TYRA-300 Phase 2 Trial for Non-Muscle Invasive Bladder Cancer Gets FDA Green Light
Key Insights
The FDA has cleared Tyra Biosciences' IND application for TYRA-300, allowing a Phase 2 trial in low-grade, intermediate-risk non-muscle invasive bladder cancer (search) (NMIBC).
The SURF302 trial will evaluate the safety and efficacy of TYRA-300, an oral FGFR3 (search)-selective inhibitor, in patients with FGFR3-altered NMIBC.
The open-label study will enroll up to 90 patients, with the primary endpoint being the complete response rate at 3 months, with patient dosing expected in Q2 2025.
Tyra Biosciences has received FDA clearance for its Investigational New Drug (IND) application for TYRA-300, paving the way for a Phase 2 clinical trial (SURF302) in patients with FGFR3 (search)-altered low-grade, intermediate-risk non-muscle invasive bladder cancer (search) (NMIBC). This open-label study will evaluate the safety and efficacy of TYRA-300, a selective FGFR3 inhibitor, in this specific patient population, addressing a significant unmet need for better-tolerated therapeutic options. The trial is set to begin patient dosing in the second quarter of 2025, with initial data expected shortly thereafter.
The SURF302 trial plans to enroll up to 90 patients across multiple clinical trial sites in the US. Participants will be randomized to receive either 50 mg or 60 mg of TYRA-300 once daily. An additional dosing cohort may be added based on initial safety and efficacy reviews. The primary endpoint of the trial is the complete response rate at 3 months, with secondary endpoints including time to recurrence, median duration of response, recurrence-free survival, progression-free survival, safety, and tolerability.
Addressing Unmet Needs in NMIBC
In the United States, over 730,000 individuals are living with bladder cancer (search), with a significant portion experiencing intermediate-risk NMIBC and recurring episodes. Current treatments, involving surgical resection and intravesical chemotherapy, can negatively impact patients' quality of life, highlighting the need for more effective and tolerable therapies. TYRA-300, as an orally administered investigational agent, represents a potential advancement in the treatment landscape.
TYRA-300: A Selective FGFR3 Inhibitor
TYRA-300 is a selective FGFR3 (search) inhibitor designed to avoid the toxicities associated with inhibiting FGFR1, FGFR2, and FGFR4, while remaining effective against FGFR3 gatekeeper mutations. FGFR3 is frequently altered in NMIBC, present in 60-80% of intermediate-risk cases. TYRA-300 is also being investigated in the Phase 1/2 SURF301 trial for metastatic urothelial carcinoma (search) and the BEACH301 trial for pediatric achondroplasia (search).
Promising Early Data in Metastatic Urothelial Carcinoma
Interim data from the SURF301 trial in metastatic urothelial carcinoma (search), reported in October 2024, demonstrated initial efficacy and a favorable tolerability profile for TYRA-300. The analysis included 41 patients, with TYRA-300 evaluated at doses ranging from 10 mg to 120 mg once daily. In patients with FGFR3 (search)-altered mUC treated with 90 mg or higher, 54.5% (6 of 11) achieved a partial response. The disease control rate in this cohort was 100%.
The therapy was generally well-tolerated, with 10% of patients experiencing serious adverse events related to TYRA-300 across all dose levels. No grade 4 or higher treatment-related adverse events were reported, and no dose-limiting toxicities were observed in the highest dose cohort of 120 mg.
Leadership Perspective
"Receiving FDA IND clearance is an important milestone in the advancement of TYRA-300 and for patients with NMIBC who urgently need better tolerated therapeutic options," said Doug Warner, Chief Medical Officer of TYRA. Erik Goluboff, MD, MBA, SVP, Clinical Development of TYRA, added, "I believe that TYRA-300 is the most compelling agent in development for the treatment of IR NMIBC, with a proven mechanism of action and more attractive tolerability profile than pan-FGFR inhibitors."