Abstract 795TiP
Background
Bacillus Calmette-Guerin (BCG) therapy is the standard of care for high-risk non-muscle invasive bladder cancer after transurethral bladder tumor resection, but disease recurrence or progression is common and subsequent treatment options (eg, cystectomy) are limited. In a phase 1 study, administration of PF-06801591, a monoclonal antibody to programmed cell death protein 1 (PD-1), administered subcutaneously (SC) at 300 mg every 4 wk (Q4W) had an acceptable safety profile and showed clinical activity in patients (pts) with advanced solid tumors, including a dose-expansion cohort of pts with urothelial carcinoma. BCG therapy is associated with increased PD-L1 expression; preclinical and clinical data suggest combining BCG with an inhibitor of PD-1 or its ligand (PD-L1) yields greater antitumor activity vs either agent alone.
Trial design
This randomized, open-label phase 3 study will enroll ∼999 BCG-naïve pts with histologically confirmed high-risk, non-muscle invasive transitional cell carcinoma of the bladder urothelium (T1 tumor, high-grade Ta tumor, or carcinoma in situ [CIS]); no prior PD-1/L1/L2 inhibitors; and no intravesical BCG within 2 y. Pts are randomized 1:1:1 to PF-06801591 + BCG induction and maintenance, PF-06801591 + BCG induction only, or BCG induction and maintenance; stratification factors include presence of CIS and geographic region. Efficacy is assessed by cystoscopy and urine cytology every 12 wk for 2 y and every 24 wk thereafter and by biopsy and imaging as clinically indicated. Primary endpoint is event-free survival; overall survival is a key secondary endpoint. Other secondary endpoints are disease-specific survival, time to cystectomy, time to low-grade disease recurrence, complete response rate and duration of complete response in pts with CIS, safety, and health-related quality of life. This study is currently enrolling in the US, with planned sites in North America, Europe, Asia, and Australia.
Clinical trial identification
NCT04165317.
Editorial acknowledgement
Medical writing support was provided by Joanna Bloom, PhD, of Engage Scientific Solutions, and funded by Pfizer.
Legal entity responsible for the study
Pfizer.
Funding
Pfizer.
Disclosure
G.D. Steinberg: Shareholder/Stockholder/Stock options, Stock or other ownership : Epivax Oncology, Urogen; Advisory/Consultancy, Consulting or advisory role: Heat Biologics, Cold Genesys, PhotoCure, Merck, Roche/Genentech, Ciclomed, Taris Biomedical, MDxHealth, Fidia Farmaceuticals, Urogen, Ferring, Aduro, Boston Scientific, BMS, AstraZeneca, Pfizer, Janssen, Epivax Oncology, Natera, FKD, Ferring, EnGene Bi; Advisory/Consultancy, Clinical Trial Protocol Committee member: Merck, BMS, Janssen, Cold Genesys, Pfizer, PhotoCure, Fidia. N. Shore: Advisory/Consultancy: AstraZeneca, BMS, Ferring, Janssen, Merck, Pfizer, Sanofi-Genzyme, SesenBio; Research grant/Funding (institution): AstraZeneca, BMS, Ferring, Janssen, Merck, Pfizer, Sanofi-Genzyme, SesenBio. R. Cesari: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. J. Vermette: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. K. Pierce: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. J.A. Blake-Haskins: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. S. Hariharan: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. J. Bedke: Advisory/Consultancy: AstraZeneca, Astellas, BMS, Eisai, Ipsen, MSD, Novartis, Roche, EUSA Pharma, Pfizer; Speaker Bureau/Expert testimony: BMS, Eisai, Ipsen, MSD, Novartis, Roche, EUSA Pharma, Pfizer. T. Powles: Research grant/Funding (institution): AstraZeneca, Roche, MSD, Bristol-Myers Squibb; Advisory/Consultancy: Novartis, Bristol-Myers Squibb, Ipsen, Roche, Pfizer, Astellas Pharma, Seattle Geneticis, Merck, MSD, AstraZeneca, Exelixis, and Peloton Therapeutics. All other authors have declared no conflicts of interest.