Dabogratinib Elicits Responses in FGFR3+ Low-Grade Intermediate-Risk NMIBC

The oral FGFR3-selective inhibitor dabogratinib (TYRA-300) generated responses in patients with FGFR3-altered low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC), according to initial results from the phase 2 SURF302 trial (NCT06995677).¹

Findings announced by Tyra Biosciences showed that at the 60-mg, once-daily dose, patients (n = 14) achieved an overall response rate (ORR) of 79% at the 3-month assessment, which included a complete response (CR) rate of 57%. The best ORR at any time with this dose was also 79%, and the best CR rate at any time was 64%. In the 50-mg cohort (n = 12), the 3-month ORR and CR rate were 67% and 33%; these corresponded with the rates of best response at any time.

Among the subset of patients with a single marker lesion who were treated at 60 mg (n = 8), the ORR was 100%, including a CR rate of 75% as best overall response. Across the 50-mg and 60-mg cohorts, patients with a single marker lesion (n = 16) achieved an ORR of 94%. All patients who reached a CR at 3 months and had a 6-month assessment remained in response at 6 months (n = 5), and the first participant enrolled remained in CR at 12 months and continued on treatment at 14 months.

A preliminary exposure-response analysis showed an ORR of 86% among patients above an area-under-the-curve threshold of 2500 ng·h/mL (n = 14) vs 58% among those below it (n = 12), with the relationship most apparent in patients with multiple marker lesions.

Safety data were consistent with dabogratinib's previously reported profile; at the 60-mg dose (n = 22), grade 3 treatment-emergent adverse effects (TEAEs) occurred in 14% of patients, with no grade 3 treatment-related AEs, no dose reductions, and no treatment-related discontinuations reported. No grade 4 or 5 TEAEs occurred. No clinically significant hyperphosphatemia, nail toxicity, or ocular toxicity was observed, and transaminase TEAEs occurred at a frequency of less than 10%. The most frequently reported TEAEs at the 60-mg dose were fatigue, diarrhea, and dry eye, with diarrhea generally grade 1, transient, and limited.

Tyra Biosciences reported plans to complete enrollment in the 60-mg once-daily cohort and to initiate a 70-mg once-daily cohort to explore dabogratinib in an ablative setting. The company added that it intends to engage health authorities on the design and dose selection for a phase 3 study and to prepare for a planned registrational adjuvant trial, subject to regulatory feedback.

“As a community-based urologist, one of the greatest challenges isn't identifying patients who could benefit from therapy—it's that many choose surveillance because the burden of repeated catheterization and intravesical treatments outweighs the perceived benefit,” Mark Silva, MD, of Greater Boston Urology, stated in a news release. “Too often, those patients are simply waiting to recur. A well-tolerated once-daily oral therapy could fundamentally change that conversation, giving patients an option they may be more willing to accept, and giving physicians the chance to intervene before the next recurrence rather than react after it occurs.”

How is SURF302 being conducted?

SURF302 is a phase 2, multicenter, open-label study evaluating the efficacy and safety of dabogratinib in patients with FGFR3-altered low-grade intermediate-risk NMIBC, with an estimated enrollment of 90 patients allocated across dose-optimization cohorts.²

Eligible patients need to be at least 18 years of age with histologically confirmed low-grade Ta or T1 intermediate-risk NMIBC, a residual marker lesion of 3 mm to 12 mm, a documented activating FGFR3 mutation or fusion, and an ECOG performance status of 0 or 1. Those with prior FGFR inhibitor therapy or muscle-invasive, metastatic, or lymph node–positive disease are being excluded.

Patients in dose cohort A are receiving oral dabogratinib at 60 mg once daily, and those in dose cohort B are receiving 50 mg once daily, with a third cohort to be determined based on safety and efficacy data.

The primary end point is CR rate at 3 months; secondary end points include duration of response, time to recurrence, recurrence-free survival at 12 and 24 months, progression-free survival, and safety.

“SURF302 has effectively given us two studies in one, informing dual settings in which dabogratinib could potentially be used,” Doug Warner, MD, chief medical officer of Tyra Biosciences, added in a news release.¹ “Taken together, these data have meaningfully expanded our understanding of dabogratinib as we look to continue to advance development into phase 3 studies.”

References

1. Tyra Biosciences reports initial phase 2 SURF302 results supporting the first potential oral innovation in LG IR NMIBC with dabogratinib. News release. Tyra Biosciences. September 9, 2026. Accessed September 9, 2026. https://ir.tyra.bio/news-releases/news-release-details/tyra-biosciences-reports-initial-phase-2-surf302-results
2. Efficacy and safety of TYRA-300 in participants with FGFR3 altered low grade, intermediate risk non-muscle invasive bladder cancer (SURF302). ClinicalTrials.gov. Updated 2026. Accessed September 9, 2026. https://clinicaltrials.gov/study/NCT06995677