Phase 1a/b safety study of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer (ADVANCED-1).

Abstract

TPS4620 Background: 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 (consisting of HG Ta, T1, and carcinoma in situ [CIS]). 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) and is approved in Japan and Taiwan for the treatment of several oncology indications. Nonclinical toxicology studies with TARA-002 and nonclinical and clinical studies with OK-432 (a comparable product to 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. The study includes a dose escalation phase (Phase 1a) and a dose expansion phase (Phase 1b). The objective of the study is to evaluate the safety and tolerability of TARA-002, to establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) in the treatment of subjects with HG Ta or CIS ± Ta NMIBC during Phase 1a, and to further assess the safety and preliminary efficacy of TARA-002 in the treatment of subjects with CIS NMIBC with active disease during Phase 1b. For this first-in-human study, stage T1 is excluded. The study includes eligible male and female subjects ≥ 18 years of age who are unable to obtain BCG or have received at least one dose of intravesical BCG or chemotherapy. Those with current or a history of penicillin allergy or current evidence of any condition, therapy, or laboratory abnormality that might confound the results are excluded. The overall study duration for each subject includes 28 days of screening period, 6-week treatment period, and 6-week follow-up period. During the dose escalation phase (1a), up to 18 subjects with HG Ta or CIS ± Ta NMIBC are enrolled. Up to 3 dose levels are tested sequentially with 6 weekly intravesical doses, starting with the lowest dose using a 3+3 design in a dose escalation manner. At the established RP2D, the dose expansion phase (1b) will enroll approximately 12 new subjects with CIS ± Ta NMIBC with active disease and treat in the same manner to further assess the safety and preliminary efficacy of TARA-002. Phase 1a is currently open for enrollment. Clinical trial information: NCT05085977; NCT05085990.