Dabogratinib shows early activity in FGFR3-altered LG-IR-NMIBC

Initial findings from the phase 2 SURF302 trial suggest that the investigational oral FGFR3-selective inhibitor dabogratinib may have antitumor activity in patients with FGFR3-altered low-grade, intermediate-risk non–muscle invasive bladder cancer (LG-IR-NMIBC).¹

Dabogratinib, previously designated TYRA-300, is an investigational oral FGFR3-selective inhibitor.

The SURF302 trial explored the agent in LG-IR-NMBC, identifying 60 mg once-daily as the potential dose for a registrational study. Among 14 efficacy-evaluable patients receiving dabogratinib 60 mg once daily, the overall response rate (ORR) was 79% and the best overall response rate for complete response (CR) was 64%, according to results released by Tyra Biosciences, the drug's developer. Among 8 patients with a single marker lesion, the company reported a 100% ORR and a 75% best overall response CR rate at the 60-mg dose.

"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," said Mark Silva, MD, of Greater Boston Urology, in the news release.¹ "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."

SURF302 evaluates oral FGFR3 inhibition

SURF302 is an ongoing, multicenter, open-label phase 2 study evaluating dabogratinib in adults with FGFR3-altered LG-IR-NMIBC.

The current efficacy analysis included 26 participants who had received study treatment and completed at least the month 3 disease assessment. Fourteen patients were receiving 60 mg once daily and 12 were receiving 50 mg once daily.

At 60 mg once daily, the company reported an ORR of 79% (11 of 14 patients) at the 3-month assessment and the same ORR when best overall response was considered. CR at 3 months occurred in 57% of patients (8 of 14), increasing to 64% (9 of 14) for best overall response. The additional CR reflected a patient who initially had a partial response at 3 months and converted to CR at 6 months.

Among patients with a single marker lesion, all 8 patients receiving 60 mg had an overall response, with 5 achieving CR at 3 months (63%) and 6 achieving CR as their best overall response (75%). All 5 patients who had achieved a CR at 3 months remained in response at 6 months, according to the company. The first patient enrolled remained in CR at 12 months and continued treatment at 14 months.

The company also reported an exposure-response analysis. Among participants whose steady-state exposure exceeded an area-under-the-curve threshold of 2500 ng·h/mL, the ORR was 86% (12 of 14), compared with 58% (7 of 12) among those below the threshold. The relationship appeared more pronounced among patients with multiple marker lesions, whereas responses among patients with single marker lesions occurred across the observed exposure range.

According to Tyra, these results “support 60 mg QD in the planned adjuvant setting, where disease burden is minimal, and the evaluation of a higher dose in the ablative setting.” The company said it plans to complete enrollment in the 60-mg cohort and evaluate a 70-mg dose in the ablative setting.

Safety findings

Safety data were available for 44 participants across the 60-mg and 50-mg cohorts (n = 22 in each cohort). Treatment-emergent adverse events (TEAEs) were generally grade 1 or 2. Grade 3 TEAEs occurred in 3 patients (14%) at 60 mg and 2 patients (9%) at 50 mg. Two patients overall (4.5%) experienced grade 3 treatment-related adverse events, both in the 50-mg cohort; none occurred at 60 mg. No grade 4 or grade 5 treatment-emergent adverse events were reported.

There were no dose reductions or treatment-related discontinuations in the 60 mg cohort. Further, there were no reports of clinically significant hyperphosphatemia, nail toxicity, or ocular toxicity. The most frequently reported TEAEs at 60 mg were fatigue, diarrhea, and dry eye, with diarrhea generally described as grade 1, transient, and limited. Transaminase TEAEs occurred in fewer than 10% of participants.

"SURF302 has effectively given us 2 studies in one, informing dual settings in which dabogratinib could potentially be used. Patients with a single marker lesion — whose minimal disease most closely mirrors the adjuvant setting (where no tumor is left behind) and historical marker lesion studies—achieved a 100% ORR (8/8) with 60 mg QD, including a 75% CR rate as best overall response, demonstrating the activity of this dose for our planned phase 3 adjuvant study," said Doug Warner, MD, Chief Medical Officer of Tyra, in the news release.¹ "Patients with multiple marker lesions carry a higher tumor burden, more representative of an ablative setting, and our preliminary exposure-response analyses suggest that higher drug exposure may be important there. Dabogratinib's favorable safety results to date give us the opportunity to evaluate a higher dose in that setting. Taken together, these data have meaningfully expanded our understanding of dabogratinib as we look to continue to advance development into phase 3 studies."

Tyra noted plans to engage regulatory authorities on the design and dose selection for a potential phase 3 registrational study in the adjuvant setting. Dabogratinib is also under investigation in low-grade upper tract urothelial carcinoma in the phase 2 SURF303 trial.

REFERENCE

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