{"id":"alk","name":"ALK","symbol":"ALK","route":"/targets/alk/","asOf":"2026-09-04","xrefs":[{"hgnc":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:427","ensembl":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000171094","uniprot":"https://www.uniprot.org/uniprotkb/Q9UM73/entry","alphafold-db":"https://alphafold.ebi.ac.uk/entry/Q9UM73","chembl":"https://www.ebi.ac.uk/chembl/explore/target/CHEMBL4247","open-targets":"https://platform.opentargets.org/target/ENSG00000171094","civic":"https://civicdb.org/genes/238/summary","oncokb":"https://www.oncokb.org/gene/ALK","cosmic":"https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ALK","cbioportal":"https://www.cbioportal.org/results/mutations?cancer_study_list=msk_impact_2017&gene_list=ALK","depmap":"https://depmap.org/portal/gene/ALK?tab=overview","human-protein-atlas":"https://www.proteinatlas.org/ENSG00000171094-ALK","ncbi-gene":"https://www.ncbi.nlm.nih.gov/gene/238","omim":"https://www.omim.org/entry/105590"}],"products":[{"id":"alectinib","name":"Alectinib","status":"approved","modality":"Small-molecule 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Central Nervous System (CNS) Metastases","nct":"NCT04603807","phase":"3","status":"active"},{"id":"anbl1531","name":"COG ANBL1531","nct":"NCT03126916","phase":"3","status":"active"},{"id":"nct06858410","name":"Lorlatinib Compared with Concurrent/ Sequential Chemoradiotherapy in Stage III ALK Positive Lung Adenocarcinoma","nct":"NCT06858410","phase":"3","status":"planned"},{"id":"nct03784014","name":"Molecular Profiling of Advanced Soft-tissue Sarcomas","nct":"NCT03784014","phase":"3","status":"completed"},{"id":"nct06765109","name":"Neladalkib (NVL-655) for TKI-naive Patients With Advanced ALK-Positive NSCLC","nct":"NCT06765109","phase":"3","status":"recruiting"},{"id":"nct04632758","name":"Study Comparing WX-0593 to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients","nct":"NCT04632758","phase":"3"},{"id":"nct06955325","name":"Umbrella Trial of Adjuvant Therapy in Completely Resected High-risk Stage IA-IB NSCLC: Focus on Driver 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Registry)","nct":"NCT02693535","phase":"2","status":"recruiting"},{"id":"mypathway","name":"MyPathway","nct":"NCT02091141","phase":"2","status":"completed"},{"id":"alta","name":"ALTA","nct":"NCT02094573","phase":"2","status":"completed"},{"id":"nct04641754","name":"A Study Evaluates the Safety and Efficacy of WX-0593 in ALK -Positive, or ROS1-positive Non-small Cell Lung Cancer","nct":"NCT04641754","phase":"2"},{"id":"nct05297890","name":"A Study of Lorlatinib in Subjects With ROS1-Positive Non-Small Cell Lung Cancer","nct":"NCT05297890","phase":"2","status":"active"},{"id":"nct04302025","name":"A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)","nct":"NCT04302025","phase":"2","status":"recruiting"},{"id":"nct06780839","name":"Adjuvant Treatment of ALK-positive Non-small Cell Lung Cancer with Ensartinib Guided by MRD","nct":"NCT06780839","phase":"2","status":"planned"},{"id":"nct02568267","name":"Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangeme","nct":"NCT02568267","phase":"2","status":"active"},{"id":"nct05765877","name":"Neoadjuvant WX-0593 in Resectable ALK-positive or ROS1-positive Non-small Cell Lung Cancer","nct":"NCT05765877","phase":"2","status":"recruiting"},{"id":"nct05725200","name":"Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer","nct":"NCT05725200","phase":"2","status":"recruiting"},{"id":"nct04589845","name":"Tumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study","nct":"NCT04589845","phase":"2","status":"active"},{"id":"nct06813079","name":"Using Tumor Models to Determine Treatments","nct":"NCT06813079","phase":"2","status":"recruiting"},{"id":"alkove-1","name":"ALKOVE-1","nct":"NCT05384626","phase":"1/2","status":"positive"},{"id":"nct07491497","name":"A Phase 1/2 Study of TRI-611 in ALK-Positive NSCLC","nct":"NCT07491497","phase":"1/2","status":"recruiting"},{"id":"nct04774718","name":"A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Alectinib in Pediatric Participants With ALK Fusion-Positive Solid or CNS Tumors","nct":"NCT04774718","phase":"1/2","status":"active"},{"id":"nct05987644","name":"Delayed