P2, N=14, Recruiting, Amgen | Not yet recruiting --> Recruiting

P2, N=10, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Mar 2027 --> Jan 2026 | Trial primary completion date: Mar 2027 --> Jan 2026

P1/2, N=257, Recruiting, Sichuan Huiyu Pharmaceutical Co., Ltd | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

CXCL1/CXCR2 and HGF/c-MET may represent compensatory pathways that sustain proliferation and survival in resistance to KRASG12C inhibitors. The simultaneous blockade of these signals may offer a novel strategy for bypassing resistance.

P2, N=68, Active, not recruiting, ETOP IBCSG Partners Foundation | Trial primary completion date: Dec 2025 --> Jul 2025

In addition, rivaroxaban and sotorasib were well tolerated by the healthy subjects. These results suggest that rivaroxaban can be safely co-administered without the need for switching to another treatment or dose adjustments in patients treated with sotorasib.

P1, N=191, Completed, Eli Lilly and Company | Recruiting --> Completed

P1, N=16, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P1/2, N=42, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P1/2, N=29, Completed, Jacobio Pharmaceuticals Co., Ltd. | Recruiting --> Completed | N=100 --> 29 | Trial completion date: Jul 2025 --> Feb 2025 | Trial primary completion date: Jan 2024 --> Feb 2025

With further research, recently, targeted drugs targeting the KRASG12C gene mutation have achieved significant breakthroughs in clinical trials, especially the application of KRASG12C-specific inhibitors adagrasib and sotorasib, which has changed the treatment landscape for NSCLC patients. To address challenges such as tumor heterogeneity, the complexity of the tumor microenvironment, interpatient variability, and acquired drug resistance mechanisms, combination therapy strategies involving KRASG12C inhibitors have emerged sequentially. This article systematically reviews the progress of targeted therapy for KRASG12C-mutant NSCLC and the results of related clinical trials, while exploring novel therapeutic strategies for patients with KRASG12C mutations, aiming to provide a reference for the selection of clinical treatment regimens.

Notably, co-targeting ERBB and AURK effectively overcame resistance in afatinib- and sotorasib-refractory models, wherein bypass activation of EGFR, ERK, and AURK was observed. Given the limited survival benefit associated with KRAS-targeted therapies and rapid emergence of resistance in clinical settings, our findings establish ERBB/AURK co-inhibition as a promising therapeutic strategy to improve durability of response and combat acquired resistance in KRAS driven LUAD.