A Study of Atezolizumab Administered in Combination With Bevacizumab and/or With Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors

This open-label, Phase Ib study that has six treatment arms is designed to assess the safety, pharmacology and preliminary efficacy of atezolizumab (MPDL3280A; an engineered anti-programmed death-ligand 1 \[PDL1\] antibody) administered with bevacizumab (Arm A) and with bevacizumab plus oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) (FOLFOX) (Arm B), with carboplatin and paclitaxel (Arm C), with carboplatin and pemetrexed (Arm D), with carboplatin and nab-paclitaxel (Arm E), and with nab-paclitaxel (Arm F) in participants with locally advanced or metastatic solid tumors. The study includes dose escalation cohort for establishing the maximum tolerated dose (MTD) or maximum administered dose (MAD) and then expansion cohort will be initiated based on a selected dose level at or below the MTD or MAD.


Eligibility Criteria:
Inclusion Criteria:

General Inclusion Criteria:

* Histologically or cytologically documented advanced solid tumors
* Adequate hematologic and end organ function
* Measurable disease by RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade less than or equal to (\</=) 1 prior to study entry, with the exception of alopecia

Eligible Tumor Types:

Arm A Escalation Cohorts and Arms A and B Biopsy Cohort (Cutaneous/Subcutaneous Lesions)

* Histologically or cytologically documented, incurable or metastatic solid malignancy that has failed all available or acceptable standard therapy for which the participant is eligible Arm A and B Safety Expansion Cohorts, Arm B Escalation Cohorts, and Arm B Biopsy Cohort (Liver Lesions)
* Histologically or cytologically confirmed metastatic colorectal cancer (mCRC). Participants in the Arm A Safety Expansion Cohort must have mCRC for which established therapies have proved ineffective or intolerable. Participants with malignancies other than mCRC within 5 years prior to Day 1 (except for those with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) are not eligible.

Arm A renal cell carcinoma (RCC) Cohort:

- Histologically or cytologically confirmed advanced or metastatic RCC with a clear cell component.

Arm A Tumor Type-Specific Cohort:

Gastric Cancer:

- Histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction for which established therapies have proved ineffective or intolerable. The decision may be made to restrict enrollment to participants with a specified tumor PD-L1 status (e.g., immunohistochemistry \[IHC\] status 0/1 or 2/3)

Ovarian Cancer:

- Measurable/assessable ovarian cancer (defined as epithelial ovarian, fallopian tube, or primary peritoneal cancer) that has progressed less than (\<) 6 months after completing platinum-based therapy. The following histological types are eligible: Adenocarcinoma NOS, clear cell adenocarcinoma, endometriod adenocarcinoma, malignant Brenner's tumour, mixed epithelial carcinoma, mucinous adenocarcinoma, serous adenocarcinoma, transitional cell carcinoma, undifferentiated carcinoma

Bladder Cancer:

* Histologically or cytologically documented locally advanced (T4b, any N; or any T, N 2-3) or metastatic (M1, Stage IV) transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra)
* Participants with mixed histologies are required to have a dominant transitional cell pattern
* Locally advanced bladder cancer must be inoperable based on involvement of pelvic sidewall or adjacent viscera (clinical stage T4b) or bulky nodal metastasis (N2-N3)
* Disease progression during or following treatment with at least one platinum-containing regimen (e.g., GC, MVAC, CarboGem, etc.) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence

Cervical Cancer:

* Persistent or recurrent squamous cell carcinoma of the cervix (including adenosquamous tumors)

Arms C, D, and E Cohorts:

- Histologically or cytologically documented Stage IIIB (not eligible for definitive chemoradiotherapy), Stage IV, or recurrent non-small cell lung cancer (NSCLC)

Arm F Cohort:

* Histologically confirmed estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor (HER)-negative (triple-negative) adenocarcinoma of the breast that has been treated with systemic cytotoxic therapy. Locally recurrent disease must not be amenable to resection with curative intent
* Participants with tumors amenable to excisional, punch, or core needle biopsy are eligible for a separate biopsy expansion cohort

