Combination of a SOS1-KRAS interaction inhibitor with a KRASG12C inhibitor combination can address intrinsic and acquired resistance leading to stronger and more durable response (Quant-Seq).

To investigate the transcriptomic changes associated with KRAS G12C inhibitor Adagrasib resistance and Adagrasib + SOS1 inhibitor (BI-3406) or Adagrasib + EGFR inhibitor (Cetuximab) combination treatment to overcome resistance. We performed differential gene expression analysis using RNA-seq generated from cell line derived xenograft (CDX) in vivo models. We compared different treatment conditions with DMSO treated condition. Overall design: CDX models were generated using NSCLC cell line NCI-H2122 and CRC cell line SW837. For each CDX category, expression data with DMSO treated and either single agent and combination treatment was generated.