Abstract Background: Sotorasib, a KRAS G12C inhibitor, plus panitumumab is approved for use in chemorefractory metastatic colorectal cancer (mCRC) . Yet, early effects on the tumor microenvironment (TME) in clinical samples are not well understood. In preclinical models, sotorasib potently suppresses MAPK signaling and promotes a pro-inflammatory TME characterized by CD8+ T cell infiltration and increased IFN-γ activity, implicating adaptive immunity in tumor control. We investigated if these pharmacodynamic and immunologic effects are observed clinically in patients (pts) treated with sotorasib plus panitumumab. Methods: Paired biopsies before and after 3-4 weeks of sotorasib plus panitumumab treatment were available from 12 pts in Cohort A of CodeBreaK 101 (NCT04185883). We performed whole-transcriptome RNA sequencing (n=12), pERK immunohistochemistry (n=8), spatial analysis of H Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2929.
Hong et al. (Fri,) studied this question.
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