“The ADVANCED-2 trial in NMIBC is an exciting opportunity to build on the favorable anti-tumor and safety data of TARA-002 presented earlier this year," says Gautam Jayram, MD.
The first patient has been dosed in the ADVANCED-2 trial1 (NCT05951179) exploring the cell-based therapy TARA-002 in patients with non-muscle invasive bladder cancer (NMIBC) with high-grade carcinoma in situ (CIS), Protara Therapeutics, the developer of the therapy, announced in a news release.2
The ADVANCED-2 trial is an open-label expansion study set to evaluate the safety and anti-tumor activity of intravesical instillation of TARA-002 in 102 patients with CIS who are BCG-naïve (n = 27) or BCG-unresponsive (n = 75). All patients included in the study will undergo an induction course of 6 weekly instillations of TARA-002 at the recommended phase 2 dose with or without a reinduction course. Patients in the BCG-unresponsive cohort will then receive a maintenance course of 3 weekly instillations every 3 months.
The initiation of the phase 1b/2 trial comes after preliminary results from the ADVANCED-1 trial3 (NCT05085977), which showed promising safety and efficacy of the therapy in patients with high-grade NMIBC.4 Results from the study were presented at the American Urological Association 2023 Annual Meeting in Chicago, Illinois.
“The ADVANCED-2 trial in NMIBC is an exciting opportunity to build on the favorable anti-tumor and safety data of TARA-002 presented earlier this year. There is significant need for new intravesical approaches for NMIBC, which can recur and progress to invasive disease with current treatments. This trial looks at the potential clinical benefit of TARA-002 as a possible new therapy for NMIBC, across both BCG-naïve and BCG-unresponsive patient populations,” said study investigator Gautam Jayram, MD, in the news release.2 Jayram is director of the advanced therapeutics center at Urology Associates, P.C. and an associate professor of urology at Vanderbilt University in Nashville, Tennessee.
The ADVANCED-1 trial is an open-label phase 1a dose-escalation study exploring the safety and toxicity of TARA-002 in patients with high-grade NMIBC. In total, 9 patients were enrolled in the study, of which 3 had CIS. All patients with CIS demonstrated anti-tumor activity with the treatment, and 1 heavily pre-treated BCG-unresponsive patient achieved a completed response.
Additional preliminary results showed that the therapy was well-tolerated, with no dose-limiting toxicities observed. The majority of adverse events reported were grade 1 or 2 across all dose levels. Treatment-related adverse events were consistent with typical responses to bacterial immunopotentiation.
Further, the investigators identified the recommended phase 2 dose level as 40KE (Klinische Einheit), which will be used in the ADVANCED-2 study.
In addition to ADVANCED-2, TARA-002 is also being evaluated in the ongoing phase 1b ADVANCED-1EXP trial.
“Following positive preliminary results from the ADVANCED-1 trial, we are pleased to have dosed the first patient in the ADVANCED-2 trial. We believe TARA-002 has the potential to play a meaningful role in the NMIBC treatment landscape and look forward to progressing the trial in parallel with our ongoing ADVANCED-1EXP study,” Jathin Bandari, MD, the Chief Medical Officer of Protara Therapeutics, said in the news release.2
The ADVANCED-1EXP trial is an open-label study that enrolled 12 patients with CIS who are BCG-naïve, BCG-unresponsive, or who were inadequately treated with BCG. Results from the ADVANCED-1EXP trial are expected in the first half of 2024.
1. National Institutes of Health US National Library of Medicine ClinicalTrials.gov. Dose expansion, safety and efficacy study of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer (ADVANCED-2). Last updated July 18, 2023. Accessed September 20, 2023. https://clinicaltrials.gov/study/NCT05951179
2. Protara Therapeutics announces dosing of first patient in phase 1b/2 ADVANCED-2 trial of TARA-002 in NMIBC patients with high-grade carcinoma in situ. News release. Protara Therapeutics. Published online and accessed September 20, 2023. https://www.globenewswire.com/news-release/2023/09/20/2746463/0/en/Protara-Therapeutics-Announces-Dosing-of-First-Patient-in-Phase-1b-2-ADVANCED-2-Trial-of-TARA-002-in-NMIBC-Patients-with-High-Grade-Carcinoma-in-Situ.html
3. National Institutes of Health US National Library of Medicine ClinicalTrials.gov. Safety and toxicity study of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer (Phase 1a) (ADVANCED-1). Last updated July 11, 2023. Accessed September 20, 2023. https://clinicaltrials.gov/study/NCT05085977
4. Protara Therapeutics announces positive preliminary data from ADVANCED-1 phase 1a dose escalation trial of TARA-002 in NMIBC supporting advancement into phase 2 clinical development. News release. Protara Therapeutics. April 28, 2023. Accessed September 20, 2023. https://www.biospace.com/article/releases/protara-therapeutics-announces-positive-preliminary-data-from-advanced-1-phase-1a-dose-escalation-trial-of-tara-002-in-nmibc-supporting-advancement-into-phase-2-clinical-development/