# Crizotinib

Source: https://onco.cc/drugs/crizotinib/  
OnCo record `crizotinib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Crizotinib was the first ALK inhibitor, approved four years after ALK fusions were found in lung cancer; it was also the first drug for ROS1 lung cancer and for ALK-positive lymphoma and inflammatory myofibroblastic tumour in children.

## Summary

PROFILE 1007/1014 established it over chemotherapy in ALK+ NSCLC (2011 accelerated, 2013 full); ROS1 approval 2016 (PROFILE 1001, 72% response). Superseded first line by alectinib, brigatinib and lorlatinib (poor CNS penetration). Paediatric approvals for ALK+ ALCL (2021) and IMT (2022). Visual disturbance, oedema, hepatotoxicity.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-08
- Tags: gap-fill
- Brand: Xalkori
- Modality: Small-molecule ALK/ROS1/MET TKI (first generation)
- Mechanism: ATP-competitive inhibitor of ALK, ROS1 and MET kinases.
- Approvals: US 2011: ALK-positive metastatic NSCLC; US 2016: ROS1-positive metastatic NSCLC; US 2021: Relapsed ALK-positive ALCL in patients 1-21 years; US 2022: ALK-positive inflammatory myofibroblastic tumour; EU 2012: Conditional Oct 2012; full approval 2015; England (NICE) 2024: ROS1-positive advanced non-small-cell lung cancer in patients who have not had a ROS1 inhibitor

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Crizotinib
- PROFILE 1014 (NEJM 2014): https://doi.org/10.1056/NEJMoa1408440
- Label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=crizotinib
- NICE TA1021: crizotinib for treating ROS1-positive advanced non-small-cell lung cancer: https://www.nice.org.uk/guidance/ta1021

## Connected records

- biomarkers: [ALK fusion (ALK-positive)](https://onco.cc/biomarkers/alk-fusion/), [ROS1 fusion (ROS1-positive)](https://onco.cc/biomarkers/ros1-fusion/)
- cancers: [ALK-positive non-small-cell lung cancer](https://onco.cc/cancers/alk-positive-nsclc/), [Inflammatory myofibroblastic tumour (IMT)](https://onco.cc/cancers/inflammatory-myofibroblastic-tumour/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [MET exon 14 and MET-amplified non-small-cell lung cancer](https://onco.cc/cancers/met-altered-nsclc/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [ROS1-positive non-small-cell lung cancer](https://onco.cc/cancers/ros1-positive-nsclc/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Sarcomatoid carcinoma of the lung](https://onco.cc/cancers/pulmonary-sarcomatoid-carcinoma/), [Uterine sarcoma](https://onco.cc/cancers/uterine-sarcoma/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ALK](https://onco.cc/targets/alk/), [MET](https://onco.cc/targets/met/), [RON receptor (MST1R)](https://onco.cc/targets/ron/), [ROS1](https://onco.cc/targets/ros1/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- terms: [Gene fusion](https://onco.cc/terms/gene-fusion/), [Lung cancer drugs in England: what NICE has recommended](https://onco.cc/terms/lung-uk-drug-access/), [MET exon 14 skipping mutation](https://onco.cc/terms/met-exon-14-skipping/), [Oncogene addiction](https://onco.cc/terms/oncogene-addiction/)
- trials: [A Phase III Study Comparing Taletrectinib With Standard Therapy in ROS1 Positive Locally Advanced or Metastatic Non-small Cell Lung Cancer Patients](https://onco.cc/trials/nct06564324/), [A Study of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3)](https://onco.cc/trials/nct06140836/), [A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases](https://onco.cc/trials/nct04603807/), [ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials)](https://onco.cc/trials/alchemist/), [ALESIA](https://onco.cc/trials/alesia/), [ALEX](https://onco.cc/trials/alex/), [ALTA-1L](https://onco.cc/trials/alta-1l/), [eXalt3](https://onco.cc/trials/nct02767804/), [GEOMETRY mono-1](https://onco.cc/trials/geometry-mono-1/), [IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma](https://onco.cc/trials/nct05987332/), [J-ALEX](https://onco.cc/trials/j-alex/), [National Lung Matrix Trial](https://onco.cc/trials/national-lung-matrix-trial/), [NCI-MATCH (EAY131)](https://onco.cc/trials/nci-match/), [PAPMET (SWOG S1500)](https://onco.cc/trials/papmet/), [PROFILE 1001 ROS1 expansion cohort](https://onco.cc/trials/profile-1001-ros1/), [PROFILE 1014](https://onco.cc/trials/profile-1014/), [Study Comparing WX-0593 to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients](https://onco.cc/trials/nct04632758/), [Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions](https://onco.cc/trials/nct03947385/), [Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer](https://onco.cc/trials/nct05725200/), [TAPUR (Targeted Agent and Profiling Utilization Registry)](https://onco.cc/trials/tapur/)
- key papers: [Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer](https://onco.cc/key-papers/paper-peters-alex-alectinib-crizotinib-nejm-2017/), [ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer](https://onco.cc/key-papers/paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019/), [Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer](https://onco.cc/key-papers/paper-kwak-crizotinib-alk-nsclc-nejm-2010/), [Crizotinib in ROS1-rearranged non-small-cell lung cancer](https://onco.cc/key-papers/paper-shaw-crizotinib-ros1-nejm-2014/), [First-line crizotinib versus chemotherapy in ALK-positive lung cancer](https://onco.cc/key-papers/paper-solomon-n-engl-j-med/), [First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer](https://onco.cc/key-papers/paper-shaw-crown-lorlatinib-crizotinib-nejm-2020/), [Identification of targetable ALK rearrangements in pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-singhi-alk-rearrangements-pancreatic-jnccn-2017/), [Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer](https://onco.cc/key-papers/paper-soda-eml4-alk-fusion-nature-2007/), [MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression](https://onco.cc/key-papers/paper-awad-met-exon-14-mutations-lung-jco-2016/), [Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer](https://onco.cc/key-papers/paper-gainor-alk-resistance-mutations-cancer-discov-2016/), [PAPMET (SWOG 1500): cabozantinib versus sunitinib for metastatic papillary renal cell carcinoma](https://onco.cc/key-papers/paper-papmet-pal-lancet-2021/), [Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F](https://onco.cc/key-papers/paper-shaw-alk-l1198f-resensitisation-nejm-2016/), [ROS1 rearrangements define a unique molecular class of lung cancers](https://onco.cc/key-papers/paper-bergethon-ros1-rearrangements-lung-jco-2012/)
- drugs: [Capmatinib](https://onco.cc/drugs/capmatinib/)
- institutions: [Children's Hospital of Philadelphia](https://onco.cc/institutions/chop/), [University of Colorado Cancer Center](https://onco.cc/institutions/colorado-cancer-center/)
- roadmaps: [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)

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JSON: https://onco.cc/api/v1/entities/crizotinib.json