Dabogratinib Shows Early Activity in FGFR3-Altered Low-Grade NMIBC

Treatment with the oral FGFR3-selective inhibitor dabogratinib (TYRA-300) elicited responses and demonstrated a favorable safety profile in patients with FGFR3-altered low-grade intermediate-risk non-muscle invasive bladder cancer (LG IR NMIBC), according to initial results from the phase 2 SURF302 trial (NCT06995677) shared in a news release from developer Tyra Biosciences.¹

As of the August 31, 2026, data cutoff, 26 patients were evaluable for efficacy, defined as those who received study treatment and completed at least the month 3 disease assessment. Among all patients with single or multiple marker lesions in the 60 mg once-daily cohort (n = 14), the overall response rate (ORR) at the 3-month assessment was 79% (11/14), which included complete responses (CRs) in 57% (8/14) and partial responses (PRs) in 21% (3/14). The best overall response (BOR) CR rate in this cohort was 64% (9/14), which accounted for 1 patient whose 3-month PR converted to a CR at the 6-month assessment; the BOR PR rate was 14% (2/14). In the 50 mg once-daily cohort (n = 12), the ORR at both the 3-month assessment and as BOR was 67% (8/12), with CRs in 33% (4/12) and PRs in 33% (4/12).

Among patients with a single marker lesion who received 60 mg once daily (n = 8), the ORR was 100% (8/8) at 3 months and as BOR. The CR rate in this subgroup was 63% (5/8) at 3 months and 75% (6/8) as BOR, with respective PR rates of 38% (3/8) and 25% (2/8). When both doses were pooled (n = 16), patients with a single marker lesion had an ORR of 94% (15/16) at 3 months and as BOR, with CR rates of 50% (8/16) and 56% (9/16), respectively.

All 5 patients who achieved a CR at 3 months and reached the 6-month assessment remained in response at 6 months. The first patient enrolled in the study remained in CR at 12 months and continued to receive study drug at 14 months. The developer noted that all responses may change with continued treatment and follow-up.

According to Doug Warner, MD, chief medical officer of Tyra Biosciences, the trial has effectively provided data for 2 potential settings. He explained that patients with a single marker lesion have minimal disease that most closely resembles the adjuvant setting and historical marker lesion studies, and that the 100% ORR observed at 60 mg once daily in this group supports the dose for the company’s planned phase 3 adjuvant study. Patients with multiple marker lesions, he added, carry a higher tumor burden that is more representative of an ablative setting, where preliminary exposure-response analyses suggest higher drug exposure may be important.

Across the 50 mg and 60 mg cohorts, patients with a target steady-state exposure above the AUC threshold of 2500 ng•hr/mL had an ORR of 86% (12/14) vs 58% (7/12) among those below the threshold. The exposure-response relationship was most apparent in patients with multiple marker lesions, whereas responses in patients with a single marker lesion occurred across the observed exposure range. The drug’s developer plans to complete enrollment in the 60 mg once-daily cohort, initiate a 70 mg once-daily cohort to evaluate the agent in the ablative setting, and engage health authorities on phase 3 study design and dose selection ahead of a planned registrational adjuvant study.

Regarding safety, initial results were favorable across the 60 mg (n = 22) and 50 mg (n = 22) cohorts. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2; grade 3 TEAEs occurred in 3 patients (14%) at 60 mg and 2 patients (9%) at 50 mg. Grade 3 treatment-related AEs were reported in 2 of 44 patients (4.5%) across both cohorts, both of whom received 50 mg, with none at 60 mg. No grade 4 or 5 TEAEs occurred, and there were no dose reductions or treatment-related discontinuations at 60 mg.

Investigators observed no clinically significant hyperphosphatemia, nail toxicity, or ocular toxicity. Transaminase TEAEs occurred at a frequency of less than 10%. The most common TEAEs at 60 mg were fatigue, diarrhea, and dry eye; diarrhea was generally grade 1, transient, and limited.

“A well-tolerated once-daily oral therapy could fundamentally change that conversation,” said Mark Silva, MD, of Greater Boston Urology, referring to patients who choose surveillance because the burden of repeated catheterization and intravesical treatment outweighs its perceived benefit. He noted that such an option could allow physicians to intervene before the next recurrence rather than react after it.

The developer stated that approximately 70% of patients with LG IR NMIBC do not receive adjuvant therapy intended to reduce recurrence despite evidence that intravesical treatment lowers recurrence risk. Current treatment typically consists of transurethral resection of bladder tumor followed by intravesical chemotherapy delivered via repeated bladder catheterization.

SURF302 is a multicenter, open-label phase 2 study sponsored by Tyra Biosciences that includes dose-optimization cohorts and is designed to support the potential development of dabogratinib as an adjuvant therapy.²

Key end points include BOR, CR at 3 months, time to recurrence, duration of response, recurrence-free survival, progression-free survival, and safety and tolerability. The study began on June 27, 2025, and is currently recruiting, with an estimated primary completion date of February 2028 and an estimated study completion date of September 2028.²

Additionally, the developer reported that the first patient treated in SURF303, a phase 2 study of dabogratinib in low-grade upper tract urothelial cancer, achieved a CR at the 3-month assessment with 60 mg once daily, experienced no TEAEs, and remained on study drug as of the data cutoff.¹

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, Inc. September 9, 2026. Accessed September 10, 2026. https://tinyurl.com/3y5ktzv4

2. Efficacy and safety of TYRA-300 in participants with FGFR3 altered low grade, intermediate risk non-muscle invasive bladder cancer. ClinicalTrials.gov. Updated February 2026. Accessed September 10, 2026. https://tinyurl.com/mry55ewr