A Study of Atezolizumab Versus Observation as Adjuvant Therapy in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (UC) After Surgical Resection
Condition: Carcinoma, Transitional Cell
MeSH terms: Carcinoma; Carcinoma, Transitional Cell
Intervention: Atezolizumab
Intervention description: Atezolizumab will be administered at a dose of 1200 milligrams (mg).
Intervention MeSH terms: Atezolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 809.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This Phase III, open-label, randomized, multicenter study is to evaluate the efficacy and
      safety of adjuvant treatment with atezolizumab compared with observation in participants with
      muscle-invasive UC who are at high risk for recurrence following resection. Eligible
      participants were randomized by a 1:1 ratio into atezolizumab group or control group.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma)
             of the bladder or upper urinary tract (i.e., renal pelvis or ureters)

          -  For participants treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-4a
             or ypN+ (ypT2-4 or ypN+ for participants with upper urinary tract UC) and M0

          -  For participants who have not received prior neoadjuvant chemotherapy: tumor stage of
             pT3-4a or pN+ (pT3-4 or pN+ for participants with upper urinary tract UC) and M0

          -  Representative formalin-fixed paraffin-embedded tumor specimens from surgical
             resection (i.e., radical cystectomy, nephroureterectomy, or lymph node dissection) in
             paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated
             pathology report, for central testing and determined to be evaluable for tumor
             programmed death-ligand 1 (PD-L1) expression prior to study enrollment

          -  Absence of residual disease and absence of metastasis, as confirmed by a negative
             baseline computed tomography (CT) or magnetic resonance imaging scan of the pelvis,
             abdomen, and chest no more than 4 weeks prior to randomization

          -  Full recovery from cystectomy or nephroureterectomy within 14 weeks following surgery

          -  Eastern Cooperative Oncology Group performance status of less than or equal to (</=) 2

          -  Life expectancy greater than or equal to (>/=) 12 weeks

          -  Adequate hematologic and end-organ function

          -  For women who are not postmenopausal or surgically sterile: agreement to remain
             abstinent or use contraceptive methods that result in a failure rate of less than (<)
             1 percent (%) per year during the treatment period and for at least 5 months after the
             last dose of atezolizumab

        Exclusion Criteria:

          -  Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment

          -  Adjuvant chemotherapy or radiation therapy for UC following surgical resection

          -  Treatment with any other investigational agent or participation in another clinical
             trial with therapeutic intent within 28 days or five half-lives of the drug prior to
             enrollment

          -  Malignancies other than UC within 5 years prior to Cycle 1, Day 1

          -  Pregnancy or breastfeeding

          -  Significant cardiovascular disease

          -  Severe infections within 4 weeks prior to Cycle 1, Day 1

          -  Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day
             1

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
             or any component of the atezolizumab formulation

          -  History of autoimmune disease

          -  Prior allogeneic stem cell or solid organ transplant

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
             chest CT scan

          -  Positive test for human immunodeficiency virus and/or active hepatitis B or hepatitis
             C or tuberculosis

          -  Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1

          -  Prior treatment with cluster of differentiation 137 (CD137) agonists or immune
             checkpoint blockade therapies, including anti-CD40, anti-cytotoxic
             T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1),
             and anti-PD-L1 therapeutic antibodies