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 2 study was 40 KE, which was based on the recommended Phase 2 dose (RP2D) established in the Phase 1a study.

Methods:

ADVANCED-2 (NCT05951179) is a Phase 2, open-label study to evaluate the safety and anti-tumor activity of intravesical instillation of TARA‑002 in adults ≥ 18 years with CIS NMIBC (±Ta/T1) with active disease. Subjects with penicillin allergy, concomitant prostatic or upper tract urothelial involvement or significant urinary incontinence are excluded. The study will include ~127 subjects enrolled in 2 cohorts based on prior BCG experience (Figure 1). Cohort A includes 27 subjects with CIS (±Ta/T1) who are BCG naive, or BCG exposed who have not received BCG for at least 24 months prior to the most recent CIS diagnosis. Cohort B includes 100 subjects with CIS (±Ta/T1) who are BCG unresponsive within 12 months of completion of adequate BCG therapy. The study duration per subject is up to 60 months. Phase 2 is currently open for enrollment.

Results:

The ADVANCED-2 study is ongoing. As of July 12, 2024, 21 subjects were enrolled with a median age of 74. All subjects were non-Hispanic, White with 5 (23.8%) subjects being female. ECOG Score was 0 for 16 (76.2%) and 1 for 5 (23.8%) subjects. Twelve (57.1%) subjects had CIS only, 6 (28.6%) CIS + Ta, and 3 (14.3%) CIS + T1. Overall, 12 (57%) subjects experienced TEAEs (Grade 1: 9 [42.9%]; Grade 2: 5 [23.8%] and Grade 3: 3 [14.3%], of which 4 had drug-related TEAEs (all Grade 1). Two subjects experienced non-drug related SAEs of urinary tract infection, both of which resolved (Table 1). No subjects experienced drug-related SAEs, TEAEs leading to withdrawal, or death. Common AEs reflect urinary tract instrumentation effects, such as bladder spasm, burning sensation, and UTI​. AEs were consistent with the known safety profile of an immune-potentiating drug, such as flu-like symptoms​.

Conclusion:

Preliminary data from the ADVANCED-2 study suggests that TARA-002 appears to be well tolerated, thus demonstrating a favorable tolerability profile for the treatment of BCG Naïve and BCG unresponsive subjects with CIS (±Ta/T1) NMIBC. Enrollment is ongoing and updated data will be shared at the time of the presentation.

Funding: Protara Therapeutics