This Phase 3 study enrolls patients with clear cell RCC (with or without sarcomatoid features) with no evidence of disease (NED) after complete resection of primary tumor, if pathology confirms intermediate-high risk (pT2, Grade 4 or sarcomatoid, N0, M0; pT3, any grade, N0, M0), high risk (pT4, any Grade N0, M0; pT any stage, any Grade, N+, M0), or M1 NED (complete resection of a soft tissue metastasis at time of nephrectomy or < 2 years from nephrectomy). Eligible patients must have an Eastern Cooperative Oncology Group performance status of 0 to 1 within 10 days before randomization, must have undergone nephrectomy and/or metastasectomy < 12 weeks prior to randomization, and must have adequate organ function. Patients cannot have had a prior systemic treatment or radiotherapy for RCC, have pulse oximetry of <92% at rest or require supplemental oxygen. Following enrollment, patients are randomized to receive either belzutifan (120 mg orally once daily) for up to 54 weeks plus pembrolizumab (400 mg intravenously every 6 weeks) for up to 9 administrations or placebo plus pembrolizumab for the same duration. Patients will continue to be followed after the time of treatment discontinuation or completion.
The KEYNOTE-564 study, a Phase 3 study evaluating the efficacy of pembrolizumab versus placebo in the adjuvant treatment of clear cell RCC post nephrectomy, extended disease-free survival (DFS) and has thus become an option for adjuvant therapy. Belzutifan, a small molecule hypoxia-inducible factor 2-alpha inhibitor, is a current treatment for patients with RCC associated with von Hippel-Lindau disease. It is possible that the combination of belzutifan and pembrolizumab may provide additive benefit to patients who are candidates for adjuvant therapy after nephrectomy.
The primary endpoint of this trial is disease-free survival (DFS). Key secondary outcomes include overall survival (OS), disease recurrence-specific survival, rate of study treatment discontinuation and rate of participants with one or more adverse events (AEs).