EGFR C797S — covalent-binding-site mutation that confers acquired resistance to osimertin...

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

ID	`RF-NSCLC-EGFR-C797S-RESISTANCE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-MARIPOSA2-PASSARO-2024` `SRC-NCCN-NSCLC-2025`

Red Flag Origin

Definition	EGFR C797S — covalent-binding-site mutation that confers acquired resistance to osimertinib (~20% of post-osimertinib progression). 3L+ treatment shifts to amivantamab + lazertinib + chemo (MARIPOSA-2) or chemotherapy. Trans-allelic C797S/T790M relative to the sensitizing mutation predicts whether 1st/3rd-gen EGFR-TKI rotation can recover response.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-NSCLC-METASTATIC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "egfr_c797s",
      "value": true
    },
    {
      "finding": "egfr_c797s",
      "value": "positive"
    },
    {
      "finding": "egfr_mutation",
      "value": "C797S"
    }
  ],
  "type": "biomarker"
}

Notes

Allele context matters: cis-C797S/T790M (same allele) — no available EGFR-TKI restores response, switch to amivantamab + lazertinib + chemo or chemo + bev. Trans-C797S/T790M (different alleles) — combination of 1st-gen + 3rd-gen EGFR-TKI may suppress both clones; rare in practice. Brigatinib + cetuximab data emerging. Note: BIO-EGFR-C797S is not currently authored as a standalone biomarker — finding key egfr_c797s used here for profile match.

Used By

Algorithms

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