Brigham Research Institute (BRI) - Brigham and Women's Hospital

• 18 years of age or older at screening - Locally advanced (not amenable to curative surgery or radiation therapy) or metastatic RCC with diagnosis confirmed by histology/cytology - At least one measurable (as defined by the investigator) and untreated lesion - Adequate hematologic, hepatic, cardiac and renal function - No prior systemic therapy for RCC (immunotherapy after surgery is allowed if received >12 months prior) - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. - All International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) based risk categories

Participants may be excluded if they meet any of the following: - Known active brain lesions including leptomeningeal metastasis, brainstem, meningeal or spinal cord metastases or compression. - Clinically significant risk of haemorrhage or fistula - History of another malignancy within 3 years - History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. - active autoimmune diseases requiring systemic treatment within the past 2 years - uncontrolled cardiac and other comorbidities within 6 months prior to the first dose - Major surgery or severe trauma within 4 weeks before the first dose, or planned major surgery during the study - History of severe bleeding tendency or coagulation dysfunction - History of oesophageal varices, severe ulcers, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess or acute gastrointestinal bleeding within 6 months prior to the first dose - Acute, chronic or symptomatic infections - Participants with history of immunodeficiency