A phase 2 multicenter, open-label study evaluating the efficacy and safety of dabogratinib (TYRA-300) in participants with FGFR3-altered low-grade, intermediate risk non-muscle invasive bladder cancer (SURF302).

TPS886 Background: Intermediate risk non-muscle invasive bladder cancer (IR NMIBC) is characterized by a high prevalence of activating fibroblast growth factor receptor 3 (FGFR3) mutations and fusions, with up to 80% of cases harboring these alterations (Szklener, 2022). FGFR signaling has been shown to play a crucial role in tumorigenesis and progression of cancer. Targeting FGFR3 may be particularly relevant in IR NMIBC, where novel therapeutic approaches are needed to reduce recurrence and progression. Recently, several pan-FGFR inhibitors have received regulatory approvals across multiple cancers, including erdafitinib in advanced urothelial carcinoma. These compounds are limited by tolerability due to a wide array of adverse events due to nonspecific inhibition. Dabogratinib is a highly selective inhibitor of FGFR3 with significantly lower activity against FGFR1, FGFR2, and FGFR4. Dabogratinib was designed to be selective for FGFR3 and less potent for the other FGFR isoforms, which may offer a differentiated safety profile suitable for the IR NMIBC setting. Methods: SURF302 (NCT06995677) is an open-label, Phase 2, global study that is designed to explore oral dabogratinib as monotherapy in patients with low grade IR NMIBC with activating FGFR3 pathway alterations. Adult patients with confirmed low grade IR NMIBC, at least 1 marker lesion, documented FGFR3 mutation or fusion, no evidence of upper tract disease and adequate organ function are generally eligible. Participants with a history of muscle invasive bladder cancer or metastatic disease, have presence of disease in the ureter or prostatic urethra or have received prior FGFR inhibitor therapy are excluded. The primary endpoint is the 3-month complete response rate in this population. Additional secondary endpoints include duration of response, safety and tolerability, and recurrence-free survival. Two doses will be initially tested (50 and 60 mg QD, n=30 each) in a randomized fashion. The study is planned for approximately 36 centers in North America, Australia, and Europe. Clinical trial information: NCT06995677 .