Protara Reports Positive Phase 2 ADVANCED-2 Trial Results for TARA-002 in NMIBC Patients

Protara Therapeutics, Inc., a clinical-stage company focused on developing transformative therapies for cancer and rare diseases, has announced significant findings from its ongoing Phase 2 ADVANCED-2 trial. This study is evaluating the effectiveness of TARA-002, an investigational cell-based therapy, in patients with high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) who are either unresponsive or new to Bacillus Calmette-Guérin (BCG) treatment. The trial’s outcomes highlight a promising treatment avenue for these patients.

The data revealed that TARA-002 achieved a 72% complete response (CR) rate at the six-month mark and a 70% CR rate at any point during the study across various BCG exposures. Notably, 100% of patients who responded positively at three months maintained their response through six months. Furthermore, additional observations indicated that two out of three patients continued to show a complete response at nine months. These findings were presented at the 25th Annual Meeting of the Society of Urologic Oncology (SUO) in Dallas, Texas.

The study included 20 patients evaluated at three months, 18 at six months, and three at nine months, with data collected up until November 19, 2024. In the BCG-Unresponsive cohort, the CR rate was 100% at six months and 80% at any time. For BCG-Naïve patients, the CR rate was 64% at six months and 67% at any time. TARA-002 also demonstrated a favorable safety profile, with no Grade 2 or higher treatment-related adverse events, and no patients discontinued the treatment due to adverse events.

Brian Mazzarella, MD, Vice President of Research for Urology America and investigator in the ADVANCED-2 study, expressed enthusiasm over the results, stating that TARA-002 shows significant activity in treating a challenging patient group. He highlighted the therapy’s ease of use and minimal procedural burden for physicians, making it an appealing treatment option for NMIBC patients.

Jesse Shefferman, CEO of Protara Therapeutics, echoed these sentiments, emphasizing the potential of TARA-002 to impact NMIBC treatment positively. Shefferman noted that the encouraging data, combined with international site expansion, would likely expedite patient enrollment. The company plans to report additional data from 12-month evaluable patients by mid-2025.

The majority of adverse events reported were Grade 1 and temporary, aligning with typical immune responses to bacterial immunopotentiation, such as flu-like symptoms and urinary tract irritation. These symptoms were generally mild and resolved shortly after treatment.

The Phase 2 ADVANCED-2 trial is evaluating TARA-002 in NMIBC patients with carcinoma in situ (CIS), including those who are BCG-Unresponsive (approximately 100 patients) and BCG-Naïve (27 patients). The trial’s design aligns with the FDA’s 2024 guidelines for developing treatments for BCG-Unresponsive NMIBC.

TARA-002 is derived from the same master cell bank as OK-432, a broad immunopotentiator marketed in Japan as Picibanil® and approved in Taiwan. Protara Therapeutics has successfully demonstrated manufacturing comparability between TARA-002 and OK-432.

When administered, TARA-002 is believed to activate innate and adaptive immune cells within the cyst or tumor, leading to a pro-inflammatory response and cytokine release. This immune reaction is thought to directly kill tumor cells and enhance the body’s antitumor response.

Bladder cancer is prevalent in the United States, with NMIBC constituting about 80% of diagnoses. Annually, around 65,000 new cases of NMIBC are identified in the U.S. This type of cancer is located in the bladder lining and has not invaded the bladder muscle.

Protara Therapeutics is focused on advancing therapies for cancer and rare diseases. Their portfolio includes TARA-002, which is under investigation for treating NMIBC and lymphatic malformations (LMs). Additionally, the company is developing IV Choline Chloride for patients requiring parenteral nutrition who cannot meet their choline needs through oral or enteral intake.