HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma

This is an open-label, single-arm, multicenter phase 2/3b clinical study to evaluate the efficacy and safety of HMPL-453 tartrate in the treatment of patients with advanced ICC habouring FGFR2 fusions/rearrangements/mutations. The study consists of the following 4 cohorts.

Cohort 1: Approximately 12 patients with locally advanced unresectable or metastatic ICC habouring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance are planned to be enrolled in this cohort to receive HMPL-453 tartrate 150 mg administered orally once daily (QD) continuously in 21-day cycles.

Cohort 2: A total of approximately 113-116 patients are planned to be enrolled in this cohort, divided into safety run-in and extension phases. Approximately 6 to 9 patients with solid tumors who failed standard treatment or had intolerable toxicity will be enrolled into the first phase (safety run-in phase), to receive HMPL-453 tartrate 300 mg QD orally (for 14 consecutive days \[Day 1 to 14\], followed by 7 days off \[Day 15 to 21\], 21 days as a treatment cycle). Dose limiting toxicities (DLT) observation period consists of 28 days, in which a cycle of treatment will be received. Patients will enter second stage of cohort 2 (extension phase) after completion of safety run-in assessments. Approximately 20 patients with locally advanced unresectable or metastatic ICC habouring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance will receive HMPL-453 tartrate 300 mg QD orally administered (for 14 consecutive days \[Day 1 to 14\], followed by 7 days off \[Day 15 to 21\], 21 days as a treatment cycle). Based on the efficacy and safety data of the enrolled patients, and after reaching an agreement with China Center for Drug Evaluation on 17 Feb 2023, approximately 87 patients with locally advanced unresectable or metastatic ICC habouring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance will be enrolled to support registration submission as the registration study stage of this study, receiving HMPL-453 tartrate 300 mg QD orally (for 14 consecutive days \[Days 1 to 14\] followed by 7 days off \[Day 15 to 21\], 21 days as a treatment cycle.

Cohort 3 (Confirmatory Study Cohort): A total of approximately 87 patients with locally advanced unresectable or metastatic ICC harbouring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance are planned to be enrolled in this cohort, as the confirmatory study phase of this study. Patients will receive HMPL-453 tartrate 300 mg QD for 14 days (Days 1 to 14), followed by 7 days off (Days 15 to 21), (21-day treatment cycles).