(UroToday.com) The 2024 Society of Urologic Oncology (SUO) annual meeting held in Dallas, between December 3 and December 6, 2024, was host to the Abstract/Posters Session. Dr. Brian Mazzarella discussed the results from ADVANCED-2: a Phase 2 open-label study to evaluate the safety and anti-tumor activity of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer.
Considering the ongoing Bacillus Calmette-Guérin (BCG) shortage and the limited availability of effective alternative therapies, there remains a significant unmet need for treatment options for patients with non-muscle invasive bladder cancer (NMIBC) requiring intravesical BCG.
TARA-002 is a promising broad-spectrum immune potentiator that induces a TH1 pro-inflammatory cytokine response. It is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) strain treated with benzylpenicillin. TARA-002 is currently being developed for the treatment of high-grade NMIBC.
ADVANCED-2 (NCT05951179) is an ongoing, actively enrolling Phase 2 open-label study designed to evaluate the safety and efficacy of intravesical instillation of TARA-002 in adults aged 18 and older with BCG-unresponsive and BCG-naïve CIS or Ta/T1 with active disease. The treatment schedule includes a 6-weekly instillation induction and a 3-weekly instillation maintenance up to 18 months.
The primary endpoint of the study is the high-grade complete response (CR) at any time up to month 6 of treatment, and the secondary endpoint is the durability of response at 12 months. The trial schema is illustrated below:
To date, 24 patients have been enrolled in the ADVANCED-2 study. All participants were white, with the majority being non-Hispanic (96%) and male (79%). The median age of the study cohort was 71 years. The Eastern Cooperative Oncology Group (ECOG) score was 0 for 75% of the subjects, indicating they were fully active and able to carry on all pre-disease activities without restriction. Most patients had a baseline diagnosis of CIS only (58%), while 25% had CIS + Ta disease, and 17% had CIS + T1 disease.
Regarding the primary objective, the rates of high-grade complete response (CR) at any time were 70% overall, with 80% for BCG-unresponsive subjects and 67% for BCG-naive subjects. At Month 6, the rates of high-grade CR were 72% overall, 100% for BCG-unresponsive subjects, and 64% for BCG-naive subjects, as illustrated below.
The secondary objective was to assess the duration of response to TARA-002. A total of (9 out of 9 (!00%) of subjects who were complete responders at Month 3, and continued the study, maintained response through Month 6 as can be appreciated in the swimmer’s plot below. Notably, of the 5 subjects who did not achieve initial CR and received re-induction, the CR rate at Month 6 was 80%.
Lastly, the investigators evaluated the safety profile of TARA-002 intravesical therapy. The majority of treatment-emergent adverse events (TEAEs) were mild, with 46% being Grade 1 and 29% being Grade 2, and all were transient. Importantly, no subjects experienced drug-related serious adverse events (SAEs) or TEAEs leading to withdrawal or death.
Notably, the most common treatment-emergent adverse events (TEAEs) observed were bladder spasms, burning sensation, and urinary tract infections (UTIs). These side effects are consistent with the known safety profile of immune-potentiating drugs, which often include flu-like symptoms.
Dr Mazarella concluded his poster presentation with the following takeaways:
- TARA-002 appears to be well-tolerated with encouraging efficacy, showing a 72% high-grade complete response (HG-CR) at 6 months and durability of response in subjects with high-risk NMIBC with CIS.
- Further studies are planned to explore the potential of TARA-002 in both BCG-naive and BCG-unresponsive populations.
Presented by: Brian Mazzarella, MD, FACS, Affiliate Faculty at Dell Medical School at the University of Texas at Austin, TX.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) Luis Carlos Sarmiento Angulo Foundation via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2024 Society of Urologic Oncology (SUO) annual meeting held in Dallas, between the 3rd and 6th of December, 2024.