A PHASE IB STUDY OF THE SAFETY AND PHARMACOLOGY OF ATEZOLIZUMAB (ANTI-PD-L1 ANTIBODY) ADMINISTERED WITH IPILIMUMAB, INTERFERON-ALPHA, OR OTHER IMMUNE-MODULATING THERAPIES IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS

Patients must meet the following criteria for study entry:
* Signed Informed Consent Form
* Age * 18 years
* Able to comply with the study protocol, in the investigator*s judgment
* Histologically or cytologically documented locally advanced or metastatic solid tumors meeting the following study drug-specific criteria
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
* Life expectancy * 12 weeks
* Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
* Adequate hematologic and end organ function, defined by the following laboratory test results obtained within 14 days prior to the first study treatment:
ANC * 1500 cells/µL (without granulocyte colony stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
WBC counts > 2500 cells/µL
Lymphocyte count * 250 cells/µL
Serum albumin * 2.5 g/dL
Platelet count * 100,000 cells/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
Hemoglobin * 9.0 g/dL
Patients may be transfused or receive erythropoietic treatment to meet this criterion.
AST, ALT, and alkaline phosphatase * 2.5 × upper limit of normal (ULN), with the following exceptions:
Patients with documented liver or bone metastases: alkaline phosphatase * 5 × ULN
Serum bilirubin * 1.5 × ULN
Patients with known Gilbert disease who have serum bilirubin level * 3 × ULN may be enrolled.
INR and aPTT * 1.5 × ULN
This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
Creatinine clearance * 30 mL/min
Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration, or Modification of Diet in Renal Disease formulae may be used for creatinine clearance calculation. Note that 24-hour urine collection is not required.
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for > 90 days after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 18 months after the last dose of obinutuzumab.
A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (* 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined below:
With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for * 6 months after the last dose of bevacizumab. Men must refrain from donating sperm during this same period.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
* Archival tumor tissue
A representative formalin-fixed paraffin embedded (FFPE) tumor specimen collected at first diagnosis and/or subsequent tumor recurrence(s) consistent with the patient*s diagnosis is required for participation in this study (FFPE block [preferred] or a minimum of 15 unstained serial sections). This specimen must be accompanied by the associated pathology report. The tumor sample and associated pathology report must be confirmed to be available prior to any study-specific screening procedures. Fine-needle aspiration, brushing, cell pellet from pleural effusion, and lavage samples are not acceptable. Tumor tissue from bone metastases is not evaluable for tumor PD-L1 expression and is therefore not acceptable. For core needle biopsy specimens, at least three cores should be submitted for evaluation.
For samples not meeting minimum requirements for size/slide number, contact the Medical Monitor via your site contact with information on tissue size and tumor content/number of slides to determine eligibility.
Alternatively, or if the archival tumor sample does not meet minimum requirements, the patient may be offered the option of undergoing a pre-treatment procedure (excisional or core tumor biopsy) to obtain an adequate tumor sample. Acceptable samples include core needle biopsies for deep tumor tissue (minimum 3 cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. Tumor tissue from bone metastases is not evaluable for tumor PD-L1 expression and is therefore not acceptable.
Patients having additional tissue samples from procedures performed at different times during the course of their cancer will be requested (but not required) to also submit these samples for central testing. Tissue samples obtained at multiple times for individual patients will greatly contribute to an improved understanding of the dynamics of PD-L1 expression and relationship with intervening anti-cancer therapy.;Detailed information about the specific inclusion criteria for Arm A, B, C, D and E can be found on pages 76-78 of the protocol.

Patients who meet any of the following criteria will be excluded from study entry:
Cancer-Specific Exclusions
* NSCLC with sensitizing mutations in EGFR or ALK rearrangements
* Melanoma with BRAF mutations
* Active or untreated CNS metastases as determined by computed tomography (CT) scan or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments; patients with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:
Measureable disease outside the CNS
No metastases to midbrain, pons, or medulla
No history of intracranial or spinal cord hemorrhage
No ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed
No evidence of interim progression * 4 weeks between the completion of CNS-directed therapy and the screening radiographic study
* Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for * 2 weeks prior to screening
* Leptomeningeal disease
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
Patients with indwelling catheters (e.g., PleurX®) are allowed.
* Uncontrolled tumor-related pain
Patients requiring pain medication must be on a stable regimen at study entry.
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to enrollment.
Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not presently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
* Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
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 discontinue its use and receive a bisphosphonate instead while on study.
* History of other malignancy within 2 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, localized prostate cancer treated with curative intent, ductal carcinoma in situ treated surgically with curative intent, or other cancers with a similar outcome;General Medical Exclusions
* Pregnant and lactating women
* Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment, with the following exceptions:
Hormone-replacement therapy or oral contraceptives
Tyrosine kinase inhibitors (TKIs) that have been discontinued > 7 days prior to Cycle 1, Day 1; baseline scans must be obtained after discontinuation of prior TKIs.
* Investigational therapy within 28 days prior to initiation of study treatment
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of the atezolizumab formulation
* History of or active autoimmune disease including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener*s granulomatosis, Sjögren*s syndrome, Bell*s palsy, Guillain Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
Patients with autoimmune thyroid disease or vitiligo may be eligible following consultation with the Medical Monitor.
Patients with controlled Type I diabetes mellitus on a stable insulin regimen may be eligible for this study.
* History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest CT scan
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
* Prior allogeneic bone marrow transplantation or prior solid organ transplantation
* History of HIV (tested prior to inclusion into the study if not in contradiction with local legislation)
* Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening)
Patients with past/resolved hepatitis B virus (HBV) infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1.
Note: For patients in Arm E, patients with past/resolved HBV infection are eligible provided they are willing to undergo regular monthly DNA testing and be placed on prophylactic anti-viral therapy for the duration of obinutuzumab treatment and for 12 months after the last dose of obinutuzumab. Patients who have protective titers of HBsAg after vaccination or prior but cured hepatitis B are eligible.
* Patients with active hepatitis C
Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) 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 infection within 2 weeks prior to Cycle 1, Day 1
* Received therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1
Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
*Patients with a history of confirmed progressive multifocal leukoencephalopathy
* Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months prior to study treatment, unstable arrhythmias, or unstable angina
* Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the study other than for diagnosis
* Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study and within 90 days after the last dose of atezolizumab
Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study and within 5 months after the last dose of atezolizumab.
* History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator*s judgment
* Any serious medical condition, physical examination finding, or abnormality in clinical laboratory tests that, in the investigator*s judgment, precludes the patient*s safe participation in and completion of the study;Exclusion Criteria Related to Medications
* Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, or any other antibody or drug targeting T-cell co stimulation, with the following exceptions:
Note: Patients enrolled in the prior anti-PD-L1/PD-1 treated cohorts with melanoma may have received prior anti-CTLA-4 treatment or other immunotherapies.
* Treatment with systemic immunostimulatory agents (including but not limited to interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
Note: Prior exposure to alpha-interferons, including Roferon A®, Intron A®, and pegylated interferons, is allowed if the above criteria are met.
* Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to Cycle 1, Day 1
Patients who have received acute and/or low-dose systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea or chronic use of * 10 mg/day of prednisone or dose-equivalent corticosteroid) may be enrolled in the study after discussion with and approval by the Medical Monitor.
The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.;Detailed information about the specific exclusion criteria for Arm A, B, C, D and E can be found on page 81 of the protocol.