Phase 2 Multicenter Open-Label Study on the Efficacy and Safety of TYRA-300 in FGFR3-Altered Low Grade Intermediate Risk Non-Muscle Invasive Bladder Cancer

The primary objective is to assess the efficacy of oral TYRA-300 in patients with FGFR3‑altered low‑grade, intermediate‑risk non‑muscle invasive bladder cancer, providing data on its therapeutic potential in this molecularly defined subset.

Secondary objectives include:

• Further characterization of the drug’s efficacy to refine clinical benefit estimates.
• Evaluation of the pharmacokinetic profile of TYRA-300 to inform dosing strategies.
• Assessment of the safety and tolerability of TYRA-300, establishing its risk profile in the target population.

The trial enrolled 42 participants diagnosed with Non‑muscle invasive bladder cancer (NMIBC), all of whom were adults aged 18 years or older, comprising both male and female patients; the cohort also included individuals classified as vulnerable according to regulatory definitions. Eligibility required histologically confirmed low‑grade NMIBC within six weeks prior to randomization, an intermediate‑risk disease profile, and a documented activating FGFR3 mutation or fusion. Additional key requirements were adequate bone‑marrow, hepatic, and renal function, an Eastern Cooperative Oncology Group performance status of 0–1, and the absence of upper‑tract urothelial carcinoma, recent intravesical therapy, or recent Bacillus Calmette‑Guérin exposure. Selection was based on recent transurethral resection findings, bladder mapping, and imaging to confirm disease extent. No specific dietary or physical‑activity restrictions were imposed beyond the general health criteria outlined above.

The study is a multicenter, open‑label Phase 2 trial evaluating the efficacy and safety of oral TYRA‑300 tablets in participants with Non-muscle invasive bladder cancer harboring activating FGFR3 alterations and classified as low‑grade, intermediate‑risk disease. After an eligibility screening visit to confirm histology, FGFR3 status, and required laboratory parameters, eligible participants receive the investigational product on Day 1 (baseline). Subsequent scheduled visits occur at month 1, month 3 (primary efficacy assessment of complete response), month 6, month 12, month 24, and a final end‑of‑study visit, each including physical examination, cystoscopic evaluation of the marker lesion, safety laboratory tests, and pharmacokinetic sampling. The intended duration of individual participant involvement is up to 24 months, with overall trial recruitment projected from October 2025 to August 2028. Early termination of a participant’s participation may occur due to unacceptable adverse events, disease progression, withdrawal of consent, or significant protocol non‑compliance, and the study will be concluded for all participants upon completion of the 24‑month follow‑up or earlier if the sponsor determines that continuation is not feasible.

The investigational product, TYRA-300, is formulated as an oral tablet containing 00 mg of the active substance tyra‑300‑b01. The tablet is administered by mouth once daily throughout the treatment period.

This open‑label study does not incorporate a placebo or an alternative comparator; participants receive only the investigational medication without concomitant standard‑of‑care therapy specific to the trial protocol.

Dosing is scheduled for continuous daily administration until predefined study endpoints are reached. Participant adherence is monitored through returned tablet counts and electronic dosing diaries, with site personnel reviewing compliance at each study visit. The trial enrolls individuals diagnosed with low grade, intermediate risk non‑muscle invasive bladder cancer harboring FGFR3 alterations.

Efficacy will be assessed principally by the complete response (CR) rate determined at the 3‑month assessment point. Participants will be evaluated for the presence or absence of disease, and the proportion achieving CR will be calculated.

Secondary efficacy evaluations will include duration of response, time to recurrence, recurrence‑free survival at 12 and 24 months (restricted to responders), and progression‑free survival for the overall cohort. These parameters will be measured at the specified timepoints and analyzed using appropriate time‑to‑event statistical methods.