A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 2)
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: Atezolizumab
Intervention description: Atezolizumab 1200 mg given by IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria/loss of clinical benefit or unmanageable toxicity.
Intervention MeSH terms: Atezolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 310.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: anti-PD-L1; PD-L1; MPDL3280A; PD-1; bladder cancer; atezolizumab; Tecentriq

Summary:

      This Phase II, single-arm study is designed to evaluate the effect of atezolizumab treatment
      in participants with locally advanced or metastatic urothelial bladder cancer. Participants
      will be enrolled into 1 of 2 cohorts. Cohort 1 will consist of participants who are
      treatment-naïve and ineligible for cisplatin-containing chemotherapy. The results of Cohort 1
      are reported separately (NCT02951767). Cohort 2 (reported here) will contain participants who
      have progressed during or following a prior platinum-based chemotherapy regimen. Participants
      in both cohorts will be given a 1200 milligrams (mg) intravenous (IV) dose of atezolizumab on
      Day 1 of 21-day cycles. Treatment of participants in Cohort 1 will continue until disease
      progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or
      unmanageable toxicity. Treatment of participants in Cohort 2 will continue until loss of
      clinical benefit or unmanageable toxicity.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically documented locally advanced or metastatic transitional
             cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder,
             urethra)

          -  Representative tumor specimens as specified by the protocol

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Life expectancy greater than or equal to (>=) 12 weeks

          -  Measurable disease, as defined by RECIST v1.1

          -  Adequate hematologic and end organ function

        Cohort 2-Specific Inclusion Criteria

          -  Disease progression during or following treatment with at least one
             platinum-containing regimen (e.g., gemcitabine and cisplatin [GC], methotrexate,
             vinblastine, doxorubicin, and cisplatin [MVAC], CarboGem, etc.) for inoperable locally
             advanced or metastatic urothelial carcinoma or disease recurrence.

          -  A regimen was defined as participants receiving at least two cycles of a
             platinum-containing regimen. Participants who had received one cycle of a
             platinum-containing regimen but discontinued due to Grade 4 hematologic toxicity or
             Grade 3 or 4 non-hematologic toxicity could also be eligible.

          -  Participants who received prior adjuvant/neoadjuvant chemotherapy and progressed
             within 12 months of treatment with a platinum-containing adjuvant/neoadjuvant regimen
             were considered as second-line participants.

        Exclusion Criteria:

          -  Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment

          -  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 as determined by computed
             tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and
             prior radiographic assessments

          -  Leptomeningeal disease

          -  Uncontrolled tumor-related pain

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently)

          -  Uncontrolled hypercalcemia (greater than [>] 1.5 millimoles per liter [mmol/L] ionized
             calcium or Ca > 12 milligrams per deciliter [mg/dL] or corrected serum calcium > upper
             limits of normal [ULN]) or symptomatic hypercalcemia requiring continued use of
             bisphosphonate therapy or denosumab

          -  Malignancies other than urothelial bladder 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 or incidental prostate cancer

          -  Pregnant and lactating women

          -  History of autoimmune disease

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
             chest CT scan

          -  Serum albumin less than (<) 2.5 grams per deciliter (g/dL)

          -  Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or
             hepatitis C or tuberculosis

          -  Severe infections within 4 weeks prior to Cycle 1, Day 1

          -  Significant cardiovascular disease

          -  Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day
             1

          -  Prior allogeneic stem cell or solid organ transplant

          -  Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1

          -  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 patient at high risk from treatment
             complications

          -  Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
             anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed
             death-1 receptor (anti-PD-1), and anti-programmed death-ligand 1 (anti-PD-L1)
             therapeutic antibodies