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ALK L1196M is the gatekeeper mutation conferring resistance to crizotinib but retaining s...

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

IDBMA-ALK-L1196M-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-ALK-FUSION
VariantL1196M (acquired resistance)
DiseaseDIS-NSCLC
ESCAT tierIB
Recommended combinationsalectinib monotherapy, brigatinib monotherapy, lorlatinib monotherapy
Contraindicated monotherapycrizotinib (resistant)
Evidence summaryALK L1196M is the gatekeeper mutation conferring resistance to crizotinib but retaining sensitivity to 2nd-gen ALK-TKIs (alectinib, brigatinib, ceritinib) and to lorlatinib. Historically the most common crizotinib-resistance mutation; less prevalent now that crizotinib is no longer 1L.

Notes

OncoKB R1 (resistance to crizotinib only). Less clinically relevant in the modern era as crizotinib is no longer 1L.

Used By

No reverse references found in the YAML corpus.