IBCN 2022: Innovation and Novel Approach To the Treatment of NMIBC and MIBC

(UroToday.com) In one of the Industry Meets IBCN sessions, Janssen presented the history and scientific rationale behind the trials designed for TAR200 and TAR210. TAR-200 is an innovative drug delivery system enabling sustained local drug delivery within the bladder. The TAR-200 platform is a bi-oval shaped, dual lumen silicone tube that allows for sustained rug delivery into the bladder over an extended period without any appreciable systemic exposure or associated AEs. This delivery mechanism has been tested previously through a rapid, in-office procedure using an urinary catheter-like inserter. Once released into the bladder, it curls into the a pretzel shape and dwells within the bladder without causing untoward side-effects or sensations. A proof-of-principle phase 1 trial - TAR-200-101 (NCT02722538) – demonstrated safety and tolerability in patients with cT2a-3b N0-1 M0 urothelial carcinoma, who refused or were ineligible to receive cisplatin-based combination chemotherapy. In 4/20 experienced a complete pathologic response at the time of radical cystectomy, while 10/20 experienced downstaging. ¹  In another study using TAR-200 in MIBC patients refusing radical cystectomy (TAR-200-103), PFS following TAR-200 delivery at 12mo was 67.7% and median OS was 20.1 months.

Based on the promising data from the TAR-200-101 and TAR-200-103, as well as a conjectured mechanistic synergism between the immunogenic cell death caused by intravesical treatment with immune checkpoint blockade, Janssen has launched 3 different trials spanning many disease spaces within bladder cancer. In the SunRISe-1 trial, patients with BCG unresponsive CIS are randomized 1:2:1 to TAR-200 alone vs. TAR-200 + cetrelimab (PD-1 inhibitor) vs. cetrelimab alone. The trial aims to evaluate CR at any time point, as assessed by bladder mapping biopsy at an early time point, along with for cause biopsies for suspicious lesions found on routine cystoscopic surveillance. The Janssen group stressed the importance of response durability, and will be assess the 12mo duration of CR as a secondary endpoint. The SunRISe-2 trial builds upon the success of TAR-200-101 and TAR-200-103 and attempts to answer the question whether TAR-200 + cetrelimab will prevent disease progression in MIBC patients refusing to undergo radical cystectomy. The bladder-intact event-free survival will be tested against a control arm enrolling patients being treated with standard chemoradiotherapy, suing an investigator’s choice of radio-sensitizing chemotherapy. Finally, in the SunRISe-4 trial, pathologic complete response rates seen at radical cystectomy will be compared between patients treated neoadjuvantly with TAR-200 + cetrelimab vs. cetrelimab alone.

Presented by: Sam Spiegelman (Janssen); Trinity J. Bivalacqua, MD, PhD, Urology, University of Pennsylvania

Written by: Roger Li, Urologic Oncologist, Moffitt Cancer Center, during the International Bladder Cancer Network Annual Meeting, September 28-October 1, 2022, Barcelona, Spain