a study of atezolizumab in participants with locally advanced or metastatic urothelial bladder cancer (cohort 1)

Conditions: Bladder Cancer

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 (reported here) will consist of participants who are treatment-naïve and ineligible for cisplatin-containing chemotherapy. cohort 2 will contain participants who have progressed during or following a prior platinum-based chemotherapy regimen. the results of the second cohort are reported separately (nct02108652). 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 1-specific inclusion criteria * no prior chemotherapy for inoperable locally advanced or metastatic or recurrent urothelial carcinoma * ineligible for cisplatin-based chemotherapy due to one of the following: impaired renal function, a hearing loss of 25 decibels (db) at two contiguous frequencies, grade 2 or greater peripheral neuropathy, or ecog performance score of 2 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

Keywords: anti-pd-l1 pd-l1 mpdl3280a pd-1 bladder cancer atezolizumab tecentriq