A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC)
Condition: Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Bevacizumab; Sunitinib
Intervention description: Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Days 1 and 22 of each 42-day cycle.; Bevacizumab will be administered at a dose of 15 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 22 of each 42-day cycle.; Sunitinib will be administered at a dose of 50 mg once daily, orally via capsule, on Day 1 through Day 28 of each 42-day cycle.
Intervention MeSH terms: Bevacizumab; Atezolizumab; Sunitinib; Antibodies; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 915.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This multi-center, randomized, open-label study will evaluate the efficacy and safety of
      atezolizumab plus bevacizumab versus sunitinib in participants with inoperable, locally
      advanced, or metastatic RCC who have not received prior systemic active or experimental
      therapy, either in the adjuvant or metastatic setting.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Definitive diagnosis of unresectable locally advanced or metastatic RCC with
             clear-cell histology and/or a component of sarcomatoid carcinoma, with no prior
             treatment in the metastatic setting

          -  Evaluable Memorial Sloan Kettering Cancer Center risk score

          -  Measurable disease, as defined by RECIST v1.1

          -  Karnofsky performance status greater than or equal to 70%

          -  Adequate hematologic and end-organ function prior to randomization

        Exclusion Criteria:

        Disease-Specific Exclusions:

          -  Radiotherapy for RCC within 14 days prior to treatment

          -  Active central nervous system disease

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites

          -  Uncontrolled hypercalcemia

          -  Any other malignancies within 5 years except for low-risk prostate cancer or those
             with negligible risk of metastasis or death

        General Medical Exclusions:

          -  Life expectancy less than 12 weeks

          -  Participation in another experimental drug study within 4 weeks prior to treatment

          -  Pregnant or lactating women

          -  Known hypersensitivity to any component of atezolizumab or other study medication

          -  History of autoimmune disease except controlled, treated hypothyroidism or type I
             diabetes mellitus

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis, or idiopathic pneumonitis

          -  Positive human immunodeficiency virus test

          -  Active or chronic hepatitis B or C

          -  Severe infections within 4 weeks prior to treatment

          -  Exposure to oral or IV antibiotics within 2 weeks prior to treatment

          -  Live attenuated vaccines within 4 weeks prior to treatment (for influenza vaccination
             participants must agree not to receive live, attenuated influenza vaccine within 4
             weeks prior to treatment, during treatment or within 5 months following the last dose)

          -  Significant cardiovascular disease

          -  Prior allogeneic stem cell or solid organ transplantation

        Exclusion Criteria Related to Medications:

          -  Prior treatment with cluster of differentiation 137 agonists, anti-cytotoxic
             T-lymphocyte associated protein-4, anti-programmed death (PD)-1, or anti-PD-L1
             therapeutic antibody or pathway-targeting agents

          -  Treatment with immunostimulatory agents for non-malignant conditions within 6 weeks or
             immunosuppressive agents within 2 weeks prior to treatment

        Bevacizumab- and Sunitinib-Specific Exclusions:

          -  History of hypertensive crisis or hypertensive encephalopathy

          -  Baseline electrocardiogram showing corrected QT interval greater than 460 milliseconds