{"entity":{"id":"kras-plus-egfr-crc","kind":"pairing","name":"KRAS G12C inhibitor + anti-EGFR antibody (colorectal)","aka":[],"tldr":"In colorectal cancer, a KRAS blocker alone has little effect because the cell turns EGFR up; adding an EGFR antibody stops that.","summary":"This combination pairs KRAS & RAS inhibitors (the G12C inhibitors Sotorasib and Adagrasib) with an anti-EGFR antibody in Colorectal cancer. The mechanism is that colorectal epithelium has strong EGFR-driven adaptive feedback that reactivates the RAS / RAF / MEK / ERK (MAPK) pathway within hours of KRAS inhibition, so a KRAS blocker alone has little effect and adding an EGFR antibody stops the rebound. Sotorasib plus panitumumab was approved on the phase 3 CodeBreaK 300 trial, which showed a progression-free survival benefit, and adagrasib plus cetuximab was approved on KRYSTAL-1, with response rates considerably higher in combination than with monotherapy. The pairing is a stop on the KRAS roadmap from undruggable to G12C to pan-RAS.","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT05198934: CodeBreaK 300","url":"https://clinicaltrials.gov/study/NCT05198934"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":["sotorasib","adagrasib"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":["codebreak-300"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"kras-inhibitors","b":"egfr","rationale":"Colorectal epithelium has strong EGFR-driven adaptive feedback that reactivates MAPK within hours of KRAS inhibition.","evidence":"Phase 3 (CodeBreaK 300) PFS benefit.","pairingType":"combination"},"route":"/pairings/kras-plus-egfr-crc/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"drug":[{"id":"adagrasib","kind":"drug","name":"Adagrasib","route":"/drugs/adagrasib/"},{"id":"sotorasib","kind":"drug","name":"Sotorasib","route":"/drugs/sotorasib/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"trial":[{"id":"codebreak-300","kind":"trial","name":"CodeBreaK 300","route":"/trials/codebreak-300/"}],"technology":[{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","route":"/technologies/kras-inhibitors/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}],"roadmap":[{"id":"kras-roadmap","kind":"roadmap","name":"KRAS roadmap: undruggable → G12C → pan-RAS","route":"/roadmaps/kras-roadmap/"}]}}