Tinengotinib Efficacy in Patients With Advanced Cholangiocarcinoma: A Phase 2 Trial

Tinengotinib is a multikinase inhibitor that selectively targets a range of kinases and possesses distinctive binding characteristics to a fibroblast growth factor receptor (FGFR). In preclinical models, it has shown the potential to inhibit FGFR2 fusions and rearrangements, as well as mutations associated with acquired resistance and gatekeeper alterations. Furthermore, in phase 1/2 clinical trials, it demonstrated antitumor efficacy in patients with cholangiocarcinoma (CCA).

A recent phase 2 clinical trial presented at the 2025 ASCO Gastrointestinal Cancers Symposium investigated the efficacy of tinengotinib in patients with advanced or metastatic CCA. The study enrolled eligible patients who had received at least 1 prior systemic chemotherapy divided into 4 cohorts based on their FGFR alteration status. Cohort A1 included patients with FGFR2 fusions who had primary progression on a previous FGFR inhibitor. Cohort A2 included patients with FGFR2 fusions who progressed after prior response to an FGFR inhibitor. Cohort B included patients with FGFR alterations but without FGFR2 fusions. Cohort C included patients with FGFR wild-type tumors.

The study enrolled a total of 55 patients: 18 to cohort A1, 11 to cohort A2, 13 to cohort B, and 13 to cohort C. The trial included patients with a median age of 62 years, and an ECOG performance status of 0 to1.

Patients with FGFR2 fusions who were refractory or relapsed from prior FGFR inhibitors demonstrated a median overall survival (OS) of 18 months after treatment with tinengotinib with a median follow-up time of 8.6 months. The median OS varied significantly across the cohorts. Cohort A had a median OS of 18.0 months (95% confidence interval [CI], 9.6-Not Available). The median OS for cohort B was not reached (95% CI, 8.0-Not Available), and cohort C had a median OS of 6.5 months (95% CI, 4.8-16.4).

This study also explored the correlation between genomic alterations and treatment outcomes using circulating tumor DNA analysis (n=46). Patients with MED12 alterations showed a significantly longer progression-free survival (PFS; P=.031). Patients without ARID1A and MET alterations showed a significantly improved PFS (P=.0085 and P=.011, respectively).

This phase 2 trial suggests that tinengotinib demonstrates promising antitumor efficacy in patients with CCA with FGFR fusions after prior FGFR inhibitor therapy, and in those with primary FGFR mutations. A randomized phase 3 study is currently underway to investigate tinengotinib versus chemotherapy in FGFR inhibitor–refractory CCA.

Source:

Fountzilas C, Liao C, Pelster M, et al. Tinengotinib in patients with advanced, metastatic cholangiocarcinoma: overall survival results and biomarker correlative analysis from a phase 2 clinical trial. Presented at: ASCO Gastrointestinal Cancers Symposium. January 23-25, 2025; San Francisco, CA; Virtual. Poster D9.