Abstract 2929: Immune and pharmacodynamic effects of sotorasib plus panitumumab in KRAS G12C-mutant colorectal cancer: Paired biopsy results from CodeBreaK 101.
Key Points
Investigate the pharmacodynamic and immunologic effects of sotorasib plus panitumumab in KRAS G12C-mutant colorectal cancer.
Conducted paired biopsies before and after 3-4 weeks of treatment.
Performed whole-transcriptome RNA sequencing on 12 samples.
Analyzed pERK expression through immunohistochemistry.
Used digital pathology for spatial analysis of tumor samples.
Employed Wilcoxon signed-rank tests for data comparisons.
MAPK Pathway Activity Score showed an approximate 4-fold reduction.
pERK expression decreased by 1.8-fold in tumor nuclei.
Marked increase in Tumor Inflammation Signature score by 1.9-fold.
Digital pathology indicated increased immune cell clustering in the tumor microenvironment.
Single-cell spatial analysis confirmed presence of activated CD8+ T cells.
Abstract
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.
Like
Bookmark
Share
Like
Bookmark
Share
Abstract 2929: Immune and pharmacodynamic effects of sotorasib plus panitumumab in KRAS G12C-mutant colorectal cancer: Paired biopsy results from CodeBreaK 101. | Synapse