Ifebemtinib (DB17570): A Comprehensive Monograph on a Novel FAK Inhibitor Poised to Redefine Combination Therapy in Solid Tumors

Executive Summary

Ifebemtinib (also known as IN10018 and BI-853520) is an investigational, orally bioavailable, small molecule inhibitor of Focal Adhesion Kinase (FAK) currently in late-stage clinical development for the treatment of various solid tumors. As a highly potent and selective, ATP-competitive inhibitor of FAK, Ifebemtinib targets a critical signaling node involved in tumor cell proliferation, survival, migration, and invasion. While early studies of Ifebemtinib as a monotherapy demonstrated a manageable safety profile but only modest clinical activity, its development has strategically pivoted towards a combination-centric approach. This strategy is founded on a strong biological rationale that FAK inhibition can overcome intrinsic and acquired resistance to other anticancer agents by both directly targeting tumor cells and modulating the tumor microenvironment.

The clinical data for Ifebemtinib in combination regimens have been exceptionally compelling, positioning the drug as a potential "synergistic anchor" capable of significantly enhancing the efficacy of other therapies. The most profound results have been observed in KRAS G12C-mutant malignancies. In first-line non-small cell lung cancer (NSCLC), the combination of Ifebemtinib with the KRAS G12C inhibitor garsorasib produced an unprecedented objective response rate (ORR) of over 90% and a median progression-free survival (mPFS) exceeding 22 months, representing a potential paradigm shift for this patient population. In previously treated colorectal cancer (CRC), the addition of Ifebemtinib to garsorasib nearly doubled the ORR compared to garsorasib monotherapy. Promising activity has also been demonstrated in platinum-resistant ovarian cancer (PROC) in combination with pegylated liposomal doxorubicin, leading to a registrational trial.