Investigational Cell Therapy Yields Durable Complete Response in BCG-Naïve NMIBC
During treatment with TARA-002, there were no grade 3 or higher TRAEs, and TRAEs did not lead to any treatment discontinuations in patients with BCG-naïve NMIBC.
During treatment with TARA-002, there were no grade 3 or higher TRAEs, and TRAEs did not lead to any treatment discontinuations in patients with BCG-naïve NMIBC.
Updated interim results for TARA-002, an investigational cell therapy, as treatment for patients with carcinoma in situ (CIS) non-muscle invasive bladder cancer (NMIBC) who are Bacillus Calmette-Guérin (BCG)-naïve from the open-label phase 2 ADVANCED-2 trial (NCT05951179) have been announced in a press release from the developer, Protara Therapeutics.1
With a data cutoff of November 7, 2025, among 29 patients who were efficacy-evaluable, BCG-naïve, and received at least 1 dose of TARA-002, the complete response (CR) rate at any time was 72% (n = 21/29 patients). At 6 months, the CR rate was 69% (n = 18/26), and at 12 months, it was 50% (n = 7/14). Among initial responders, 88% of patients (n = 14/16) maintained their response through 6 months, and 100% (n = 3/3) through 12 months.
Reportedly, re-induction therapy was able to salvage most initial non-responders. The rate of re-induced patients converted to a CR at 6 months was 80% (n = 4/5), with 100% of those patients (n = 4/4) maintaining their CR at 12 months.
Regarding safety, most treatment-related adverse events (TRAEs) were grade 1 and transient; no grade 3 or higher TRAEs per study investigators were reported. Further, no TRAEs resulted in treatment discontinuations. The most common TRAEs were dysuria (13%), fatigue (13%), and hematuria (6%).
These results will also be shared in a poster session at the upcoming 26th Annual Meeting of the Society of Urologic Oncology.
Additionally, the developer remains in conversation with the FDA regarding an expansion of the initially agreed-upon registrational pathway forward for TARA-002 beyond the BCG-unresponsive NMIBC population. The developer has also engaged with the FDA to determine how to include patients who were BCG-exposed in clinical trials for TARA-002.
“These encouraging TARA-002 results demonstrate meaningful and durable activity in [patients with] BCG-naïve NMIBC,” stated Mark Tyson, MD, MPH, vice chair for Research and a professor in the Department of Urology at the Mayo Clinic in Phoenix, Arizona, and ADVANCED-2 study investigator, in the press 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-naïve setting.”
A total of 31 patients with NMIBC with CIS who were BCG-naïve and received at least 1 dose of TARA-002 were included in the reported dataset. Treatment consisted of an induction course of 6 weekly intravesical instillations of TARA-002, followed by maintenance of 3 weekly instillations every 3 months. Patients with residual CIS and/or recurrent high-grade Ta disease were permitted to receive re-induction.
ADVANCED-2 also enrolled between 75 and 100 patients with NMIBC with CIS who were BCG-unresponsive.
Eligible patients in the trial were 18 years or older with confirmed histologic confirmation of high-grade NMIBC with CIS, with active disease, and were either BCG-naïve or BCG-exposed and had not received intravesical BCG for at least 24 months prior to the most recent CIS diagnosis.2
Exclusion criteria include a penicillin allergy, central confirmed variant histology, concomitant prostatic or upper tract urothelial involvement per the investigator’s assessment, nodal and metastatic disease, and any history of grade T2 or higher bladder cancer.
Per the developer’s description, TARA-002 is a first-in-class TLR2/NOD2 agonist and novel immunopotentiator derived from inactivated Streptococcus pyogenes; the mechanism of action includes the activation of innate and adaptive immune pathways within the bladder wall.
More interim results from ADVANCED-2, specifically from approximately 25 patients with NMIBC with CIS who are BCG-unresponsive and evaluable after 6 months, will be shared in the first quarter of 2026.
“These positive results continue to support TARA-002’s potential in the NMIBC treatment landscape, and we look forward to finalizing a regulatory pathway for TARA-002 in [patients who are] BCG-Naïve,” Jesse Shefferman, chief executive officer of Protara Therapeutics, said in the release.1 “We remain on track to provide an update on the registrational BCG-unresponsive patient cohort in the ADVANCED-2 trial in the first quarter of 2026 and expect to complete enrollment of this cohort in the second half of 2026.”
References
- 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 03, 2025. Accessed December 03, 2025. https://tinyurl.com/3xuttavk
- 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 03, 2025. https://tinyurl.com/apje8a3h
