In a phase 2 study, the novel, FGFR1/2/3-selective tyrosine kinase inhibitor (TKI) HMPL-453 showed promising efficacy with acceptable toxicity among patients with advanced intrahepatic cholangiocarcinoma with FGFR2 fusions.

This single-arm, multi-cohort, open-label phase 2 trial, included 25 patients with advanced or metastatic intrahepatic cholangiocarcinoma with FGFR2 fusions who had previously been treated with ≥1 line of systemic therapy. Patients received either 150mg every day (cohort 1; n = 12) or 300mg every day for 2 weeks followed by 1 week off (cohort 2; n = 13) of HMPL-453 until disease progression or intolerable toxicity. The primary end point of this study was objective response rate (ORR), with disease control rate, duration of response, progression-free survival and safety as secondary end points.

At the data cutoff date of September 21, 2022, the median follow-up duration was 12 months for cohort 1 and 4.1 months for cohort 2. Of the 25 total patients, 22 were evaluable (12 in cohort 1, 10 in cohort 2). As determined by investigator assessment, the ORR was 31.8%, with 7 patients achieving a partial response. An additional 12 patients achieved stable disease for a disease control rate of 86.4%. In cohort 2 alone, the ORR was 50% and the disease control rate was 90%. The duration of response was not reached for either cohort. The median progression-free survival 5.7 months in cohort 1 and was not matured for cohort 2.

The most common treatment-related adverse events of any grade were diarrhea, dry mouth, and increased blood phosphorous. The most common grade ≥3 treatment-related adverse events were increased neutrophil count, nail toxicities, and palmar-plantar erythrodysesesia syndrome.

The study authors concluded, “These results warrant further study in patients with advanced [intrahepatic cholangiocarcinoma].”

Source:

Xu J, Xiong J, Gu S, et al. A phase 2 study of HMPL-453, a selective FGFR tyrosine kinase inhibitor (TKI), in patients with previously treated advanced cholangiocarcinoma containing FGFR2 fusions. J Clin Oncol. 2023;41(suppl 16):e16118. doi:10.1200/JCO.2023.41.16_suppl.e16118