FDA Clears NMIBC Agent TYRA-300 for Phase 2 Trial
TYRA-300 has gained an investigational new drug application from the FDA and will be further studied in the phase 2 SURF302 trial for patients with low-grade, intermediate-risk non–muscle-invasive bladder cancer.
- The FDA cleared the investigational new drug (IND) application for TYRA-300 in low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC).
- TYRA-300 is an investigational, oral, FGFR3-selective inhibitor in development for patients with cancer and skeletal dysplasia, including achondroplasia and hypochondroplasia.
- With this, a phase 2 clinical trial of TYRA-300 in this patient population will begin.
The FDA has cleared the IND application for TYRA-300, an oral FGFR3-selective inhibitor, for use in low-grade, intermediate-risk NMIBC. This regulatory decision paves the way for a phase 2 clinical trial of TYRA-300 in this patient population.1
"For the last 30 years, I have dedicated my career to helping patients with bladder cancer as a urologic oncologist, a principal investigator running clinical trials, and as a drug developer seeking new and more effective therapies for patients with urologic cancers," said Erik Goluboff, MD, MBA, SVP, clinical development of TYRA, in a press release. "I believe that TYRA-300 is the most compelling agent in development for the treatment of [intermediate-risk] NMIBC, with a proven mechanism of action and more attractive tolerability profile than pan-FGFR inhibitors, which made joining TYRA a very exciting opportunity.I look forward to advancing TYRA-300 through the phase 2 SURF302 study and delivering benefit to patients in need."
SURF302 plans to be an open-label, phase 2 trial designed to assess the efficacy and safety of TYRA-300 in patients with FGFR3-altered low-grade, intermediate-risk NMIBC. The study will enroll up to 90 participants across multiple sites, primarily in the US.
Once enrolled, patients will be randomly assigned to receive TYRA-300 at either 50 mg once daily (cohort 1) or 60 mg once daily (cohort 2). Based on initial efficacy and safety results, an additional dosing cohort may be considered.
The primary end point is the complete response (CR) rate at 3 months, and secondary end points include time to recurrence, median duration of response, recurrence-free survival (RFS), progression-free survival (PFS), as well as safety and tolerability.
"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, MD, chief medical officer of TYRA, in a press release."We look forward to leveraging Erik's impressive background to guide our development plans in NMIBC.We expect to initiate patient dosing in the second quarter of this year, with initial three-month CR data to follow."
Bladder cancer stages: © pikovit - stock.adobe.com
About TYRA-300
TYRA-300 is an investigational, oral, FGFR3-selective inhibitor being explored for the treatment of cancer and skeletal dysplasia, including achondroplasia and hypochondroplasia. In oncology, TYRA-300 is being studied in metastatic urothelial cancer (mUC) and intermediate-risk NMIBC.
For mUC, TYRA-300 is currently undergoing evaluation in a multicenter, open-label, phase 1/2 trial, SURF301 (NCT05544552), which aims to determine the recommended phase 2 dose of the agent and evaluate preliminary antitumor activity. Interim proof-of-concept data in mUC from SURF301 was reported in October 2024.2
In the SURF301 study, patients with FGFR3-altered metastatic urothelial cancer treated with TYRA-300 at doses of at least 90 mg per day demonstrated a 54.5% partial response (PR) rate. Notably, 3 of the 6 responses were ongoing at the data cutoff date of August 15, 2024. The overall disease control rate was 100% for those treated at this dose level.
Most patients (n = 10) received 90 mg daily, with a PR rate of 50% observed within this subgroup. Additionally, 1 patient receiving a higher dose of 120 mg daily also demonstrated a PR.
For safety, TYRA-300 was well tolerated with the typical adverse events (AEs) observed with pan-FGFR inhibitors, such as FGFR1 and FGFR2 toxicities, not frequently seen. A total of 10% of patients treated across TYRA-300 dose ranges of 10 mg to 120 mg daily reported serious treatment-related AEs, including 1 case of grade 3 diarrhea at the 90-mg dose and 1 case of grade 3 elevated alanine aminotransferase, leading to treatment discontinuation.
REFERENCES:
Tyra Biosciences receives IND clearance from FDA to proceed with phase 2 study of TYRA-300 in non-muscle invasive bladder cancer (SURF302). News release. Tyra Biosciences. January 10, 2025. Accessed January 10, 2025. https://tinyurl.com/2c68sft3
Tyra Biosciences reports interim clinical proof-of-concept data for TYRA-300, an investigational oral FGFR3-selective inhibitor, in phase 1/2 SURF301 study in patients with metastatic urothelial cancer (mUC). News release. Tyra Biosciences. October 24, 2024. Accessed January 10, 2025. https://tinyurl.com/yc5f5wwn
