Multicenter phase 2 trial of tinengotinib for previously treated adults with advanced or metastatic cholangiocarcinoma

Cholangiocarcinoma is an 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. A phase 2 trial at 32 centers in the USA evaluated the multikinase inhibitor tinengotinib 10 mg daily for adult patients with advanced or metastatic cholangiocarcinoma, who previously received systemic chemotherapy and had and EGOG Group score of 0 or 1. Median duration of follow-up was 11.3 months (IQR 6.5-17.3). The primary endpoint was investigator assessed objective response rate. The ORR was 6.3% among 18 patients with FGFR2 fusion with primary FGFR inhibitor resistance, 30.0% among 11 patients with FGFR2 fusions with acquired FGFR inhibitor resistance, 23.1% among 13 patients with other FGFR alterations, and 0% among 13 patients with FGFR wild-type. Grade 3 treatment-related adverse events included hypertension in 31% of patients, palmar-plantar erythrodysesthesia syndrome in 13%, and stomatitis in 11%. Grade 4 TRAEs occurred in 4% (increased lipase and posterior reversible encephalopathy syndrome); there were no grade 5 TRAEs. The authors conclude that tinengotinib might have activity in previously treated adult patients with advanced or metastatic cholangiocarcinoma.