Introduction:

Bladder cancer is the most common malignancy involving the urinary system, resulting in ~18,000 deaths each year. It is the 6^th most common cancer in the United States, with non-muscle invasive bladder cancer (NMIBC) representing approximately 80% of bladder cancer diagnoses. With the current Bacillus Calmette-Guérin (BCG) shortage and limited effective alternative therapies, there remains a significant unmet need for treatment options for patients with NMIBC. TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin and is being developed for the treatment of high-grade NMIBC. TARA-002 is manufactured using the same master cell bank as OK-432, which is approved in Japan and Taiwan for the treatment of several oncology indications. The dose for the Phase 1b/2 study is 40 KE, which is based on the recommended Phase 2 dose (RP2D) established in the Phase 1a study.

Methods:

ADVANCED-2 (NCT05951179) is a Phase 1b/2, dose-expansion, open-label study of intravesical instillation of TARA-002 in adults ≥18 years with CIS NMIBC (±Ta/T1). The purpose of this study is to assess the safety and anti-tumor activity of TARA‑002, at the established RP2D, in the treatment of subjects with CIS (±Ta/T1) with active disease. The key inclusion and exclusion criteria are summarized in Table 1. The study includes ~102 subjects enrolled in 2 cohorts based on prior BCG experience (Figure 1). Cohort A includes 27 subjects with CIS (±Ta/T1) who are unable to obtain intravesical BCG or have not received it for 24 months prior to CIS diagnosis. Cohort B includes 75 subjects with CIS (±Ta/T1) BCG unresponsive after completion of adequate BCG therapy. The study duration per subject is 6 months for Cohort A and 24 months for Cohort B. Phase 1b/2 is currently open for enrollment.

Results:

Conclusion:

Funding: Protara Therapeutics, Inc.