Atezolizumab With Bevacizumab in Previously Untreated Metastatic/Unresectable Urothelial Cancer

INCLUSION CRITERIA Patient must meet all of the following applicable inclusion criteria to participate in this study: * Written informed consent and Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization for release of personal health information. * As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study * Age ≥ 18 years at the time of consent * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 within 28 days prior to registration * Histological or cytological evidence urothelial (transitional cell) carcinoma of the renal pelvis, ureter, bladder or urethra * Locally advanced/unresectable disease as determined by site attending urologic oncologist or metastatic disease * Evaluable untreated tumor tissue for biomarker analysis. Untreated tumor tissue is defined as no intervening intravesical or systemic therapy since acquisition. Patients without tissue available must be willing and safe to undergo biopsy repeat biopsy (core needle or excisional) prior to enrollment. Subjects with \< 25 slides may be enrolled after discussion with the sponsor-investigator or co-investigator. * Willing to undergo a core needle or excisional biopsy on-treatment. Patients will be assessed at the time of biopsy for safety of undergoing the procedure * Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 within 28 days prior to registration * No prior chemotherapy for locally advanced or metastatic urothelial cancer * Perioperative chemotherapy previously administered in the neoadjuvant and/or adjuvant setting is permitted * Prior chemotherapy administered in the context of chemoradiation as definitive treatment for bladder preservation is also permitted, provided that disease progression outside the prior radiotherapy field is demonstrated histologically or cytologically * Ineligible for cisplatin as defined by presence of one or more of the following: * (Impaired renal function \[≤ 60 cc/min\]. Glomerular filtration rate (GFR) should be assessed by direct measurement \[i.e., creatinine clearance or ethylenediaminetetra-acetate\] or, if not available, by calculation from serum/plasma creatinine by Cockroft-Gault equation) * Grade ≥ 2 hearing Loss (measured by loss of \>25 dB at two contiguous frequencies in at least one ear for patients undergoing serial audiometry testing) * Grade ≥ 2 peripheral neuropathy * ECOG Performance Status of 2 * Solitary Kidney * Refusing Cisplatin-based chemotherapy * If palliative radiotherapy administered, completion of palliative radiation therapy ≥ 2 weeks prior to Cycle 1 Day 1 of protocol therapy * Females of childbearing potential must have a negative serum pregnancy test within 28 days prior to registration. * Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use 2 forms of effective methods of contraception from the time of informed consent until 150 days (5 months) after discontinuation of atezolizumab or 180 days (6 months) after discontinuation of bevacizumab. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method EXCLUSION CRITERIA Patients meeting any of the criteria below may not participate in the study: * Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment; the following exceptions are allowed: * Palliative radiotherapy for bone metastases or soft tissue lesions should be completed \> 7 days prior to baseline imaging * Hormone-replacement therapy or oral contraceptives * Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment * Active or untreated central nervous system (CNS) metastases or leptomeningeal disease as determined by computed tomography (CT) scan or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments. * Patients with treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria: * Evaluable or measurable disease outside the CNS * No metastases to midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm) * No history of intracranial or spinal cord hemorrhage * No evidence of significant vasogenic edema * No ongoing requirement for dexamethasone as therapy for CNS disease; anticonvulsants at a stable dose allowed * No stereotactic radiation, whole-brain radiation within 4 weeks prior to Cycle 1 Day 1 * Patients with central nervous system (CNS) metastases treated by neurosurgical resection or brain biopsy within 3 months prior to Cycle 1 Day 1 will be excluded * Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study * Screening CNS radiographic study ≥ 4 weeks since completion of radiotherapy or surgical resection and ≥ 2 weeks since discontinuation of corticosteroids * Leptomeningeal disease * Uncontrolled tumor-related pain * Patients requiring pain medication must be on a stable regimen at study entry * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) * Patients with indwelling drainage catheters are allowed. * Uncontrolled hypercalcemia (\> 1.5 mmol/L ionized calcium or Ca \> 12 mg/dL or corrected serum calcium \> ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. NOTE: Patients with asymptomatic hypercalcemia controlled with medical therapy are eligible. * Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. * Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while in the study. * Malignancies other than urothelial cancer within 5 years prior to Cycle 1 Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (T1/T2a, Gleason score ≤ 3 + 4, and PSA ≤ 0.5 ng/mL undergoing active surveillance and treatment naive) * Pregnant or breastfeeding * History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins * Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab or bevacizumab formulation * History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis * Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. * Subjects with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study. * Subjects with a history of celiac disease may be eligible if controlled with diet. * History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan * History of radiation pneumonitis in the radiation field (fibrosis) is permitted. * History of confirmed positive test for human immunodeficiency virus (HIV) * Patients with active hepatitis B virus (HBV) (chronic or acute, defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C virus (HCV) * Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBc Ab\] and absence of HBsAg) are eligible * Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA * Active tuberculosis * Severe infections within 4 weeks prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia * Signs or symptoms of active infection within 2 weeks prior to C1D1 * Received therapeutic oral or IV antibiotics within 1 week prior to C1D1 * Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible * New York Heart Association Congestive Heart Failure Class II or greater * Myocardial infarction, unstable angina or unstable arrhythmias within 3 months of enrollment. * History of stroke or TIA within 3 months of enrollment * Other clinically significant arterial vascular disease within 6 months of enrollment (e.g. aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis). Prior history of adequately treated venous thromboembolism \> 7 days prior to C1D1 on stable dose of therapeutic anticoagulation is permitted * Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction \< 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate. * Major surgical procedure other than for diagnosis within 28 days prior to C1D1 or anticipation of need for a major surgical procedure during the course of the study * Prior allogeneic stem cell or solid organ transplant * Administration of a live, attenuated vaccine within 4 weeks before C1D1 or anticipation that such a live attenuated vaccine will be required during the study * Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications ATEZOLIZUMAB-SPECIFIC EXCLUSION CRITERIA: * Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies * Prior cancer vaccines and cellular immunotherapy are permitted. * Treatment with systemic immunostimulatory agents (including but not limited to IFNs, interleukin \[IL\]-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to C1D1 * Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to C1D1, or anticipated requirement for systemic immunosuppressive medications during the trial * Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled * The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone for adrenal insufficiency) is allowed BEVACIZUMAB-SPECIFIC EXCLUSION CRITERIA: * Inadequately controlled hypertension (defined as persistent systolic blood pressure (SBP) \> 150 and/or diastolic blood pressure (DBP) \> 100 mmHg) * Prior history of hypertensive crisis or hypertensive encephalopathy * Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) * Current or recent (within 10 days of study enrollment) use of aspirin (\> 325 mg/day), clopidogrel (\> 75 mg/day), or current or recent (within 10 days prior to first dose of bevacizumab) use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes * History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month of study enrollment * Minor surgical procedure within 7 calendar days prior to C1D1 * History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to enrollment * Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding * Evidence of abdominal free air not explained by paracentesis or recent surgical procedure * Serious non-healing or dehiscing wound, active ulcer, or untreated or non-healing bone fracture * On-going gross hematuria associated with clots