Dabogratinib Shows Early Efficacy Signal in FGFR3-Altered NMIBC

Oral dabogratinib (formerly TYRA-300), an investigational FGFR3-selective inhibitor, demonstrated a favorable overall response rate (ORR) in the combined single- and multiple-marker-lesion population in patients with FGFR3-altered low-grade intermediate-risk non-muscle invasive bladder cancer (NMIBC).¹

Findings from SURF302 (NCT06995677), a multicenter, open-label phase 2 trial, identified 60 mg once daily as the dose supporting a planned registrational phase 3 adjuvant trial. Among 14 participants evaluable for efficacy at the 60 mg daily dose in the combined single- and multiple-marker-lesion population, the ORR was 79% (11 of 14) at both the 3-month assessment and as best overall response (BOR), with a complete response (CR) rate of 57% (8 of 14) at 3 months and 64% (9 of 14) as BOR.

Trial Background

SURF302 dosed its first patient in June 2025. The study randomly assigned patients into 2 parallel dose cohorts of 60 mg and 50 mg daily, with a possible third cohort to evaluate alternative dosing pending safety and efficacy data from the initial groups, and planned enrollment of up to 90 patients with FGFR3-altered low-grade intermediate-risk NMIBC, including a documented FGFR3 mutation or fusion and a residual visible marker lesion.

The trial’s primary end point is CR rate at 3 months posttreatment, with recurrence-free survival, progression-free survival, duration of response, time to recurrence, and safety/tolerability as secondary end points. Patients who had a CR at 3 months would continue treatment for up to 24 months; those without a CR could continue if marker lesion reductions are greater than 50%.

Among 44 patients treated at the August 31, 2026 data cutoff, the median age was 70 years, 71% were male, and 91% had an FGFR3 mutation, with the others having an FGFR fusion; 2 had both. Sixty-one percent had no prior intravesical therapy, and 27 (61%) had 1 marker lesion. Across the 50 mg (n = 12) and 60 mg (n = 14) cohorts combined, 26 of 44 treated participants were evaluable for efficacy.²

Additional Efficacy Findings

As of the data cutoff, the ORR was 100% in patients with a single marker lesion treated at 60 mg (n = 8) at 3 months and as BOR, with a CR rate of 63% (5 of 8) at 3 months and 75% (6 of 8) as BOR.¹

In the 50 mg cohort, ORR and BOR in the combined single- and multiple-marker-lesion population was 67% (8 of 12) and CR was 33% (4 of 12) at 3 months. Pooling both dose levels, patients with a single marker lesion (n = 16) had an ORR of 94% (15 of 16) and a CR rate of 50% (8 of 16) at 3 months, rising to 56% (9 of 16) as BOR. All 3-month CRs with available 6-month assessments (n = 5) remained in response at 6 months, and the first participant enrolled in the study remained in CR at 12 months and continued on the study drug at 14 months.

A preliminary exposure-response analysis across the 50 mg and 60 mg cohorts showed an ORR of 86% (12 of 14) among participants with steady-state exposure above an area-under-the-curve threshold of 2500 ng/hour/mL, compared with 58% (7 of 12) below that threshold. The sponsor reported that this exposure-response relationship was most apparent among patients with multiple marker lesions, whereas responses among patients with a single marker lesion occurred across the observed exposure range.

The sponsor proposed that these findings support evaluation at 60 mg in the adjuvant setting and exploration of a higher dose of 70 mg in the ablative setting. “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, stated in a news release.

Safety Findings

As of the data cutoff, safety and tolerability results were reported as favorable across the 60-mg (n = 22) and 50-mg daily dose (n = 22) cohorts. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2; grade 3 TEAEs occurred in 3 participants (14%) at 60 mg and 2 participants (9%) at 50 mg, and grade 3 treatment-related adverse events occurred in 2 of 44 participants (4.5%), both at 50 mg, with none at 60 mg.

No grade 4 or 5 TEAEs were reported. No clinically significant hyperphosphatemia, nail toxicity, or ocular toxicity was observed, transaminase TEAEs occurred at a frequency below 10%, and there were no dose reductions or treatment-related discontinuations at 60 mg. The most frequently reported TEAEs at 60 mg were fatigue, diarrhea, and dry eye, with diarrhea generally grade 1, transient, and limited.

“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 the 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.”

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://tinyurl.com/mr4c563b

2. Conference call and Webcast - Initial Results of Oral Dabogratinib from the SURF302 Phase 2 Study. TYRA Biosciences. September 9, 2026. Accessed September 9, 2026. https://tinyurl.com/yykxb9mc