Abstract 382: Synergistic anti-tumor effect of ABN401 in combination with KRAS inhibitor in a c-MET-altered KRASG12C non-small cell lung cancer model

Abstract

Abstract ABN401, a highly selective c-MET inhibitor, is being evaluated for the treatment of non-small cell lung cancer (NSCLC) in clinical trials. NSCLC is a heterogeneous in nature and leading cause in cancer related mortality. Numerous studies are still ongoing to identify the key oncogenic mutations that promote tumor progression. Various actionable genetic mutations such as EGFR, ALK, BRAF, MET, RET, and NTRK/ROS1 have been identified, and the targeted therapies are being developed. It is known that targeted therapies can control disease progression in NSCLC patients and drug resistance due to their heterogeneity remains a clinical hurdle. Among the targets, KRAS gene mutations, an unactionable and is now considered a promising therapeutic approach for NSCLC. Currently, co-occurrence of KRASG12C mutation has been reported in NSCLC patients with MET alterations. Moreover, oncogenic KRAS protein can induce c-MET expression levels by signaling pathways. In this study, we aim to provide an alternative therapeutic strategy for NSCLC patients with KRASG12C mutation harboring MET alterations. We have performed several in vitro and in vivo efficacy studies for the combination of ABN401, c-MET inhibitor, and sotorasib, KRASG12C variant inhibitor, including a PDX model of c-MET-altered KRASG12C NSCLC. Our results suggest that the combination of ABN401 and KRAS inhibitor could be an alternative treatment option for c-MET-altered KRASG12C NSCLC patients. Citation Format: Saehyung Lee, Sunghwan Cho, Na Young Kim, Rajasekaran Nirmal, Kyung Eui Park, Jun Young Choi. Synergistic anti-tumor effect of ABN401 in combination with KRAS inhibitor in a c-MET-altered KRASG12C non-small cell lung cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 382.