The ADVANCED-2 trial plans to build onto the early antitumor and safety data seen with TARA-002 that were presented this year for patients with non-muscle invasive bladder cancer.
Trial Name: A Phase 1b/2, Dose Expansion, Open-label Study to Evaluate Safety and Anti-tumor Activity, of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer
ClinicalTrials.gov Identifier: NCT05951179
Sponsor: Protara Therapeutics
Recruitment Contact: Chief Scientific Operations Officer, 16468440337, clinicaltrials@protaratx.com
Completion Date: August 2026
The first patient with non-muscle invasive bladder cancer (NMIBC) with Bacillus Calmette-Guérin (BCG)-naïve and BCG-unresponsive carcinoma in situ (CIS) has been dosed with TARA-002 in the phase 1b/2 ADVANCED-2 trial (NCT05951179).1
This trial follows the announcement of positive results from the ADVANCED-1 trial (NCT05085990) which also evaluated TARA-002 in this patient population.
The most recent data show that in the dose-escalation portion of the study, treatment with TARA-002 led to antitumor activity, including tumor regression, in all 3 of the evaluable patients with CIS. This patient population included 1 patient with heavily pre-treated BCG-unresponsive NMIBC who achieved a complete response (CR). Additionally, was treatment with TARA-002 was generally well-tolerated.
“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,” said Tom Jayram, MD, director, Advanced Therapeutics Center, Urology Associates, P.C., TN, and study investigator for the ADVANCED-2 trial, in a press release. “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.”
TARA-002 is an investigational cell therapy being developed to treat NMIBC and lymphatic malformations. Previously, the agent was granted a rare pediatric disease designation by the FDA. The same master cell bank of of genetically distinct group A Streptococcus pyogenes were used to develop both TARA-002 and OK-432, and manufacturing comparability has been shown between the 2 products.
When administered, TARA-002 is expected to activate and produce a strong immune cascade in innate and adaptive immune cells within the cyst or tumor. Additionally, Neutrophils, monocytes and lymphocytes infiltrate the abnormal cells and various cytokines, including interleukins (ILs) like IL-2, IL-6, IL-8, IL-10, IL-12, interferon-gamma, and tumor necrosis factor-alpha are secreted by immune cells to induce a strong local inflammatory reaction and destroy the abnormal cells.
In the phase 1b/2 ADVANCED-2 study, up to 102 patients with NMIBC who are BCG-naïve (n = 27) and BCG-unresponsive (n = 75) with CIS are being evaluated and treated with intravesical TARA-002. The open-label will administer patients an induction with or without a reinduction course of 6 intravesical instillations of TARA-002 a week, followed by a maintenance course of 3 weekly installations every 3 months in the BCG-unresponsive cohort.
Patients 18 years and older with central histologic confirmation of high-grade non-muscle invasive CIS with active disease who are unable to obtain intravesical BCG, have not received intravesical BCG for 24 months prior to CIS diagnosis, or have persistent or recurrent CIS within 12 months of completion of adequate BCG are eligible for enrollment in the study.2
For cohort A, primary end points being assessed include incidence of high-grade CR, and secondary end points include incidence and severity of adverse events (AEs), treatment-emergent AEs (TEAEs), serious AEs (SAEs), and treatment-emergent serious AEs (TESAEs), and quality of Life based on the European Organization for Research and Treatment of Cancer questionnaire. In cohort B, the primary end point being evaluated is incidence of CR with secondary end points of duration of high-grade CR, complete response rate, progression-free survival (PFS), disease-specific PFS, overall survival, time to cystectomy, time to recurrence delayed cystectomy, time to progression after treatment, time to disease worsening after treatment, incidence and severity of AEs, TEAEs, SAEs, and TESAEs, change from baseline in inflammatory urine cytokines levels, and quality of life.
Further, dosing is progressing in the ongoing ADVANCED-EXP trial which began earlier this year and is evaluating 12 CIS patients with TARA-002. The phase 1b, open-label, expansion study will include patients with NMIBC who are BCG-naïve, BCG-unresponsive, or BCG-inadequately treated. Preliminary results from this study are expected to be released in the first half of 2024.1
“Following positive preliminary results from the ADVANCED-1 trial, we are pleased to have dosed the first patient in the ADVANCED-2 trial,” said Jathin Bandari, MD, chief medical officer of Protara Therapeutics, in a press release. “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.”
