Kinnate Biopharma Inc. announced that the U.S Food and Drug Administration (FDA) has cleared the company's Investigational New Drug (IND) application for KIN-3248, a next-generation pan-FGFR inhibitor being developed for intrahepatic cholangiocarcinoma (ICC) and urothelial carcinoma (UC). KIN-3248 is an irreversible, small molecule pan-FGFR inhibitor that has been developed to address both primary FGFR2 and FGFR3 oncogenic alterations and those predicted to drive acquired resistance to current FGFR-targeted therapies, including gatekeeper, molecular brake, and activation loop mutations observed in cancers such as ICC and other gastrointestinal cancers. In preclinical studies, KIN-3248 demonstrated inhibitory activity across a wide range of clinically relevant mutations that drive primary disease and acquired resistance.

The Phase 1 trial is expected to initiate in the first half of 2022 and will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-cancer activity of KIN-3248 in FGFR inhibitor naïve and pretreated cancer patients with FGFR2 and/or FGFR3 gene alterations. The dose escalation portion (Part A) of the trial will determine the recommended dose and schedule of KIN-3248 for further evaluation in patients with FGFR2 and/or FGFR3 gene alterations. The dose expansion phase (Part B) of the trial will assess the safety and efficacy of KIN-3248 at the recommended dose and schedule in FGFR inhibitor naïve and pretreated patients with cancers driven by FGFR2 and/or FGFR3 gene alterations, including ICC, UC and other selected adult solid tumors.

Oncogenic FGFR (FGFR1, FGFR2, FGFR3, and FGFR4) gene alterations are observed in approximately 7% of all human cancers. FGFR2 gene fusions and FGFR3 activating alterations are predicted oncogenic drivers in approximately 10-20% of cholangiocarcinoma and 20-35% of urothelial cancers, respectively. While currently approved FGFR inhibitors and those in development provide clinical benefit in these cancer indications, disease progression typically occurs within 6-12 months of starting treatment and is often associated with the emergence of on-target resistance mutations within the FGFR kinase domain.