Combined Inhibition of KRAS G12C and PD1 Boosts Therapeutic Efficacy via Conditioning of Tumor Microenvironment

SITC Poster #466: Mutant KRAS is linked to PD-L1 expression, and oncogenic RAS signaling promotes an immunosuppressive tumor microenvironment by upregulating PD-L1 expression. Consequently, combining KRAS G12C inhibitors with immune checkpoint blockers shows promising benefits. To better understand the mechanisms underlying the combined inhibition of KRAS G12C inhibitor AMG 510, and anti-PD-1 antibody nivolumab, LU-01-0361 tumor models were established using human PBMC or CD34+ cells transplanted into humanized mice. We found that combination therapy of AMG 510 and nivolumab demonstrated significant anti-tumor activities in pre-clinical humanized NSCLC mouse models. Notably, AMG 510 provided complementary immune modulatory benefits that support the mechanism of nivolumab. These findings suggest that combining KRAS G12C inhibitor with anti-PD-1 antibody could be a promising therapeutic strategy for NSCLC patients.

Download our SITC 2023 poster now to learn more about this combinatorial therapeutic approach!