FAK inhibitor and RAF/MEK clamp avutometinib enhance KRAS G12C inhibitor efficacy in preclinical models of non-small cell lung cancer.

Combining FAK inhibitor and RAF/MEK clamp avutometinib with KRAS G12C inhibitor enhances tumor suppression in NSCLC models, surpassing single or double therapies.

• Why it matters: Overcoming resistance to KRAS G12C inhibitors is crucial for improving treatment outcomes in NSCLC patients, as resistance mechanisms limit clinical benefits.
• What they did: Researchers tested a triplet combination of sotorasib, avutometinib, and defactinib in KRAS G12C NSCLC mouse models, including resistant ones, to evaluate antitumor activity and resistance reversal.
• The result: The triplet therapy produced greater tumor growth inhibition, restored sotorasib sensitivity in resistant models, and increased response depth and durability, supporting clinical evaluation of this combination.