Study of Atezolizumab + Bevacizumab in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma

Inclusion Criteria

• Age ≥ 18 years.
• Unresectable advanced or metastatic non-clear cell RCC to include but not limited to:
• Papillary RCC, any type
• Unclassified RCC
• Translocation RCC
• Chromophobe RCC
• Collecting duct RCC
• Medulary RCC
• Clear cell RCC or any histology with > 20% sarcomatoid features will be eligible.
• Other non-clear cell histologies that are not included above need to be discussed with the PI.
• Request for formalin-fixed, paraffin-embedded (FFPE) archival tumor specimens if available and willingness of the participant to undergo mandatory fresh tumor biopsy unless determined medically unsafe or not feasible. A note from the study team should be provided documenting availability of tissue. If a target lesion is biopsied at screening, this lesion must be followed as non-target lesion after the biopsy unless it is the patient's only target lesion. If there is only one target lesion, it should be followed as a target lesion regardless.
• The archival specimen should contain adequate viable tumor tissue.
• The specimen may consist of a tissue block (preferred and should contain the highest grade of tumor) or at least 30 unstained serial sections. Fine-needle aspiration, brushings, cell pellet from pleural effusion, bone marrow aspirate/biopsy are not acceptable.
• Fresh tumor biopsy at progression will be required in cases where patients experience relapse after an initial response if medically safe.
• Measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
• ECOG performance status ≤ 2 (See Appendix A).
• Adequate hematologic and end-organ function as defined by the following laboratory results obtained within 28 days prior to the first study treatment:
• Absolute neutrophil count (ANC) ≥ 1500 cells/uL.
• Lymphocyte count ≥ 500/uL.
• Platelet count ≥ 100,000/uL.
• Hemoglobin ≥ 9 g/dL (patients may be transfused to meet this criterion).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) with the following exceptions: Patients with documented liver metastases should have AST and ALT ≤ 5 x ULN.
• Serum bilirubin ≤ 2.0 x ULN with the following exception: Patients with known Gilbert's disease should have a serum bilirubin ≤ 3 x ULN.
• Creatinine clearance ≥ 30 mL/min as calculated by Cockcroft-Gault equation.
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective forms of contraception and to continue its use 6 months after the last dose of atezolizumab or bevacizumab.
• Signed informed consent form.
• Ability and capacity to comply with study and follow-up procedures.

Exclusion Criteria

•Prior treatment with CD137 agonists, anti- cytotoxic T-lymphocyte-associated protein 4, anti-PD-1, or anti-PDL1 therapeutic antibody or pathway targeting agents.

Prior IFNα or IL-2 is allowed following 4 week washout from treatment end date.

• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitors) within 2 weeks of enrollment or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 4 weeks of enrollment.
• Prior therapy with bevacizuamab.
• Thrombologic event within 3 weeks of treatment start date, unless stable on anticoagulation with LMWH or Factor Xa inhibitor for at least 2 weeks.
• Treatment with systemic immunosuppressive medications including but not limited to: prednisone, dexamethasone, cyclosporin, azathioprine, methotrexate, thalidomide, anti- tumor necrosis factor (TNF) agents, hydroxychloroquine within 2 weeks of first study dose.
• Patients who have received acute, low-dose systemic immunosuppressant medications may be enrolled.
• Patients with adrenal insufficiency on physiologic replacement doses of steroids may be enrolled.
• The use of inhaled, topical intraocular, or intra ar