ALK L1196M gatekeeper resistance mutation
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-ALK-L1196M |
|---|---|
| Type | Biomarker |
| Aliases | ALK L1196M gatekeeper mutationALK L1196M — мутація резистентності (gatekeeper)ALK gatekeeperALK p.L1196M |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ALEX-PETERS-2017 SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "23", "functional_impact": "gatekeeper resistance to crizotinib (1st-gen) and partial resistance to alectinib; sensitive to brigatinib, ceritinib, lorlatinib", "gene": "ALK", "hgvs_protein": "p.L1196M", "variant_type": "missense"} |
| Measurement | MethodctDNA NGS at progression; tumor re-biopsy NGS Unitscategorical (positive | negative); VAF % when reported |
| Actionability lookup | {"gene": "ALK", "variant": "L1196M"} |
| Related biomarkers | BIO-ALK-FUSION BIO-ALK-REARRANGEMENT BIO-ALK-G1202R |
Notes
Classical ALK gatekeeper mutation (analogous to EGFR T790M, BCR::ABL1 T315I). Most frequently seen as acquired resistance after crizotinib (1st-gen). 2nd-generation TKIs (alectinib, brigatinib, ceritinib) retain activity — alectinib superiority over crizotinib in 1L (ALEX, Peters 2017) is partly explained by avoidance of L1196M-mediated resistance. Lorlatinib also active. Compound mutations involving L1196M (e.g., L1196M + G1202R) emerge under sequential TKI pressure and require trial-based strategies.
Used By
Biomarker
BIO-ALK-G1202R- ALK G1202R resistance mutation
Red flag
RF-IMT-TRANSFORMATION-PROGRESSION- IMT progression on first-line crizotinib (acquired ALK kinase-domain resistance mutation...