Introduction:

Bladder cancer is the most common malignancy involving the urinary system, resulting in approximately 18,000 deaths each year in the US. Approximately 70% of new urothelial bladder cancer cases are classified as non-muscle invasive bladder cancer (NMIBC). With the current Bacillus Calmette-Guérin (BCG) shortage and limited effective alternate therapies, there continues to be a significant unmet need for treatment options for patients with NMIBC. TARA‑002 is being developed for the treatment of high-grade (HG) NMIBC. TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin. TARA-002 is manufactured using the same master cell bank as OK-432 (Picibanil^®). OK-432 is approved in Japan and Taiwan for the treatment of several oncology indications. Nonclinical toxicology studies with TARA-002 support the starting dose for the planned Phase 1a/b study.

Methods:

ADVANCED-1 is a Phase 1a/b, dose finding, open-label study of intravesical instillation of TARA-002 in adults with HG NMIBC and inability to obtain BCG or have received at least one dose of intravesical BCG or chemotherapy. Eligible subjects will receive weekly doses of TARA-002 for 6 weeks. The study duration includes 28 days screening, 6-week treatment, and 6-week follow-up. During dose escalation phase (1a), up to 18 eligible subjects with HGTa or CIS (± Ta) NMIBC are enrolled to establish the safety, maximum tolerated dose, and recommended Phase 2 dose (RP2D). Up to 3 dose levels are tested sequentially, starting with the lowest dose using a 3+3 design (Figure 1). At the established RP2D, dose expansion phase (1b) will enroll approximately 12 new eligible subjects with CIS (± Ta) with active disease NMIBC to further assess the safety and preliminary efficacy of TARA-002. Phase 1a is currently open for enrollment.

Results:

Conclusion:

Funding: Protara Therapeutics, Inc.