Phase 2 data support TARA-002 activity in BCG-naïve NMIBC

Treatment of BCG-naïve, high-grade non-muscle invasive bladder cancer (NMIBC) with the investigational treatment TARA-002 was high complete response (CR) rate at any time as well as favorable safety outcomes, according to data from the phase 2 ADVANCED-2 trial (NCT05951179) presented at the 2025 Society of Urologic Oncology Annual Meeting in Phoenix, Arizona.¹

In their poster, the investigators described TARA-002 as “a first-in-class TLR2/NOD2 agonist and novel immunopotentiator derived from inactivated Streptococcus pyogenes with a mechanism of action that includes the activation of innate and adaptive immune pathways within the bladder wall.”

In an interview with Urology Times, study investigator Mark D. Tyson II, MD, MPH, discussed the background for the study.

“There's a BCG shortage. BCG is a very good drug. It’s highly effective, reasonably well tolerated, and cheap, but it's in short supply...TARA-002 is the opposite [in terms of supply]. I’m told by the company executives that there is a lot of product, and so if there's a signal here, then this is something we can pivot to quickly and use in this space,” said Tyson, a urologist oncologist at Mayo Clinic in Phoenix, Arizona.

Earlier this year, at the 2025 American Urological Association Annual Meeting in Las Vegas, Nevada, investigators reported data from ADVANCED-2 evaluating TARA-002 in patients with BCG-unresponsive and BCG-naïve NMIBC. That study indicated that treatment with TARA-002 was associated with a 100% high-grade CR at any time in BCG-unresponsive participants.² At 6 months, the CR rate in BCG-unresponsive patients was 100%; at 9 months, the CR rate was 80%; and at 12 months was 67%.³

Cohort A of ADVANCED-2 is an ongoing, open-label study evaluating TARA-002 in adults with high-grade NMIBC with carcinoma in situ (CIS) plus or minus Ta/T1 disease who have active disease and are BCG naïve, which was defined as having never been exposed to BCG or having not received intravesical BCG for at least 24 months. The primary end point was high-grade CR at any time per central pathology, and the key secondary end point was duration of response at 12 months.

Following an induction phase comprising 6 weekly instillations of TARA-002, patients underwent maintenance treatment for months 3 to 24. Treatment was re-induced if there was persistent disease at 3 months.

The study included a total of 31 patients; median age was 71.0 years. Twenty-five (80.6%) patients were male, and 29 (93.5%) were White.

The investigators reported a high-grade CR rate at any time of 72.4% (21 of 29 patients); high-grade CR rate was 69.2% at month 6 (18 of 26 patients) and 50.0% at month 12 (7 of 14 patients). Of the initial responders, 87.5% (14 of 16 patients) maintained their response through month 6, and 100% (3 of 3 patients) maintained their response through month 12. With initial non-responders who underwent re-induction, 80% (4 of 5 patients) converted to a CR by month 6, and all responders maintained a CR through month 12 (4 of 4 patients).

Regarding safety, no grade 3 or higher treatment-related adverse events (AEs) were reported. The most commonly reported TRAEs were fatigue, dysuria, and hematuria. No serious AEs related to TARA-002 were observed, and there were no TRAEs leading to withdrawal from the study.

“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 BCG-naïve patients,” said Jesse Shefferman, CEO of Protara Therapeutics in a news release from the company. “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.”⁴

REFERENCES

1. Tyson M, Jayram G, Doronina M, et al. ADVANCED-2: Preliminary efficacy and safety data in BCG-naïve participants with high-grade non-muscle invasive bladder cancer. Presented at: Society of Urologic Oncology Annual Meeting; December 2-5, 2025; Phoenix, Arizona. Abstract 149. https://suo-abstracts.secure-platform.com/a/gallery/rounds/24/details/4688

2. Jayram GT, Kramolowsky E, Doronina M, et al. Preliminary anti-tumor activity and safety results from ADVANCED-2: a phase 2 open-label study of intravesical TARA-002 in adults with high-grade non-muscle invasive bladder cancer. J Urol. 2025;213(5S):e117. doi:10.1097/01.JU.0001109740.05294.af.40

3. Protara Therapeutics announces positive interim results demonstrating durable responses in the ongoing phase 2 ADVANCED-2 trial of TARA-002 in patients with NMIBC. News release. Protara Therapeutics. April 26, 2025. December 8, 2025. https://ir.protaratx.com/news-releases/news-release-details/protara-therapeutics-announces-positive-interim-results

4. 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 8, 2025. https://ir.protaratx.com/news-releases/news-release-details/protara-therapeutics-announces-updated-interim-data-phase-2