S1605: Phase II trial of atezolizumab in BCG-unresponsive nonmuscle invasive bladder cancer.

Radical cystectomy is the standard of care for patients with BCG-unresponsive high risk non-muscle invasive bladder cancer (NMIBC). Based on the reported efficacy of atezolizumab in metastatic urothelial carcinoma and the known expression of PD-L1 expression in NMIBC after BCG therapy, this trial will evaluate the activity of atezolizumab in BCG-unresponsive high risk NMIBC. 


This is a single arm phase II trial testing systemic atezolizumab (1200 mg IV) every 3 weeks for one year in 135 patients with BCG-unresponsive high risk NMIBC. The study will enroll 70 patients with CIS (with or without concomitant Ta/T1) and 65 with Ta/T1 only. Patients with CIS at baseline will undergo mandatory repeat biopsy at 6 months, and all other patients only for suspected recurrence. Patients with persistent CIS, high grade Ta/T1 recurrence or progression to muscle invasive or metastatic disease will be taken off treatment. The co-primary endpoints are: (1) complete response (CR) at 6 months in the CIS subgroup, and (2) event-free survival (EFS) at 18 months in the overall population. A hierarchical approach will be used to test the two co-primary endpoints. Secondary endpoints include duration of CR as well as progression-free, cystectomy-free, bladder cancer-specific, and overall survival in all patients. Response will be correlated to expression of PD-L1 and CD8 by IHC, and to molecular subtypes and immune signatures by RNA-sequencing. If ≥28 (40%) CIS patients respond, the agent will be considered promising. This design has a significance level of 4.6%, and a power of 96%. If the lower bound of the 90% confidence interval of the 18-month EFS excludes 20%, the investigators will conclude the regimen significantly improves EFS relative to historical data (type I error rate 0.05 and statistical power 0.93). Successful completion of this trial could lead to a new treatment paradigm for patients with BCG-unresponsive high risk NMIBC.

DOI: 10.1200/JCO.2018.36.6_suppl.TPS527 Journal of Clinical Oncology 36, no. 6_suppl Published online February 26, 2018.

Peter C. Black, Tangen Catherine, Seth P. Lerner, David James McConkey, M. Scott Lucia, Michael Woods, Trinity Bivalacqua, Wassim Kassouf, Richard Carlton Bangs, Melissa Plets, Ian Murchie Thompson, Parminder Singh 

University of British Columbia, Vancouver, BC, Canada; Fred Hutchinson Cancer Research Center, Seattle, WA; Baylor College of Medicine, Houston, TX; Johns Hopkins School of Medicine, Baltimore, MD; University of Colorado School of Medicine, Aurora, CO; University of North Carolina at Chapel Hill, Chapel Hill, NC; Johns Hopkins Hospital, Baltimore, MD; McGill University Health Centre, Montréal, QC, Canada; SWOG, San Antonio, TX; UT Health Science Center, San Antonio, TX; Mayo Clinic Arizona, Phoenix, AZ