ADVANCED-2 data demonstrate safety, efficacy of TARA-002 in NMIBC

Researchers reported positive safety and efficacy data for TARA-002, an investigational treatment for patients with high-grade non–muscle invasive bladder cancer (NMIBC), at the Society of Urologic Oncology 25th Annual Meeting in Dallas, Texas.¹

“TARA-002 is a broad spectrum immune potentiator that elicits a TH1 pro-inflammatory cytokine response. [It] is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin,” the authors wrote in their poster.

The phase 2 ADVANCED-2 trial (NCT05951179) is an ongoing open-label study that is actively enrolling. It is evaluating the safety and efficacy of intravesical instillation of TARA-002 (40 KE) in adults 18 years of age and older who have BCG-unresponsive or BCG-naïve carcinoma in situ (CIS) NMIBC (+/- Ta/T1 with active disease. The primary end point is high-grade complete response (CR) at any time up to month 6. “[The] key secondary end point is durability of response at month 12,” wrote the authors.

“The dataset includes 20 patients who were evaluable at 3 months, 18 patients who were evaluable at 6 months, and 3 patients who were evaluable at 9 months with a data cut-off of November 19, 2024,” according to a news release about the study.²

All patients were Caucasian, with the majority being non-Hispanic and male. Median age was 71 years. ECOG score was 0 for 18 of 24 (75%) patients. Fourteen (58%) patients had a baseline diagnosis of CIS only, 6 (25%) patients had CIS + Ta disease, and 4 (17%) patients had CIS + T1 disease.

The investigators reported an overall high-grade CR rate at any time of 70% (14 of 20). In addition, high-grade CR rate for patients who were BCG-unresponsive was 80% (4 of 5), and in patients who were BCG naïve, the high-grade CR rate was 67% (10 of 15).

At month 6, the overall high-grade CR rate was 72% (13 of 18). The rate was 100% (4 of 4) patients who were BCG-unresponsive and 64% (9 of 14) for those with BCG-naïve disease. In addition, 100% (9 of 9) of patients who had a CR at month 3 and who continued the study maintained response through month 6.

Five subjects did not achieve an initial CR and received re-induction. In this group, “the CR rate at month 6 was 80% (4 of 5),” the authors wrote.

Regarding safety, the majority of treatment-emergent adverse events (TEAEs) were grade 1 and transient. Sixteen (67%) patients experienced a TEAE of any grade, 6 (25%) had a related TEAE of any grade, 3 (13%) had a serious TEAE of any grade, and 0 patients had a TEAE leading to study drug withdrawal or death.

“AEs were consistent with the known safety profile of an immune-potentiating drug, such as flu-like symptoms,” the authors wrote.

Brian Mazzarella, MD

“These impressive TARA-002 results demonstrate meaningful activity in a difficult to treat patient population,” said Brian Mazzarella, MD, vice president of research for Urology America and ADVANCED-2 study investigator, in the news release.² “The activity of TARA-002 across BCG exposures, coupled with its ease of use and low procedural burden for physicians, make it an exciting potential treatment option for NMIBC patients.”

REFERENCES

1. Mazzarella B, Jayram G, Shore S, et al. ADVANCED-2: phase 2 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. Presented at: Society of Urologic Oncology 25th Annual Meeting. December 4-6, 2024. Dallas, Texas. Abstract 119. Accessed December 5, 2024. https://suo-abstracts.secure-platform.com/a/gallery/rounds/21/details/3637

2. Protara announces positive results from the ongoing phase 2 ADVANCED-2 trial of TARA-002 in patients with NMIBC. News release. Protara Therapeutics, Inc. December 5, 2024. Accessed December 5, 2024. https://www.globenewswire.com/news-release/2024/12/05/2992222/0/en/Protara-Announces-Positive-Results-from-the-Ongoing-Phase-2-ADVANCED-2-Trial-of-TARA-002-in-Patients-with-NMIBC.html