Phase 2 trial of TYRA-300 launches in LG-IR-NMIBC

The first patient has been dosed in the phase 2 SURF302 trial (NCT06995677), assessing the safety and efficacy of TYRA-300 in patients with FGFR3-altered low-grade, intermediate-risk non–muscle invasive bladder cancer (LG-IR-NMIBC), Tyra Biosciences announced in a news release.¹

According to the company, TYRA-300 is “a potential first-in-class, investigational, oral, FGFR3-selective inhibitor designed to minimize the toxicities associated with inhibition of FGFR1, FGFR2 and FGFR4, while being agnostic for FGFR3 gatekeeper mutations.”

Tom Jayram, MD

"I am excited that the phase 2 trial evaluating oral TYRA-300 in IR NMIBC is now underway," said Tom Jayram, MD, director of the Advanced Therapeutics Center at Urology Associates in Nashville, Tennessee, in the news release.¹ "IR NMIBC is a challenging disease for urologists and patients alike, with the potential for recurrence, progression, and the morbidity of multiple procedures for disease surveillance. Selective FGFR inhibitors are an exciting new option in this disease space that can allow a personalized approach to bladder cancer. TYRA-300 is an investigational, daily oral tablet that has shown encouraging preliminary safety and efficacy in an early phase trial and has the potential to be a paradigm shift in how urologists can treat bladder cancer."

In total, the open-label, phase 2 SURF302 trial plans to enroll up to 90 adult patients across clinical trial sites primarily in the US.² To be eligible for enrollment, patients must have a documented activating FGFR3 mutation or fusion; an ECOG score of 0 to 1; and adequate bone marrow, liver, and renal function. Additionally, patients cannot have received BCG within 1 year prior to the date of consent nor intravesical chemotherapy within 8 weeks prior to the first dose.

For the study, patients will be randomly assigned to receive TYRA-300 at either 50 mg once daily (cohort 1) or 60 mg once daily (cohort 2). An additional dosing cohort may be added following a review of safety and efficacy from the first 2 cohorts.

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

"Our goal is to develop TYRA-300 as the first once-daily oral treatment designed to reduce disease recurrence, as well as surgical procedural intervention and intravesical therapy, for people living with IR NMIBC," said Erik T. Goluboff, MD, MBA, SVP of clinical development at TYRA, in the news release.¹ "We believe we are well-positioned to contribute meaningful advancements to the field of bladder cancer with SURF302, and we anticipate that the clinical data will offer valuable insights with the potential to enhance patient outcomes."

Completion of the SURF302 trial is slated for September 2028.

Additional studies of TYRA-300

In addition to the SURF302 trial, TYRA-300 is also under investigation in the phase 1/2 SURF301 study (NCT05544552), evaluating the agent in patients with metastatic urothelial carcinoma and other solid tumors with FGFR3 gene alterations. Preliminary data from the trial were presented at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, in October 2024.³

Overall, TYRA-300 demonstrated promising initial clinical activity while maintaining a favorable tolerability profile in patients with metastatic urothelial carcinoma. In total, 41 patients were included in the preliminary analysis at the time of data cutoff. TYRA-300 was evaluated across 6 dose levels, ranging from 10 mg to 120 mg once daily.

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.

According to the authors, the therapy was also generally well-tolerated. Overall, adverse events (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). There were no grade 4 or higher treatment-related AEs.

The trial is ongoing, with final completion expected in June 2027.⁴

REFERENCES

1. Tyra Biosciences doses first patient in phase 2 study of TYRA-300 in low-grade intermediate risk non-muscle invasive bladder cancer (SURF302). News release. Tyra Biosciences. Published online and accessed June 30, 2025. https://ir.tyra.bio/news-releases/news-release-details/tyra-biosciences-doses-first-patient-phase-2-study-tyra-300-low

2. Efficacy and safety of TYRA-300 in participants with FGFR3 altered low grade, intermediate risk non-muscle invasive bladder cancer (SURF302). ClinicalTrials.gov. Last updated June 5, 2025. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT06995677

3. 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. https://ir.tyra.bio/static-files/7b9782e5-34ac-456c-ba77-e76aa5fab667

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. Last updated October 3, 2024. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT05544552