Study to Evaluate Safety, Pharmacokinetics and Therapeutic Activity of RO6874281 as a Combination Therapy in Participants With Unresectable Advanced and/or Metastatic Renal Cell Carcinoma (RCC)

An Open-Label, Multi-Center, Randomized, Dose-Escalation, Phase 1b Study to Evaluate Safety, Pharmacokinetics and Therapeutic Activity of RO6874281 in Combination With Atezolizumab ± Bevacizumab in Patients With Unresectable Advanced and/or Metastatic Renal Cell Carcinoma

This is an open-label, multi-center, randomized, Phase 1b, adaptive, clinical study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary therapeutic activity of RO6874281 in combination with atezolizumab with/without bevacizumab in participants with unresectable advanced and/or metastatic RCC. The study will consist of a dose-escalation part and an extension part.

Inclusion criteria:

• Unresectable advanced and/or metastatic RCC with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic therapy, including treatment in the adjuvant setting
• During dose escalation only, an additional population with unresectable advanced and/or metastatic 2nd line RCC patients is allowed
• At least one tumor lesion with location accessible to biopsy per clinical judgment of the treating physician
• Consent to provide an archival tumor tissue sample (if available) and to undergo baseline and on treatment tumor biopsies for pharmacodynamic biomarker analysis
• Measurable disease, as defined by RECIST v1.1. At least one lesion accessible for biopsy
• Participants with unilateral pleural effusion are eligible if they fulfill both of the following: (a) New York Heart Association (NYHA) Class 1; (b) Global initiative for obstructive lung disease (GOLD) test level 1 (forced expiratory volume in 1 second [FEV1]/ forced vital capacity [FVC] less than [<] 0.7 and FEV1 greater than or equal to [>=] 80 percent [%] predicted after inhaled bronchodilator)

Adequate hematological function: neutrophil count of ≥1.5 ≥109 cells/L, platelet count of ≥100,000/≥L, Hb ≥9 g/dL (5.6 mmol/L), lymphocytes ≥0.8 ≥109 cells/L.

Exclusion Criteria:

• Symptomatic or untreated central nervous system (CNS) metastases
• Participants with asymptomatic CNS metastases with previous or concomitant brain deficiencies, as defined in the protocol
• Participants with confirmed bilateral pleural effusion
• Episode of significant cardiovascular/cerebrovascular acute disease within 6 months prior to Cycle 1 Day 1
• Active or uncontrolled infections
• Human immunodeficiency virus (HIV) or active Hepatitis A, B, C, D and E virus (HAV, HBV, HCV, HDV and HEV) infection.
• Major surgery or significant traumatic injury <28 days prior to Cycle 1 Day 1 (excluding fine needle biopsies) or anticipation of the need for major surgery during study treatment
• Serious, non-healing wound; active ulcer; or untreated bone fracture
• Proteinuria as demonstrated by a urine protein to creatinine ratio (UPCR) of >=1.0 at screening
• History of, active or suspicion of autoimmune disease
• Concurrent use of high dose of systemic steroids. The use of inhaled, topical and ophthalmic steroids is allowed.