A multicenter, open-label, first-in-human study of TYRA-200 in advanced intrahepatic cholangiocarcinoma and other solid tumors with activating <i>FGFR2</i> gene alterations (SURF201).

TPS646 Background: Approved Fibroblast Growth Factor Receptor (FGFR) inhibitors have demonstrated clinical benefit in locally advanced or metastatic cholangiocarcinoma harboring oncogenic FGFR2 fusions or other rearrangements. However, the emergence of acquired resistance mutations limits the clinical activity and duration of responses to currently available inhibitors. TYRA-200 is an orally bioavailable FGFR1/2/3 inhibitor designed to specifically address these clinically observed acquired resistance alterations in FGFR2. Methods: SURF201 is a single arm, multicenter, open-label, first-in-human, dose escalation and expansion study designed to investigate TYRA-200 in patients (pts) with advanced intrahepatic cholangiocarcinoma and other solid tumors with primary activating FGFR2 gene alterations and on-target acquired known FGFR2 resistance mutations. The study is being conducted in two parts. Part A dose escalation uses an i3+3 design and is evaluating the safety, tolerability, and the pharmacokinetic profile of TYRA-200. Part B dose expansion will further characterize the safety profile and evaluate the preliminary anti-tumor activity of TYRA-200 by RECIST v1.1 in pts with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma who have previously received an FGFR inhibitor(s) and have developed acquired FGFR2 kinase domain resistance mutations. The study is currently planned for approximately four centers in the US and is actively enrolling (NCT06160752). Clinical trial information: NCT06160752 .