A multicenter, open-label phase 1/2 study of TYRA-300 in advanced urothelial carcinoma and other solid tumors with activating FGFR3 alterations (SURF301).

Abstract

TPS904 Background: Activating FGFR3 gene alterations have been identified in up to 20% of advanced/metastatic urothelial cancers (mUC). The pan-FGFR inhibitor erdafitinib (erda) is approved for the treatment of mUC with susceptible FGFR3 genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy. Since pan-FGFR inhibitors target all four isoforms of FGFR (1-4), their lack of FGFR isoform specificity can lead to off-target toxicity (e.g., hyperphosphatemia, stomatitis, ocular toxicity, skin and nail toxicity) and loss of activity due to development of on-target resistance mutations (e.g., V555M/L gatekeeper). TYRA-300 has been designed to be more selective for FGFR3 over FGFR1/2/4 to minimize off-target toxicity and to avoid interactions with known FGFR3 gatekeeper mutations. TYRA-300 is in development for the treatment of FGFR3 + mUC and other solid tumors (SURF301 - NCT05544552). Methods: SURF301 is a first-in-human, open-label, Phase 1/2 global study in several parts: dose escalation in participants with advanced malignancies, with/without FGFR3 alterations (Phase 1, Part A); dose expansion in participants with FGFR3 -activating mutations or fusions (Phase 1, Part B); and select tumor expansion cohorts with FGFR3 activating mutations or fusions (Phase 2). The purpose of Phase 1 is to evaluate the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity of TYRA-300, and identify the recommended Phase 2 dose (RP2D). Phase 2 will enroll participants in FGFR3 + mUC and other tumor types to further explore the anti-tumor activity and safety of TYRA-300. SURF301 study began enrolling patients in November 2022 and is ongoing in Australia, the United States, France, and Spain. Clinical trial information: NCT05544552 .