Treatment With Investigational TAR-200 Demonstrates Promising Results With BCG-Unresponsive HR NMIBC

At the 25^th Annual Meeting of the Society of Urologic Oncology, Dr. Siamak Daneshmand, Professor of Urology (Clinical Scholar) and Director of Clinical Research of the Keck School of Medicine at the University of Southern California, presented additional results on the safety and tolerability of monotherapy with the investigational agent TAR-200 in a cohort from the ongoing phase 2B SunRISe-1 trial (SR-1: NCT04640623).

The SunRISe-1 trial is a randomized, parallel-assignment, open-label Phase 2 clinical study evaluating the safety and efficacy of TAR-200 combined with anti-programmed cell death (PD-1) drug, cetrelimab, TAR-200 alone, or cetrelimab alone in BCG-unresponsive high-risk non-muscle-invasive bladder cancer (HR NMIBC) carcinoma in situ (CIS) patients who are either ineligible for or have chosen not to undergo radical cystectomy.

Dr. Daneshmand and colleagues indicated, “Treatment options that are safe, bladder preserving, and effective for patients with BCG-unresponsive HR NMIBC are limited. TAR-200, a novel targeted releasing system, is designed to provide sustained release of gemcitabine in the bladder over many days.”

The trial participants were randomized into one of four cohorts: cohort 1 received TAR-200 combined with cetrelimab, cohort 2 received TAR-200 alone, cohort 3 received cetrelimab alone, and cohort 4 received TAR-200 alone with papillary disease only.

Preliminary results presented at the May 2024 American Urological Association Annual Meeting demonstrated a promising complete response (CR) rate of 83% and durable responses in patients with BCG-unresponsive HR NMIBC treated with TAR-200.

In this presentation, researchers revealed that as of May 13, 2024, 85 CIS patients (average age 71 years, range 40-88 years; 33% with concomitant papillary disease) received TAR-200 monotherapy. The CR rate was 84%, with a 99% TAR-200 insertion success rate and a median indwelling duration of 22 days.

Moreover, 84% of patients reported treatment-related adverse events (TRAEs), particularly grade 1-2 lower urinary tract-related symptoms. In addition, 39% experienced pollakiuria, 35% experienced dysuria, 20% presented with urinary tract infections, 18% presented with micturition urgency, and 14% presented with hematuria.

The average duration of TRAE resolution was 22 days, with grade 3-4 TRAEs occurring in 9% of patients and serious TRAEs in 6%, resulting in treatment discontinuation in five patients due to noninfective cystitis (n=3), pollakiuria (n=1), and urinary retention (n=1), within 4.8 months of initial treatment. However, there were no reports of treatment-related mortalities.

Based on the data, the researchers concluded that monotherapy was well tolerated, with a high rate of insertion success and an average indwelling interval of 22 days. Moreover, the most frequently reported lower urinary tract TRAEs were manageable and resolved swiftly.

“TAR-200 has a promising safety and efficacy profile as a local, bladder-sparing treatment in HR NMIBC unresponsive to BCG. These results support the continued investigation of TAR-200 in BCG-unresponsive HR NMIBC.” wrote Dr. Daneshmand and colleagues.

Reference

Daneshmand S, Zainfeld D, Pieczonka C et al. Safety and Tolerability of TAR-200 Monotherapy in Patients with Bacillus Calmette–Guérin (BCG)-Unresponsive High-Risk Non–Muscle-Invasive Bladder Cancer (HR NMBIC) in SUNRISE-1.  Poster #135. Presented at the 25th Annual Meeting of the Society of Urologic Oncology; December 4-6, 2024; Dallas, Texas.