A Study of MPDL3280A in Combination With Avastin (Bevacizumab) or With Avastin Plus Chemotherapy in Patients With Advanced Solid Tumors

• Safety: Incidence of adverse events [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
• Dose-limiting toxicities/maximum tolerated dose [ Time Frame: 21 days for Arm A and the 28 days following the first administration of MPDL3280A in Arm B ] [ Designated as safety issue: Yes ]

• Pharmacokinetics: Area under the concentration-time curve [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
• Best overall response (tumor assessments according to RECIST criteria) [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
• Objective response rate (complete response + partial response) [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
• Duration of objective response [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
• Progression-free survival [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]

The primary aim of the study is to assess the safety, pharmacology and preliminary efficacy of MPDL3280A [a monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1)] administered with bevacizumab (Arm A) and with bevacizumab plus chemotherapy (Arm B) in patients with advanced solid tumors.

• Drug: MPDL3280A
  multiple escalating doses IV q3w
• Drug: bevacizumab [Avastin]
  15 mg/kg iv q3w
• Drug: chemotherapy
  q2w
• Drug: MPDL3280A
  multiple escalating doses IV q2w
• Drug: bevacizumab [Avastin]
  10 mg/kg q2w

• Experimental: A: MPDL3280A + bevacizumab
  Interventions:

  • Drug: MPDL3280A
  • Drug: bevacizumab [Avastin]
• Experimental: B: MPDL3280A + bevacizumab + chemotherapy
  Interventions:

  • Drug: chemotherapy
  • Drug: MPDL3280A
  • Drug: bevacizumab [Avastin]

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• 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 </=1 prior to study entry, with the exception of alopecia

Exclusion Criteria:

• 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 > 2 weeks prior to Day 1
• Biphosphonate 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 other recombinant human antibodies
• History of autoimmune disease
• History of idiopathic pulmonary fibrosis
• History of HIV or hepatitis C infection; history of hepatitis B is allowed if infection has resolved (absence of HBsAg)
• Severe infections within 4 weeks prior to Day 1, or signs or symptoms of significant infection within 2 weeks prior to Day 1
• Initiation of oral antibiotics < 7 days 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
• Any bevacizumab-specific exclusion criteria