TARA-002 Intravesical Therapy Generates High CR Rate in BCG-Naive NMIBC With CIS

Intravesical TARA-002 produced a complete response rate (CR) of 72.4% at any time in evaluable patients with BCG-naive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), according to updated interim data from the ongoing, open-label, phase 2 ADVANCED-2 trial (NCT05951179).1,2

As of the November 7, 2025, data cutoff, 29 of the 31 patients who received at least 1 dose of TARA-002 had completed at least 1 response assessment and were efficacy evaluable. The CR rates at 6 and 12 months were 69.2% (n = 18/26) and 50% (n = 7/14), respectively.

Notably, 88% of the 16 initial responders maintained their response through 6 months; 100% of responders (n = 3/3) maintained a response through 12 months.1 Additionally, re-induction therapy led to high conversion rates and durable responses in the majority of initial nonresponders, with 80% of re-induced patients (n = 5) converting to a CR at 6 months. All 4 of those responders maintained their CR at 12 months.

Regarding safety, the agent displayed a favorable tolerability profile in this patient population (n = 31), according to investigators.1,2 Treatment-related adverse effects (TRAEs) were primarily grade 1, occurring in 26% of patients, and no grade 3 or greater TRAEs were reported. Moreover, no patients discontinued treatment due to TRAEs, and no serious TRAEs were observed. The most common any-grade TRAEs were dysuria (13%), fatigue (13%), and hematuria (6%).

These results were reviewed in a live webcast hosted by Protera Therapeutics following their presentation in a poster session at the 26th Annual Meeting of the Society of Urologic Oncology.

“These encouraging results demonstrate meaningful and durable activity in [patients with] BCG-naive NMIBC,” Mark Tyson, MD, MPH, an ADVANCED-2 study investigator, as well as the vice chair for Research and a professor in the Department of Urology with the Mayo Clinic in Phoenix, Arizona, stated 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-naive setting.”

What is the design of ADVANCED-02?

This phase 2, open-label trial comprises 2 cohorts: patients with BCG-naive NMIBC with CIS (cohort A), and those with BCG-unresponsive NMIBC with CIS (cohort B; n = 100).2 Upon enrollment, patients are receiving an induction course comprised of 6 weekly intravesical instillations of TARA-002. Eligible patients with residual CIS and/or recurrent high-grade Ta disease will undergo reinduction of this regimen. All patients will then receive a maintenance course of 3 weekly instillations every 3 months through month 18, and then again at month 24.

The study’s primary end point is CR rate at any time during the first 6 months of treatment. Twelve-month duration of response is a key secondary end point.

What is the registrational path forward for TARA-002?

The FDA has provided written feedback supporting a registrational, controlled trial in patients with BCG-naive NMIBC, defined as those who have never been exposed to, or have not received, BCG within the last 24 months; those who are ineligible to receive BCG; and those who are contraindicated for, cannot tolerate, do not have access to, or refuse BCG.1 The FDA has also agreed that BCG is not required as a comparator, noting that intravesical chemotherapy is an acceptable comparator in the BCG-naive cohort.

Of note, Protera Therapeutics is working with the FDA to determine how patients with BCG-exposed NMIBC may be included in ongoing or future clinical trials evaluating TARA-002.

TARA-002 was previously granted rare pediatric disease designation by the FDA for the treatment of patients with NMIBC and lymphatic malformations.

“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-naive patients,” Jesse Shefferman, chief executive officer of Protara Therapeutics, stated in a news release. “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

1. Protara Therapeutics announces updated interim data from phase 2 ADVANCED-2 trial of TARA-002 in BCG-baïve NMIBC patients. News release. Protara Therapeutics. December 3, 2025. Accessed December 3, 2025. https://ir.protaratx.com/news-releases/news-release-details/protara-therapeutics-announces-updated-interim-data-phase-2
2. Protara Therapeutics SUO update call. Webcast. Protara Therapeutics. December 3, 2025. Accessed December 3, 2025. https://protara-therapeutics-suo-update-call.open-exchange.net/webcast