Safety and Pharmacology Study of Atezolizumab Alone and in Combination With Bacille Calmette-Guérin (BCG) in High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) Participants

This is an interventional treatment trial for Bladder Cancer Read More

Inclusion Criteria:

• Histologically confirmed non-muscle-invasive transitional cell carcinoma (TCC) of the bladder with carcinoma in-situ (CIS)
• High-risk NMIBC defined by the following:

BCG-unresponsive NMIBC:

Persistence of high-grade CIS at 6 months following an adequate course of BCG; or Stage/grade progression at 3 months after induction BCG; or Recurrence of high-grade CIS after achieving a disease-free state (i.e., CR) following induction of an adequate course of BCG that occurs less than (<) 6 months after the last exposure to BCG

BCG-relapsing NMIBC:

Recurrence of high-grade CIS after achieving a disease-free state following induction of an adequate course of BCG that occurs greater than or equal to (>/=) 6 months after the last exposure to BCG

Very high-risk (VHR) BCG-naïve NMIBC:

VHR NMIBC, defined as having at least 1 of the following: Multiple and/or large (greater than [>] 3 centimeters [cm]) T1, (HG/G3) tumors; T1, (HG/G3) tumor with concurrent CIS; T1, G3 with CIS in prostatic urethra; Micropapillary variant of non-muscle invasive urothelial carcinoma

• For BCG-unresponsive and BCG-relapsing NMIBC, participants must have received an adequate course of BCG
• Resection of all pTa/pT1 papillary disease
• No prior radiation to bladder or pelvic region
• Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (</=) 2;
• Life expectancy >/=12 weeks
• Adequate hematologic and end-organ function
• Creatinine clearance >/=30 milliliters per minute (mL/min) (calculated using the Cockcroft-Gault formula)
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of study drug. Women must refrain from donating eggs during this same period.
• For men receiving BCG: Agreement to remain abstinent (refrain from sexual intercourse) or use a condom
• Tumor tissue biopsy within 60 days prior to study entry or availability of an archival specimen obtained within 60 days of study screening

Exclusion Criteria:

• Evidence of locally advanced, metastatic, muscle-invasive, and/or extravesical bladder cancer
• Any malignancy within 5 years prior to Cycle 1, Day 1
• History of autoimmune disease, idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or active pneumonitis
• Signs or symptoms of infection within 2 weeks prior to the first dose of study treatment
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to the first dose of study treatment
• Treatment with any approved anti-cancer therapy within 3 weeks prior to the first dose of study treatment
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to the first dose of study treatment
• Pregnant or lactating women, or women intending to become pregnant during the study
• Prior allogeneic stem cell or solid organ transplantation
• Positive test for human immunodeficiency virus (HIV)
• Active hepatitis B or C and/or tuberculosis
• Severe infections within 28 days prior to the first dose of study treatment
• Significant cardiovascular disease
• Major surgical procedure other than for diagnosis within 4 weeks prior to the first dose of study treatment, or anticipation of need for a major surgical procedure during the course of the study
• Administration of a live/attenuated vaccine within 4 weeks prior to the first dose of study treatment, within 5 months following the administration of the last dose of study drug, or anticipation that such a live/attenuated vaccine will be required during the study
• History of prior significant toxicity or intolerance to BCG requiring discontinuation of treatment
• History of prior systemic BCG infection
• History of immunosuppression, or conditions associated with congenital or acquired immune deficiency
• Concurrent febrile illness, urinary tract infection, or gross hematuria
• Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies
• Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of the drug, whichever is shorter, prior to the first dose of study treatment
• Treatment with systemic immunosuppressive medications within 2 weeks prior to the first dose of study treatment, or anticipated requirement for systemic immunosuppressive medications during the trial