimmunosuppressive drugs); replacement therapy is allowed

• 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

• Has a known history of human immunodeficiency virus (HIV) infection, a known historyof Hepatitis B or known active Hepatitis C virus infection

• Has had an allogenic tissue/solid organ transplant