FDA greenlights phase 2 SURF302 trial of TYRA-300 in NMIBC

The FDA has granted clearance to an investigational new drug (IND) application to initiate a phase 2 trial of TYRA-300 in patients with FGFR3-altered low-grade, intermediate-risk non-muscle invasive bladder cancer (NMIBC), Tyra Biosciences announced in a news release.¹

The open-label study plans to enroll up to 90 patients with NMIBC.

The study, titled SURF302, will evaluate the safety and efficacy of the FGFR3-selective inhibitor in this patient population. The program will be led by Erik Goluboff, MD, MBA, SVP, Clinical Development of TYRA.

"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, in the news release.¹ "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 [complete response] data to follow."

In total, the open-label study plans to enroll up to 90 patients across clinical trial sites in the US. Those included in the trial will be randomly assigned to receive 50 mg TYRA-300 once daily (cohort 1) or to 60 mg TYRA-300 once daily (cohort 2). An additional dosing cohort may be added depending on an initial review of safety and efficacy outcomes.

The primary end point for the trial is the complete response rate at 3 months. Secondary end points will include time to recurrence, median duration of response (DOR), recurrence-free survival, progression-free survival (PFS), safety, and tolerability.

Additional data on TYRA-300

In addition to the SURF302 trial, TYRA-300 is also under investigation in metastatic urothelial carcinoma in the phase 1/2 SURF301 trial (NCT05544552) and in pediatric achondroplasia in the BEACH301 trial.

Interim data from the SURF301 trial were reported in October 2024.^2,3 Overall, the agent demonstrated initial efficacy while maintaining a favorable tolerability profile in patients with metastatic urothelial carcinoma.

The preliminary analysis included a total of 41 patients at the time of data cutoff. For the trial, TYRA-300 was evaluated across 6 dose levels, ranging from 10 mg to 120 mg once daily.

In patients with FGFR3-altered mUC, anti-tumor activity was observed across all patients who were treated at the dose levels of 90 mg and higher. In these cohorts, 54.5% of patients (6 of 11) achieved a partial response. This consisted of 5 patients (50%) in the 90 mg cohort and 1 patient (100%) in the 120 mg cohort. Three partial responses were still ongoing at the time of data report.

Additionally, the disease control rate, consisting of partial response plus stable disease, was 100% among patients with mUC who received TYRA-300 at 90 mg or higher.

According to the authors, the therapy was also generally well-tolerated. There were 4 (10%) serious adverse events (AEs) related to TYRA-300 across all dose levels (10 mg to 120 mg). Of these, 1 was a grade 3 dose-limiting toxicity in the 90 mg cohort, and 2 were grade 3 treatment-related AEs (TRAEs) of increased ALT in the 90 mg cohort, 1 of which led to the discontinuation of treatment.

Overall, AEs of any grade occurred in 78% of patients (n = 32), and AEs of grade 3 or higher occurred in 20% of patients (n = 8). No grade 4 or higher TRAEs were reported. Additionally, no dose-limiting toxicities were observed among patients in the highest dose cohort of 120 mg at the time of data cutoff.

The ongoing SURF301 trial is enrolling participants with mUC and other solid tumors who harbor FGFR3 gene alterations. At the time of data cutoff, 61% of patients (n = 25) in the trial had mUC. Among all patients with FGFR3-altered mUC, 76% had received at least 3 prior lines of therapy. The median age among all participants was 66 years.

Enrollment for the trial is taking place at 21 clinical trial sites across the United States, Europe, and Australia.⁴ For phase 1 of the study, patients will receive TYRA-300 at dose levels ranging from 10 mg to 120 mg once or twice daily. In phase 2, patients will receive TYRA-300 at the recommended phase 2 dose level determined in the first phase.

The primary end points for phase 1 include the incidence of dose-limiting toxicities and adverse events, as well as other safety parameters. Secondary end points include pharmacokinetic parameters, overall response rate, DOR, duration of complete response, time to response, and PFS.

Phase 1 of the study remains ongoing to determine the maximum tolerated dose.

References

1. 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. Published online and accessed January 10, 2025. https://ir.tyra.bio/news-releases/news-release-details/tyra-biosciences-receives-ind-clearance-fda-proceed-phase-2-0

2. Tran B, Zhang A, Hansen A, et al. Preliminary safety and anti-tumor activity of TYRA-300, a highly selective FGFR3 inhibitor, in participants with advanced solid tumors with activating FGFR3 mutations/fusions (SURF301). Presented at: 36th EORTC-NCI-AACR (ENA) Symposium on Molecular Targets and Cancer Therapeutics. October 23-25, 2024. Barcelona, Spain. Abstract 500LBA

3. 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, Inc. October 24, 2024. Accessed January 10, 2025. https://ir.tyra.bio/news-releases/news-release-details/tyra-biosciences-reports-interim-clinical-proof-concept-data

4. Safety and preliminary anti-tumor activity of TYRA-300 in advanced urothelial carcinoma and other solid tumors with FGFR3 gene alterations (SURF301). ClinicalTrials.gov. Updated October 3, 2024. Accessed January 10, 2025. https://clinicaltrials.gov/study/NCT05544552