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ADVANCED-002: High CR rates observed with TARA-002 in high-grade NMIBC

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Key Takeaways

  • TARA-002 demonstrated a 100% high-grade complete response in BCG-unresponsive patients at 6 months, with a 76% CR in BCG-naïve patients.
  • The agent acts as a broad-spectrum immune potentiator, potentially offering a more comprehensive immune response than BCG.
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Treatment with TARA-002 was associated with a 100% high-grade CR at any time in BCG-unresponsive participants.

Use of the intravesical agent TARA-002 was found to be well tolerated and also associated with encouraging clinical activity in patients with high-grade non–muscle invasive bladder cancer (NMIBC), according to phase 2 data presented at the 2025 American Urological Association (AUA) Annual Meeting in Las Vegas, Nevada.1,2

Gautam Jayram, MD

Gautam Jayram, MD

In an interview with Urology Times®, study author Gautam Jayram, MD, explained that TARA-002 is unique “because it is its own kind of broad-spectrum immune potentiator. This is probably the most similar to BCG, but it has a broader spectrum approach, where it turns on a bigger cascade of cytokines. Some people talk about immune exhaustion; if you're just stimulating the same cytokines in the same pathway over and over again, that may limit your efficacy. So this is something that may have some interesting mechanistic approaches, where maybe you involve more of the immune system to get a better response.” Jayram is a urologic oncologist and director of the Advanced Therapeutics Center in Nashville, Tennessee.

At AUA, Jayram presented findings from ADVANCED-002 (NCT05951179), described in the poster as “an ongoing, actively enrolling, phase 2, open-label study to evaluate the safety and efficacy of intravesical instillation of TARA‑002 (40 KE) in adults [at least] 18 years with BCG-unresponsive and BCG-naïve (defined as patients who have never been exposed and those who have not received intravesical BCG for at least 24 months) NMIBC with CIS ± Ta/T1 who have active disease.”

The primary end point of the study is high-grade complete response (CR) at any time up to month 6, and the secondary end point is durability of response at month 12. Participants received an induction regimen of 6 weekly doses, reinduction in the event of persistent disease at 3 months, as well as a maintenance regimen of 3 weekly doses at 3, 6, 9, 12, 15 and 18 months. A total of 19 patients with BCG-unresponsive disease and 31 patients with BCG-naïve disease were included in the study.

The investigators reported that treatment with TARA-002 was associated with a 100% high-grade CR at any time in BCG-unresponsive participants.1 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%.2

Jayram made note of the 76% high-grade CR rate in patients with BCG-naïve disease.

“That's really interesting, because usually we see the other way around; we see that the naive group responds better than the unresponsive group. To that point, there could be a priming effect of this treatment, where if you have received previous BCG, you actually may do better with this drug because your immune system has already been primed…I think this is something that's hypothesis generating and something that should be studied because it's really interesting.”

Regarding safety, 32 (74%) participants had any-grade treatment-emergent adverse events (TEAEs), of which 26 (60%) were grade 1, 12 (28%) were grade 2, and 1 (2%) was grade 2. Thirteen (30%) patients had any-grade related TEAEs, of which 12 (28%) were grade 1 and 1 (2%) were grade 2. Six (14%) patients had serious TEAEs, of which 2 (5%) were grade 2 and 6 (14%) were grade 3. No patients had related TEAEs leading to study withdrawal.

“These interim findings support the potential of TARA-002 as an intravesical immunotherapy for high-risk NMIBC,” the investigators wrote in their poster.

“The durable results shared today continue to support our conviction that TARA-002 has the potential to make a meaningful difference in the lives of patients with NMIBC,” said Jesse Shefferman, CEO of Protara Therapeutics in a news release about the data. “Notably, we are particularly pleased with the competitive 12-month CR rates observed in the registrational BCG-Unresponsive cohort as well as the BCG-Naïve cohort. We look forward to continuing to advance this important trial as we work toward our mission of bringing transformative therapies to patients.”2

REFERENCES

1. 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

2. 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. Accessed April 26, 2025. https://ir.protaratx.com/news-releases/news-release-details/protara-therapeutics-announces-positive-interim-results

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