# KRAS G12C inhibitor + anti-EGFR antibody (colorectal)

Source: https://onco.cc/pairings/kras-plus-egfr-crc/  
OnCo record `kras-plus-egfr-crc` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Pairing
- Last checked: 2026-09-04
- Pairs: KRAS & RAS inhibitors + EGFR
- Type: combination
- Rationale: Colorectal epithelium has strong EGFR-driven adaptive feedback that reactivates MAPK within hours of KRAS inhibition.
- Evidence: Phase 3 (CodeBreaK 300) PFS benefit.

## Sources

- ClinicalTrials.gov NCT05198934: CodeBreaK 300: https://clinicaltrials.gov/study/NCT05198934

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- drugs: [Adagrasib](https://onco.cc/drugs/adagrasib/), [Sotorasib](https://onco.cc/drugs/sotorasib/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- trials: [CodeBreaK 300](https://onco.cc/trials/codebreak-300/)
- technologies: [KRAS & RAS inhibitors](https://onco.cc/technologies/kras-inhibitors/)
- targets: [EGFR](https://onco.cc/targets/egfr/)
- roadmaps: [KRAS roadmap: undruggable → G12C → pan-RAS](https://onco.cc/roadmaps/kras-roadmap/)

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JSON: https://onco.cc/api/v1/entities/kras-plus-egfr-crc.json