ALK fusion (ALK-positive)
An ALK fusion, usually EML4::ALK, is a swapped piece of chromosome 2 that turns the ALK kinase on permanently in about 4 percent of lung adenocarcinomas. Seven ALK inhibitors are approved for it, including alectinib after surgery.
Overview
ALK rearrangements are detected by break-apart FISH (Vysis), immunohistochemistry (Ventana D5F3), or DNA and RNA sequencing; the FDA list carries all three routes as companion diagnostics. Crizotinib, ceritinib, alectinib, brigatinib, lorlatinib and ensartinib are labelled for ALK-positive metastatic NSCLC 'as detected by an FDA-approved test', and alectinib for adjuvant treatment after resection of tumours 4 cm or larger or node-positive (ALINA). Crizotinib is also labelled for ALK-positive anaplastic large cell lymphoma and inflammatory myofibroblastic tumour. Alectinib's label allows selection on tumour tissue or plasma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · ALK is a gene fusion driver in about 4 to 5% of non-small-cell lung cancers that responds to a succession of ALK inhibitor pills. Lorlatinib kept about 60% of patients progression-free at five years, alectinib is approved after surgery, and neladalkib targets compound resistance mutations.
ALK-positive lung cancer is treated first with an ALK tablet, usually alectinib or lorlatinib, instead of chemotherapy or immunotherapy, and responses often last years. After surgery, two years of alectinib is on label for larger or node-positive tumours. If one ALK tablet stops working, others are approved after it.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
An ALK gene rearrangement or fusion by break-apart FISH (15 percent or more of cells with split or isolated 3' signals on the Vysis kit), ALK protein expression by the Ventana D5F3 IHC assay, or a fusion transcript or rearrangement by sequencing of tissue or plasma.
“ALK rearrangements”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| ALK-positive (adjuvant, tumours >= 4 cm or node positive) | Alectinib | Non-small-cell lung cancer | FDA | label |
| ALK-positive | Lorlatinib | Non-small-cell lung cancer | FDA | label |
| ALK-positive or ROS1-positive | Crizotinib | Non-small-cell lung cancer | FDA | label |
| ALK-positive | Brigatinib | Non-small-cell lung cancer | FDA | label |
| ALK-positive, ALK inhibitor-naive | Ensartinib | Non-small-cell lung cancer | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| Vysis ALK Break Apart FISH Probe Kit | Abbott Molecular | Non-Small Cell Lung Cancer (NSCLC) - Tissue | Crizotinib | P110012 (08/26/2011) |
| Vysis ALK Break Apart FISH Probe Kit | Abbott Molecular | Non-Small Cell Lung Cancer (NSCLC) - Tissue | Ensartinib | P110012/S022 (08/05/2025) |
| Ventana ALK (D5F3) CDx Assay | Ventana Medical Systems (Roche) | Non-Small Cell Lung Cancer (NSCLC) - Tissue | Alectinib | P140025/S006 (11/06/2017) |
| Ventana ALK (D5F3) CDx Assay | Ventana Medical Systems (Roche) | Non-Small Cell Lung Cancer (NSCLC) - Tissue | Lorlatinib | P140025/S014 (03/03/2021) |
| FoundationOne CDx | Foundation Medicine | Non-Small Cell Lung Cancer (NSCLC) - Tissue | AlectinibCrizotinibCeritinib | P170019 (11/30/2017) |
| FoundationOne Liquid CDx | Foundation Medicine | Non-Small Cell Lung Cancer (NSCLC) - Plasma | Alectinib | P200006 (10/26/2020) |
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
- NCT05384626 · 2025ALKOVE-1
- NCT03456076 · 2023ALINA
- NCT03052608 · 2020CROWN
- NCT02737501 · 2018ALTA-1L
- NCT02091141 · 2018MyPathway
- NCT02075840 · 2017ALEX
- NCT07491497A Phase 1/2 Study of TRI-611 in ALK-Positive NSCLC
- NCT04774718A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Alectinib in Pediatric Participants With ALK Fusion-Positive Solid or CNS Tumors
- NCT02194738ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials)
- NCT01828112LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib
- NCT01828099LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer
- NCT06765109Neladalkib (NVL-655) for TKI-naive Patients With Advanced ALK-Positive NSCLC
- NCT05765877Neoadjuvant WX-0593 in Resectable ALK-positive or ROS1-positive Non-small Cell Lung Cancer
- NCT06569420Study Of Comparing SAF-189s With Crizotinib In First Line ALK-Positive Advanced and Metastatic NSCLC
- NCT06082635TGRX-326 Chinese Phase III for Advanced Non-small Cell Lung Cancer (NSCLC)
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