Atezolizumab + intravesical BCG (Bacillus Calmette-Guerin) in high-risk non-muscle invasive bladder cancer (NMIBC) patients: Institutional clinical and translational study (BladderGATE).

Abstract

TPS598 Background: Intravesical Bacillus Calmette-Guerin (BCG) induction + BCG maintenance after transurethral resection (TURBT) is the current standard of care for patients (pt) with high-risk non-muscle invasive bladder cancer (NMIBC). Recurrence rate at 2 years is around 30%, which is clearly unsatisfactory. Programmed death ligand 1 (PD-L1) is a surface glycoprotein that functions as an inhibitor of T-cells and plays a crucial role in suppression of cellular immune response. Atezolizumab is a humanized IgG1 monoclonal antibody targeting PD-L1 and is associated with long-term durable remissions in pts with metastatic urothelial cancer (Powles T. Lancet. 2018). Atezolizumab in combination with standard BCG could be beneficial in pts with NMIBC. BladderGATE (NCT04134000) is a phase Ib-II study aims to evaluate the clinical impact and safety of the combination of Atezolizumab + intravesical BGC (medac strain), including a translational study (microbioma and urobioma) in pts with NMIBC. Methods: Eligible pt have confirmed histopathology of NMIBC, BCG naïve or stopped >3 years ago, WHO PS 0-1, no prior radiation to bladder and adequate hematologic and end-organ function. We propose a de-escalation design to enroll patients to identify DLT and MTD proposed to safety and efficacy expansion cohort. Pt will receive induction BCG, 1 instillation every week (qw) (dose level 0) or BCG, 1/2 instillation qw (dose level -1) + intravenously atezolizumab 1200 mg every 3 w (q3w), during 6 w. After induction, BCG will be administered as maintenance treatment at weeks 12, 24 and 48 and atezolizumab 1200 mg q3w up to 1 year. Pt will be accrued to each dose level in cohorts of 10 pt until the MTD is achieved (the highest dose at which <4 out of 10 pt experience DLT). DLT will be evaluated during induction treatment. Additional pt will be included in the expansion cohort up to 40 pt. DLT and safety profile will be evaluated according to NCI-CTCAE v 5.0 criteria. Recurrence-free survival will be assessed per RECIST 1.1. Tissue, plasma and urine sample will be collected for translational study. Clinical trial information: NCT04134000.