A Study of MOXR0916 in Combination With Atezolizumab Versus Atezolizumab Alone in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Therapy
Condition: Urothelial Carcinoma
MeSH terms: Carcinoma; Carcinoma, Transitional Cell
Intervention: MOXR0916; Atezolizumab
Intervention description: MOXR0916, 300 milligram (mg) by intravenous (IV) infusion on Day 1 of each 21-day cycle.; Atezolizumab, 1200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle.
Intervention MeSH terms: Atezolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Masking description: The study design has been amended in that the study blinding will not be maintained.
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase II, multicenter, randomized, placebo-controlled, double-blind study to
      evaluate the safety and efficacy of MOXR0916 in combination with atezolizumab versus placebo
      and atezolizumab in participants with locally advanced or metastatic urothelial carcinoma
      (UC) who have not received prior systemic therapy in the locally advanced/metastatic setting
      and who are ineligible to receive cisplatin-based therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age >= 18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status of <= 2

          -  Life expectancy >= 12 weeks

          -  Histologically or cytologically confirmed locally advanced or metastatic urothelial
             carcinoma (UC)

          -  Availability of a representative formalin-fixed paraffin-embedded tumor specimen

          -  No prior systemic therapy for inoperable locally advanced or metastatic UC

          -  Ineligible for cisplatin-based chemotherapy as defined by any one of the following
             criteria: Impaired renal function (glomerular filtration rate [GFR] > 30 but < 60
             milliliter/minute [mL/min]); National Cancer Institute Common Terminology Criteria for
             Adverse Events (NCI CTCAE) version (v) 4.0 Grade >= 2 audiometric hearing loss (of 25
             Decibel at two contiguous frequencies or more severe); NCI CTCAE v 4.0 Grade >= 2
             peripheral neuropathy; ECOG Performance Status of 2

          -  Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1

          -  Adequate hematologic and end-organ function

        Exclusion Criteria:

          -  Significant cardiovascular disease

          -  Known clinically significant liver disease

          -  Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3
             weeks prior to initiation of study treatment

          -  Prior treatment with CD137 or OX40 agonists, anti-cytotoxic T-lymphocyte-associated
             protein (CTLA4), anti-programmed death-1 (PD-1), anti- programmed death-ligand 1
             (PD-L1), anti-CD-27, anti- glucocorticoid-induced tumor necrosis factor receptor
             (GITR) therapeutic antibody or pathway-targeting agents

          -  Untreated central nervous system (CNS) metastases or active (progressing or requiring
             corticosteroids for symptomatic control) CNS metastases

          -  Any history of leptomeningeal disease

          -  Malignancies other than UC within 5 years prior to Cycle 1, Day 1

          -  History of autoimmune disease

          -  History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or
             evidence of active pneumonitis on screening chest computed tomography scan

          -  Active hepatitis B and C virus infection

          -  Positive HIV test at screening

          -  Active tuberculosis

          -  Prior allogeneic stem cell or solid organ transplantation