Tinengotinib Demonstrates Strong Antitumor Activity in FGFR-Altered Cholangiocarcinoma

Key Clinical Takeaways:

• Design/Population: In this open-label, multicenter phase 2 trial, researchers evaluated tinengotinib in patients with advanced or metastatic cholangiocarcinoma previously treated with systemic therapy, stratified by FGFR alteration status. 
• Key Outcomes: Tinengotinib demonstrated objective responses in patients with FGFR2 fusions and acquired FGFR inhibitor resistance, as well as in those with other FGFR alterations, with manageable toxicity.
• Clinical Relevance: These results suggest that tinengotinib may represent a therapeutic option for patients with FGFR-altered cholangiocarcinoma after progression on prior FGFR inhibitors and support further evaluation in phase 3 trials.

According to results from a multicenter, phase 2 trial, tinengotinib demonstrates strong antitumor activity in selected patients with advanced cholangiocarcinoma, particularly those with FGFR2 fusions who developed resistance to prior FGFR inhibitor therapy.

“Cholangiocarcinoma is a rare, aggressive cancer often driven by FGFR2 fusions, which are targetable with inhibitors such as pemigatinib and futibatinib…however, resistance frequently develops due to acquired FGFR2 mutations,” stated Milind Javle, MD, MD Anderson Cancer Center, Houston, Texas, and coauthors.

In this open-label trial, 55 patients received 10 mg of tinengotinib in 28-day cycles until disease progression or unacceptable toxicity. Patients were assigned to 1 of 4 cohorts based on FGFR status: FGFR2 fusions with primary FGFR inhibitor resistance (cohort A1; n = 18), FGFR2 fusions with acquired FGFR inhibitor resistance (cohort A2; n = 11), other FGFR alterations (cohort B; n = 13), or FGFR wild type (cohort C; n = 13). The primary end point was objective response rate (ORR). A key secondary end point was safety. 

At a median follow-up of 11.3 months, the ORR was 6.3% in cohort A1, 30% in cohort A2, 23.1% in cohort B, and 0% in cohort C. The most frequently reported grade 3 treatment-related adverse events included hypertension (31%), palmar-plantar erythrodysesthesia syndrome (13%), and stomatitis (11%). Grade 4 treatment-related adverse events occurred in 2 patients and included increased lipase and posterior reversible encephalopathy syndrome. No treatment-related deaths were reported.

“These findings suggest that tinengotinib might have activity in patients with cholangiocarcinoma with FGFR2 fusions that progressed following FGFR inhibitor therapy,” concluded Dr Javle et al. “The data from this phase 2 study supported the initiation of a phase 3 registration trial.” 

Source: 

Javle M, Fountzilas C, Liao CY, et al. Tinengotinib for adults with advanced or metastatic cholangiocarcinoma: A multicentre, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. Published online: December 2, 2025. doi:  10.1016/S2468-1253(25)00230-4