KRAS G12C

P2, N=86, Recruiting, Abbisko Therapeutics Co, Ltd | Not yet recruiting --> Recruiting

Mouse embryonic fibroblasts transformed with KRASG12C also contain more saturated lipids than KRASG12D MEFs. Thus, activities of KRAS mutants depends on lipid acyl chain remodeling in an allele-specific manner.

This regimen is highly clinically accessible and may serve as a second-line treatment option when KRAS G12C-specific inhibitors are unavailable. Its clinical value requires further validation through large-sample prospective studies.

Although recent advances have led to covalent inhibitors such as Sotorasib and Adagrasib for the KRAS G12C mutation, effective therapies for other common variants, particularly KRAS G12D, which is highly prevalent in aggressive pancreatic cancers, remain limited...To further validate the predictive capability of the models, two compounds identified as high-confidence candidates, Cobimetinib and Etrasimod, were selected for experimental evaluation...While additional biochemical and pathway-level studies are required to confirm direct target engagement, these results support the model's utility in prioritizing candidate compounds with allele-specific activity profiles. Overall, this study provides a data-driven framework for identifying potential KRAS-targeted therapies and highlights the value of integrating machine learning predictions with experimental validation.

P1/2, N=94, Not yet recruiting, Gilead Sciences Inc.

P2/3, N=27, Not yet recruiting, Merck Sharp & Dohme LLC

KRAS G12C-mutant non-small cell lung cancer (NSCLC) has transitioned from a therapeutically problematic disease to a precision-targetable cancer, anchored by the landmark approvals of sotorasib and adagrasib. We further highlight patient-derived 3D models, multi-omics technologies, and ctDNA-guided monitoring as essential translational platforms. Finally, we propose an integrated translational roadmap that combines mechanistic insights with clinical innovation, offering new directions for precision therapy and improved patient outcomes in KRAS-driven NSCLC.

Integration of human cancer cell line essentiality data and adult mouse loss-of-function phenotypes provided a complementary tolerability layer to refine prioritization. ResMap establishes a foundation for coordinated community efforts to accelerate rational persister-directed combination strategies toward the clinic.

P1/2, N=190, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: May 2037 --> Apr 2032

P3, N=195, Recruiting, InnoPharmax Inc. | Not yet recruiting --> Recruiting

Invitae and Fulgent offer the broadest gene coverage (20/21), with 16 genes universally covered by all four providers, while GeneD and Prevention Genetics lag at 17 genes each, with critical gaps in rare cancer predisposition genes like TSC1, TSC2, and NF1. Overall, these findings refine the molecular landscape of PC and highlight key genes and pathways with potential clinical relevance.

P1/2, N=75, Not yet recruiting, Gilead Sciences Inc.