Cell therapy TARA-002 shows initial promise in NMIBC

The cell therapy TARA-002 demonstrated a favorable safety profile and preliminary anti-tumor activity in patients with high-risk non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), according to 3-month data from the phase 1a/b ADVANCED-1 and phase 2 ADVANCED-2 clinical trials published in a news release by Protara Therapeutics, the developer of the therapy.¹

Data from all 3 trials showed a 3-month complete response rate of 38% among the 16 evaluable patients prior to reinduction.

“These promising 3-month results support the continued development of TARA-002 for patients with NMIBC for whom there are currently limited treatment options,” said study investigator Timothy D. Lyon, MD, an associate professor of urology and the Urology Residency Program Director at the Mayo Clinic in Florida, in the news release.¹ “Given our understanding that up to half of patients treated with intravesical immune therapies that do not initially respond can be salvaged with repeat induction, there is reason to believe that the promising 3-month response rates shared today could be further improved through reinduction with TARA-002. This encouraging anti-tumor activity coupled with a favorable safety profile and mode of administration that is both convenient and familiar to urologists indicates that, if confirmed in future studies, TARA-002 could potentially play a meaningful role in NMIBC treatment in the future.”

Data from the study were pooled from the phase 1a ADVANCED-1 (NCT05085977), phase 1b-expansion ADVANCED-1 (NCT05085990), and phase 2 ADVANCED-2 (NCT05951179) trials of TARA-002. The ADVANCED-1 phase 1a and 1b expansion trials included patients with BCG-unresponsive, BCG-naïve, and BCG-experienced high-risk NMIBC with CIS and CIS +Ta/T1. The ADVANCED-2 clinical trial included patients with BCG-unresponsive and BCG-naïve high-risk NMIBC with CIS (± Ta/T1).

Overall, data from all 3 trials showed a 3-month complete response (CR) rate of 38% among the 16 evaluable patients prior to reinduction. CIS-only patients demonstrated a CR of 63% (5/8), and patients with CIS with or without Ta/T1 demonstrated a CR of 13% (1/8). Patients with BCG-unresponsive or BCG-experienced NMIBC achieved a CR rate of 43%, and patients who were BCG-naïve achieved a CR rate of 33%.

Regarding safety, the majority of adverse events (AEs) were grade 1 and 2 across all dose levels. Treatment-emergent AEs (TEAEs) were consistent with previously reported data on responses to bacterial immunopotentiation. Reported TEAEs included fatigue, headache, fever, and chills. Urinary urgency, urinary frequency, urinary tract pain/burning, incomplete emptying, and bladder spasm were the most common urinary symptoms reported. No grade 3 TEAEs were observed.

Overall, the phase 1a study included 18 patients and the phase 1b expansion study included up to 12 patients with BCG-unresponsive, BCG-naïve, or BCG-experienced NMIBC with CIS and CIS +Ta/T1. Patients were treated with TARA-002 at the dose level of 40KE.The primary end point for the phase 1 study was safety and complete response rate at 3-month follow-up.

The phase 2 trial plans to enroll at least 102 patients with BCG-unresponsive (n = 75-100) or BCG-naïve (n = 27) NMIBC with CIS (± Ta/T1).Patients in the study received an induction course of 6 weekly intravesical instillations of TARA-002 followed by reinduction—if eligible—or maintenance therapy for up to 24 months.

The investigators plan to add 2 exploratory cohorts of patients to the ADVANCED-2 trial to assess TARA-002 at the higher dose level of 80KE (cohort C) as well as to explore the use of systemic priming prior to the initiation of intravesical administration (cohort D). Results from 6-month follow-up of the ADVANCED-2 trial are expected in the second half of 2024, which will include preliminary results from a pre-planned risk-benefit analysis of 10 patients.

Protara also plans to initiate a proof-of-concept study to assess the synergistic effects of TARA-002 in combination with pembrolizumab (Keytruda) in patients with NMIBC with CIS.

Reference

1. Protara Therapeutics announces positive three-month data from TARA-002 clinical program in NMIBC. News release. Protara Therapeutics. April 5, 2024. Accessed April 9, 2024. https://ir.protaratx.com/news-releases/news-release-details/protara-therapeutics-announces-positive-three-month-data-tara