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 2)

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. Repetition of the original experiment. Includes technical replicates for samples previously included and new samples for additional time points