Assistant Professor University of Rochester Medical Center
Introduction: Bladder cancer is the most common malignancy involving the urinary system, resulting in ~18,000 US deaths/year; ~70% of new urothelial bladder cancer cases are classified as non-muscle invasive bladder cancer (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 (HG) NMIBC. 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. We report on the design and progress of study ADVANCED-1 (NCT05085977; NCT05085990). Methods: ADVANCED-1 is a P1a/b, dose finding, open-label study of intravesical TARA-002 in adults = 18 yrs with HG NMIBC. The purpose of 1a dose escalation is to establish the maximum tolerated dose (MTD) and recommended P2 dose (RP2D) for the treatment of HGTa or CIS NMIBC (±Ta). The purpose of 1b dose expansion is to evaluate the anti-tumor activity and safety of induction ± re-induction of TARA-002 for the treatment of CIS NMIBC (±Ta/T1) with active disease at the established RP2D. 1a includes up to 18 subjects at 3 doses (10 KE, 20 KE, 40 KE) in a 3+3 design; 1b includes ~102 subjects enrolled in 2 cohorts based on prior BCG experience: Cohort A includes subjects unable to obtain BCG and BCG-exposed subjects who have not received BCG in the last 24 months; Cohort B includes subjects with BCG unresponsive CIS. Those with a history of penicillin allergy or current evidence of any condition, therapy, or laboratory abnormality that might confound the results are excluded. The duration is 12 weeks per subject for 1a (includes induction), 6 months per subject for 1b-Cohort A (includes induction, reinduction [if applicable]), and 24 months per subject for 1b-Cohort B (includes induction; reinduction [if applicable]; maintenance until 18 months). Results: In the 1a, at the time of writing, 3 subjects (2 female; 1 male) 66-80 yrs have completed treatment with TARA-002 at 10 KE with no dose limiting toxicities (DLT), and enrollment at 20 KE is ongoing. Conclusions: The 1a will establish the RP2D of TARA-002 and 1b will provide further evidence of anti-tumor activity and safety of TARA-002. SOURCE OF Funding: Protara Therapeutics, Inc. funded this study
