KRAS G12C mutation — ~13% of NSCLC adenocarcinoma; smoking-associated. Sotorasib (CodeBre...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-NSCLC-KRAS-G12C-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-CODEBREAK200-JOHNSON-2023` `SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-KRYSTAL1-JANNE-2022` `SRC-NCCN-NSCLC-2025`

Red Flag Origin

Definition	KRAS G12C mutation — ~13% of NSCLC adenocarcinoma; smoking-associated. Sotorasib (CodeBreaK 200 — mPFS 5.6 vs 4.5 mo docetaxel) and adagrasib (KRYSTAL-1) are 2L+ FDA-approved covalent G12C inhibitors. 1L is still IO ± chemo per PD-L1 (no 1L G12C-inhibitor superiority yet).
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-NSCLC-METASTATIC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "kras_g12c",
      "value": true
    },
    {
      "finding": "kras_g12c",
      "value": "positive"
    },
    {
      "finding": "kras_mutation",
      "value": "G12C"
    }
  ],
  "type": "biomarker"
}

Notes

Adagrasib has CNS activity (KRYSTAL-1B brain-met cohort). Hepatotoxicity on sotorasib + concurrent ICI — sequential dosing or G12C monotherapy preferred. Other KRAS variants (G12D, G12V, Q61) NOT actionable with current G12C inhibitors; pan-RAS / G12D-selective agents (RMC-6236, MRTX1133) in trials.

Used By

Algorithms

ALGO-NSCLC-METASTATIC-2L - ALGO-NSCLC-METASTATIC-2L