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)

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 hepatitis B virus (HBV) or hepatitis C virus
(HCV) 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.