Abstract 7083: ABSK211, a highly potent and orally available pan-KRAS inhibitor, demonstrates robust antitumor efficacy in combination with multiple agents

Abstract Background: KRAS mutations are prevalent oncogenic drivers in pancreatic, lung, and colorectal cancers. Although current KRAS inhibitors have shown promising clinical activity, rational combination strategies may yield greater therapeutic benefit. ABSK211, a highly potent and orally available pan-KRAS inhibitor discovered by Abbisko, represents a promising therapeutic candidate targeting a broad spectrum of KRAS-driven tumors. This study evaluates the preclinical combination potential of ABSK211 with mechanistically diverse agents to enhance anti-tumor efficacy. Methods: In vitro synergistic anti-proliferative effects of ABSK211 were assessed in combination with the MTA-cooperative PRMT5 inhibitors, the EGFR monoclonal antibody (mAb), and chemotherapies across KRAS-mutant pancreatic, lung, and colorectal cancer models. Synergy was quantified using combination index analysis. In vivo efficacy of the combination regimens was assessed in various tumor models to determine tumor growth inhibition and response durability. Results: ABSK211 demonstrated in vitro synergy with the evaluated combination partners in anti-proliferation assays. Pronounced synergy was observed with PRMT5 inhibitor across diverse KRAS mutation contexts. Similarly, combinations with cetuximab or chemotherapy agents showed strong synergy in KRAS G12D and G12V colorectal and pancreatic models. In vivo, combinations of ABSK211 with ABSK131, cetuximab, immunotherapy, or chemotherapy produced markedly enhanced tumor growth inhibition compared with monotherapies in various tumor models. Conclusions: These findings provide a strong preclinical rationale for advancing these combinations of ABSK211 into clinical development to improve outcomes for patients with KRAS-mutant cancers. Citation Format: Qianqian Chen, Bin Shen, Xiao Chen, Jie Wang, Jie Zhang, Manqi Liu, Hongping Yu, Nannan Zhang. ABSK211, a highly potent and orally available pan-KRAS inhibitor, demonstrates robust antitumor efficacy in combination with multiple agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7083.