Promising efficacy of next-generation FGFR1-3 inhibitor, Tienegotinib, in heavily pre-treated cholangiocarcinoma patients

Medical News


Abstract: Tinengotinib, a next-generation FGFR1-3 inhibitor, has exhibited promising efficacy in cholangiocarcinoma patients with FGFR2 fusion who have undergone prior treatment with other FGFR inhibitors, as well as in patients with other FGFR alterations (non-fusion). These recent findings were presented at the 2024 ASCO Gastrointestinal Cancers Symposium.

FGFR fusions are found in 10% to 15% of cholangiocarcinoma patients. While several FGFR inhibitors have gained FDA approval for treating cholangiocarcinoma patients with FGFR2 fusion, FGFR mutations may arise as a mechanism of acquired resistance. Unlike first-generation FGFR inhibitors that target the inner pocket of the ATP-binding site where most acquired mutations occur, tinengotinib binds to a site away from the inner pocket to reduce the impact of mutations. It binds specifically to the active configuration of FGFR2 with high affinity through three hydrogen bonds. Preclinical studies have demonstrated tinengotinib's remarkable potency against FGFR kinase domain mutations. In phase 2 trials, patients with FGFR alterations exhibited objective response rates (ORR) of 26.3% and disease control rates (DCR) of 94.7%, respectively. Among patients with acquired resistance to prior FGFR inhibitors, the ORR and DCR were 40% and 90%, respectively. The toxicity and side effects were well-managed and tolerable. These promising findings suggest that tinengotinib could serve as a viable option for cholangiocarcinoma patients resistant to FGFR inhibitors.

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