Phase II Trial of Single Agent Belzutifan or Pembrolizumab Versus Combination as Neoadjuvant Therapy in Clear Cell Renal Cell Carcinoma (BLAZE)

To learn if belzutifan alone, pembrolizumab alone, or belzutifan and pembrolizumab in combination given before a total or partial nephrectomy (surgery to remove all or part of a kidney) can help to control locally advanced ccRCC.

Primary Objective: 1\. A composite primary endpoint of objective response rate (ORR) or pathologic response rate (PRR) at 12 weeks after neoadjuvant therapy. objective response - defined as partial \[≥ 30% decrease in largest diameter\] or complete response on imaging at 12 weeks after neoadjuvant therapy (according to Response Evaluation Criteria In Solid Tumors \[RECIST\] criteria) (Appendix 14.2) Pathologic response - defined as ≤25% residual viable tumor in post-therapy pathology specimen. Secondary Objectives: 1. Relapse-Free Survival (RFS) - defined as the length of time after randomization to date of radiographic/clinical progression, recurrence or death 2. Safety/Tolerability - including adverse events \[by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE)\], laboratory results, vital signs, physical examinations 3. Quality of Life - as measured by patient-reported outcome measures, including EORTC-QLQ-C30 and FACT-G Single Item GP5 (Appendix 14.3, Appendix 14.4)