or Upfront Brain RAdiotherapy in Treatment naïve Lung Cancer Patients With Asymptomatic or Minimally Symptomatic Brain Metastases and ALK rEarrangements","nct":"NCT05987644","phase":"1/2","status":"recruiting"},{"id":"nct02650401","name":"Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options","nct":"NCT02650401","phase":"1/2","status":"active"},{"id":"nct03947385","name":"Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions","nct":"NCT03947385","phase":"1/2","status":"recruiting"},{"id":"nct07448116","name":"Study of MCLA-129 in Combination With Ensartinib in Patients With Advanced Solid Tumors.","nct":"NCT07448116","phase":"1/2","status":"recruiting"},{"id":"profile-1001-ros1","name":"PROFILE 1001 ROS1 expansion cohort","nct":"NCT00585195","phase":"1","status":"positive"}],"pathways":["nsclc-signalling","rtk-activation"],"companies":["betta","guardant-health","imagene-ai","inivata","lucence","novartis","nuvalent","pfizer","qilu-pharmaceutical","roche-genentech","takeda","triana-biomedicines","xcovery"],"keyPapers":["paper-wu-alina-adjuvant-alectinib-nejm-2024","paper-philip-kras-wild-type-pancreatic-ccr-2022","paper-zhang-lung-cancer-never-smokers-nat-genet-2021","paper-shaw-crown-lorlatinib-crizotinib-nejm-2020","paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019","paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019","paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019","paper-lindeman-lung-molecular-testing-guideline-jto-2018","paper-peters-alex-alectinib-crizotinib-nejm-2017","paper-alta-jco-2017","paper-ascend-4-lancet-2017","paper-singhi-alk-rearrangements-pancreatic-jnccn-2017","paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017","paper-gainor-alk-resistance-mutations-cancer-discov-2016","paper-shaw-alk-l1198f-resensitisation-nejm-2016","paper-kris-lung-cancer-mutation-consortium-jama-2014","paper-bergethon-ros1-rearrangements-lung-jco-2012","paper-kwak-crizotinib-alk-nsclc-nejm-2010","paper-lemmon-schlessinger-rtk-signalling-cell-2010","paper-soda-eml4-alk-fusion-nature-2007"],"hotspots":[{"label":"F1174L / R1275Q","position":1174,"kind":"activating","drugs":["lorlatinib","crizotinib"]},{"label":"L1196M","position":1196,"kind":"resistance","drugs":["alectinib","brigatinib","ceritinib","lorlatinib","ensartinib"]},{"label":"G1202R","position":1202,"kind":"resistance","frequency":"About 40% of biopsies at progression on second-generation ALK TKIs","drugs":["lorlatinib","neladalkib"]},{"label":"I1171N/T/S and G1269A","position":1171,"kind":"resistance","drugs":["lorlatinib","brigatinib","neladalkib"]}],"openQuestions":[{"id":"alk-fourth-gen","question":"Will fourth-generation ALK inhibitors extend the more than five-year progression-free survival seen with lorlatinib, or is lorlatinib the ceiling for on-target therapy?","stage":"clinical","actor":"industry","source":{"label":"CROWN five-year update, J Clin Oncol 2024","url":"https://doi.org/10.1200/JCO.24.00581"}}],"assays":[{"id":"alk-vysis-fish","name":"Vysis ALK Break Apart FISH Probe Kit","cutoff":"At least 15% of tumour cells with split or isolated 3' signals (at least 50 cells scored)"},{"id":"alk-d5f3","name":"VENTANA ALK (D5F3) CDx Assay","cutoff":"Binary: strong granular cytoplasmic staining in any tumour cells is positive"},{"id":"foundationone-cdx-panel","name":"FoundationOne CDx","cutoff":"Per companion claim: EGFR, ALK, BRAF V600, ERBB2 amplification, KRAS wild-type, BRCA1/2 and HRR genes, PIK3CA, MET exon 14, RET, FGFR2 fusions, IDH1, NTRK fusions; MSI-high; TMB at least 10 mutations per megabase"},{"id":"foundationone-liquid-cdx","name":"FoundationOne Liquid CDx","cutoff":"Per companion claim: EGFR (osimertinib, erlotinib, gefitinib), ALK (alectinib), BRCA1/2 and ATM (olaparib, rucaparib), PIK3CA (alpelisib), FGFR3 (erdafitinib), NTRK and RET; negative plasma results reflex to tissue"}],"resistance":[{"class":"alk-tki","mechanism":"Solvent-front G1202R and compound mutations","category":"on-target"},{"class":"alk-tki","mechanism":"Bypass signalling (MET, EGFR, KRAS)","category":"bypass"}],"licence":"CC BY-NC 4.0, attribution to OnCo (https://onco.cc); commercial use needs a licence"}