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EGFR C797S is the principal acquired resistance mutation to osimertinib. Cis-configuratio...

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

IDBMA-EGFR-C797S-NSCLC
TypeActionability
Statusreviewed 2026-04-27 | pending_clinical_signoff | actionability review required
DiseasesDIS-NSCLC
SourcesSRC-CIVIC SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025

Actionability Facts

BiomarkerBIO-EGFR-MUTATION
VariantC797S
DiseaseDIS-NSCLC
ESCAT tierIIB
Recommended combinationsamivantamab + carboplatin + pemetrexed (MARIPOSA-2), platinum-doublet chemotherapy, clinical trial of 4th-gen EGFR-TKI
Contraindicated monotherapyosimertinib monotherapy (resistant), any current 3rd-gen EGFR-TKI alone
Evidence summaryEGFR C797S is the principal acquired resistance mutation to osimertinib. Cis-configuration with T790M renders all currently approved 3rd-gen EGFR-TKIs ineffective; trans-configuration may respond to combination 1st-gen + osimertinib. Investigational 4th-gen EGFR-TKIs (BLU-945, BBT-176) and amivantamab+chemo (MARIPOSA-2) are active options.

Notes

OncoKB R2 (resistance, clinical evidence). Test allelic configuration (cis vs trans) when feasible — guides salvage choice. Trans-C797S/T790M retains sensitivity to gefitinib+osimertinib combo (case-series only).

Used By

No reverse references found in the YAML corpus.