Introduction:

Bacillus Calmette-Guérin (BCG) remains the only FDA-approved front-line treatment for high-grade (HG) non-muscle invasive bladder cancer (NMIBC), including carcinoma in situ (CIS), high-grade (HG) Ta and HGT1. Persistent global supply shortages of BCG have prohibited many patients from accessing this critical therapy. There continues to be a significant unmet need for treatment options for patients with NMIBC, and this need is more pronounced in patients who are ineligible to receive BCG (contraindicated), cannot tolerate BCG, do not have access to BCG, or refuse BCG. TARA-002 is a lyophilized biological preparation for intravesical instillation containing inactivated cells of Streptococcus pyogenes (Group A, type 3) Su strain. TARA-002 rapidly enters cancer cells, activating TLR2 and NOD2 to trigger innate immunity, inflammation, and potential immunogenic cell death. This abstract presents interim efficacy and safety data of TARA-002 from the BCG-naïve cohort of the ADVANCED-2 study (NCT05951179).

Methods:

ADVANCED-2 is a Phase 2, open-label study to evaluate the safety and efficacy of intravesical TARA‑002 in adults ≥ 18 years with HG-NMIBC CIS (± Ta/T1). This BCG-naïve cohort includes participants who were never exposed to BCG and those who have not received intravesical BCG for at least 24 months prior to the most recent CIS diagnosis. Key exclusion criteria include penicillin allergy; history of ≥ T2 bladder cancer, nodal, or metastatic disease; and concomitant prostatic or upper tract urothelial involvement. Each participant is treated with TARA-002 to receive induction (6 weekly doses), reinduction (if persistent disease at 3 months) and maintenance (through 24 months). Response is assessed every 3 months for 2 years. Long-term follow-up is conducted up to 60 months. Safety is monitored throughout the study. The primary endpoint is high-grade complete response (CR) at any time. The key secondary endpoint is duration of response.

Results:

The ADVANCED-2 study is ongoing. As of July 15, 2025, 31 BCG-naïve participants have been enrolled. Majority of BCG-naïve participants are white (94%, 29 of 31), male (81%, 25 of 31), and non-Hispanic (90%, 28 of 31). The median age is 71 years. The majority of participants had a baseline ECOG score of 0 (84%, 26 of 31) and baseline diagnoses of CIS only (58%, 18 of 31). TARA-002 demonstrates a 75.0% (21 of 28) HG CR at any time in evaluable participants. The 6-month CR is 63.6% (14 of 22), the 9-month CR is 58.3% (7 of 12), and the 12-month CR is 40.0% (4 of 10). Most treatment-emergent adverse events (TEAEs) were mild and transient. No participants experienced drug-related serious AEs (SAEs) or drug-related TEAEs leading to withdrawal or death.

Conclusion:

Preliminary data suggest that TARA-002 monotherapy is well-tolerated and produces clinically meaningful rates of initial and complete response coupled with durability of response in BCG-naïve HG NMIBC with CIS (± Ta/T1) through twelve months of treatment. Updated efficacy and safety data will be provided based on evaluable time points at the time of the presentation.

Funding: Protara Therapeutics, Inc.