Tumor molecular status:

Arm A safety expansion cohort

- Up to 10 participants with CRC and high microsatellite instability (MSI-H) may be enrolled

Exclusion Criteria:

General Exclusions

* Any approved anti-cancer therapy, including chemotherapy, hormonal therapy, radiotherapy, or herbal therapy intended as anti-cancer therapy, within 3 weeks prior to initiation of study treatment; the following are allowed: hormonal therapy with gonadotropin-releasing hormone agonists or antagonists for prostate cancer, hormone-replacement therapy, and palliative radiotherapy for bone metastases greater than (\>) 2 weeks prior to Day 1
* Bisphosphonate therapy for symptomatic hypercalcemia
* Known clinically significant liver disease
* Known primary central nervous (CNS) malignancy or active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
* Pregnant or lactating women
* Known hypersensitivity to Chinese hamster ovary cell products or any component of the atezolizumab formulation
* History of autoimmune disease, idiopathic pulmonary fibrosis, human immunodeficiency virus (HIV), hepatitis B or C infection; history of hepatitis B is allowed if infection has resolved (absence of hepatitis B surface antigen \[HBsAg\])
* Severe infections within 4 weeks prior to Day 1, or signs or symptoms of significant infection within 2 weeks prior to Day 1
* Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
* History of myocardial infarction, unstable angina stroke or transient ischemic attack within 6 months prior to Day 1
* Administration of a live, attenuated vaccine within 4 weeks before Day 1 or anticipation that such a live attenuated vaccine will be required during the study Bevacizumab-Specific Exclusions (Arms A and B) Exclusion Criteria Unique to Arm A RCC Cohort
* Any prior systemic treatment (including tyrosine kinase inhibitors, antibody therapy, immunotherapy, chemotherapy, hormonal therapy, or investigational therapy) for RCC. All treatments, neo-adjuvant, adjuvant, or for locally advanced or metastatic RCC are not permitted

Arm A Tumor Type-Specific Cohort:

Gastric Cancer:

- Prior approved or experimental anti-vascular endothelial growth factor or its receptor (VEGF/VEGFR) therapy (including, for example, bevacizumab or nintedanib). The decision may be made to allocate a specified number of slots to participants who have received prior anti-VEGF/VEGFR therapy

Ovarian Cancer:

* Refractory disease
* History of bowel obstruction
* \>2 prior anticancer regimens
* Prior approved or experimental anti-VEGF/VEGFR therapy (including, for example, bevacizumab or nintedanib)

Cervical Cancer:

- \> 2 prior cytotoxic regimens, not including prior cisplatin-based chemotherapy concomitantly administered with primary pelvic radiation

Exclusion Criteria Unique to Arm B:

* Prior treatment with an oxaliplatin-containing regimen. Oxaliplatin \>12 months prior to the diagnosis of metastatic disease is permitted.
* Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene polymorphism predisposing the participant for 5-FU toxicity

Exclusion Criteria Unique to Arms C, D, and E:

* Prior chemotherapy for locally advanced or metastatic NSCLC
* For participants who received prior adjuvant/neo-adjuvant chemotherapy or chemoradiation for NSCLC, a treatment-free interval \>6 months between the last treatment administration and the date of recurrence in required
* Participants with a known epidermal growth factor receptor (EGFR) sensitizing mutation must have experienced disease progression during or after treatment with an approved EGFR tyrosine kinase inhibitor
* Participants with a known anaplastic lymphoma kinase (ALK) fusion oncogene must have experienced disease progression during or after treatment with crizotinib
* For Arm D (carboplatin + pemetrexed), squamous cell histology or evidence of mixed NSCLC histology with a predominance of the squamous cell type
* For Arm D (carboplatin + pemetrexed), inability to discontinue treatment with non-steroidal anti-inflammatory drugs (NSAIDs) for 5 days

Exclusion Criteria Unique to Arm F:

* Prior therapy with more than two cytotoxic regimens for metastatic or locally advanced triple-negative breast cancer (TNBC)
* Treatment with a taxane-containing regimen within 6 months before enrollment