Durable Responses With Novel Cell Therapy TARA-002 in BCG-Naive NMIBC

The investigational cell therapy TARA-002 demonstrated durable clinical benefits in Bacillus Calmette-Guérin (BCG)-naive patients with carcinoma in situ (CIS) non–muscle invasive bladder cancer (NMIBC), according to interim data from the phase 2 ADVANCED-2 trial (NCT05951179).¹

This latest report detailing the data of 29 efficacy-evaluable, BCG-naive patients showed that as of a November 7, 2025 data cutoff, the complete response (CR) rate at any time was 72%. At 6 and 12 months, the CR rates were 69% (n = 18/26) and 50% (n = 7/14), respectively.

On top of the high rates of response in this cohort, most responses were highly durable through the 6- and 12-month landmarks. Of those who responded initially, responses were maintained through 6 months in 88% (n = 14/16) and 100% (n = 3/3) through 12 months. Re-induction therapy with TARA-002 successfully salvaged most patients who had not responded initially (80%; n = 4/5), converting to CRs at 6 months. All 4 of these responses were maintained through 12 months.

Moreover, the agent demonstrated a favorable safety profile in the entirety of BCG-naive patients included in the analysis (n = 31), in line with earlier reports.² The most frequently occurring treatment-related adverse events (TRAEs) were dysuria (13%), fatigue (13%), and hematuria (6%). TRAEs were mainly grade 1 and transient; there were no grade 3 or greater TRAEs or treatment discontinuations due to TRAEs.

“These encouraging TARA-002 results demonstrate meaningful and durable activity in BCG-[n]aive patients [with NMIBC],” said Mark Tyson, MD, MPH, department of Urology, Mayo Clinic and study investigator in a news release.¹ “The clinically meaningful response rates at [6] and 12 months, coupled with a favorable safety and tolerability profile and simple administration that is even more streamlined than BCG, make TARA-002 a compelling potential treatment option in the BCG-[n]aive setting.”

The positive data in this BCG-naive patient population fall in line with ongoing discussions between the FDA and sponsor Protara Therapeutics regarding potential expansion of TARA-002’s current registrational strategy for BCG-unresponsive patients to also include BCG-naive patients.

Rationale and Course of Development

TARA-002 is a novel, intravesically administered cell therapy in development for the treatment of NMIBC and lymphatic malformations, the latter for which the agent previously earned a rare pediatric disease designation from the FDA.

As an immunopotentiator derived from Streptococcus pyogenes, TARA-002’s mechanism of action is proposed to activate innate and adaptive immune systems within the bladder wall as well as directly induce tumor cell death, yielding a robust, local antitumor effect. The agent was developed from the same master cell bank as the immunopotentiatior OK-432 (Picibanil), which is approved for treatment of lymphatic malformations in Japan, Taiwan, and the Republic of Korea.

TARA-002’s intravesical instillation mode for delivery as monotherapy makes it a welcome and anticipated addition to the NMIBC treatment landscape,³ particularly for those who are BCG-unresponsive or unable to receive BCG. Accordingly, the ADVANCED-2 trial is investigating its therapeutic potential in both patient populations.

The ADVANCED-2 trial is a phase 1b/2, open-label, multicenter trial evaluating the safety and efficacy of TARA-002 in high-grade NMIBC.⁴ Now in its phase 2 stage, the study is currently accruing between 75 to 100 adult patients with NMIBC with CIS for enrollment into its BCG-unresponsive cohort alongside its parallel BCG-naive (n = 31) cohort, estimating enrollment completion by the latter half of 2026. Enrolled patients have received an induction course consisting of 6 weekly intravesical instillations of TARA-002, followed by maintenance therapy of 3 weekly instillations every 3 months to evaluate long-term outcomes.

The evaluation of TARA-002 in phase 2 was based on the successful completion of the preceding ADVANCED-1 trial (NCT05085977), a phase 1 dose-escalation study that assessed the safety and toxicity of the agent.⁵ Results from this study showed that TARA-002 was well tolerated and exhibited early antitumor activity.

The Road Forward: A Forthcoming Controlled Trial

Beyond the ADVANCED-2 trial, the FDA has provided positive feedback to Protara Therapeutics on the proposed registrational design for a controlled trial of TARA-002 in BCG-naive patients, although discussions regarding including BCG-exposed patients remain ongoing.

Specifically, the FDA indicated that intravesical chemotherapy would be an acceptable comparator to TARA-002. The parties have also aligned on a primary end point of 6-month CR rate and key secondary end point of duration of response, allowing for a more robust investigation into the durability of benefit reported in this interim analysis.

REFERENCES

1. Protara Therapeutics announces updated interim data from Phase 2 ADVANCED-2 trial of TARA-002 in BCG-naïve NMIBC patients. News release. Protara Therapeutics. December 3, 2025. Accessed December 3, 2025. https://tinyurl.com/5434husu

2. Mazzarella B, Jayram G, Shore N, et al. ADVANCED-2: Phase 2 open-label study to evaluate safety and anti-tumor activity of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer. Urol Oncol – Semin Ori. 2025;43(3):48. doi:10.1016/j.urolonc.2024.12.122

3. Wiesen B, Hargis P, Flores H, et al. Updated review on novel therapies and ongoing clinical trials for high-risk non-muscle invasive bladder cancer. Front Oncol. 2025;15:1519428. Published 2025 Feb 21. doi:10.3389/fonc.2025.1519428

4. Safety and efficacy study of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer (ADVANCED-2). ClinicalTrials.gov. Updated November 25, 2025. Accessed December 3, 2025. https://clinicaltrials.gov/study/NCT05951179

5. Safety and toxicity study of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer (Phase 1a) (ADVANCED-1). ClinicalTrials.gov. Updated January 27, 2025. Accessed December 3, 2025. https://clinicaltrials.gov/study/NCT05085977