# Lorlatinib

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

## TL;DR

An ALK inhibitor with the longest disease control ever recorded for a targeted lung cancer pill: 60% progression-free at five years.

## Summary

Lorlatinib is a macrocyclic third-generation ALK and ROS1 inhibitor designed to cover resistance mutations including G1202R and to cross the blood-brain barrier, taken as 100 mg once daily. In CROWN it achieved a 5-year progression-free survival of 60% versus 8% for crizotinib, with near-complete protection against brain progression. It was approved in 2018 after prior ALK inhibitors and in 2021 for first-line ALK-positive NSCLC. Its distinctive toxicities are metabolic and neurological: raised cholesterol and triglycerides, weight gain, oedema, neuropathy and cognitive or mood effects, which need active management. Its position against alectinib and newer agents such as neladalkib remains open. For a newcomer: the ALK pill with the most durable results, balanced against side effects that touch thinking and mood.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-04
- Brand: Lorbrena
- Modality: Small-molecule kinase inhibitor (ALK/ROS1)
- Mechanism: Macrocyclic third-generation ALK/ROS1 TKI covering G1202R.
- Approvals: US 2018: ALK+ NSCLC after prior ALK TKI; US 2021: First-line ALK+ NSCLC; England (NICE) 2020: ALK-positive advanced non-small-cell lung cancer progressing after alectinib or ceritinib as the first ALK inhibitor, or after crizotinib and at least one other ALK inhibitor; England (NICE) 2025: ALK-positive advanced non-small-cell lung cancer not previously treated with an ALK inhibitor
- Dosing: Oral; 100 mg once daily

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Lorlatinib
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Lorlatinib
- NICE TA628: lorlatinib for previously treated ALK-positive advanced non-small-cell lung cancer: https://www.nice.org.uk/guidance/ta628
- NICE TA1103: lorlatinib for ALK-positive advanced non-small-cell lung cancer not treated with an ALK inhibitor: https://www.nice.org.uk/guidance/ta1103

## Connected records

- biomarkers: [ALK fusion (ALK-positive)](https://onco.cc/biomarkers/alk-fusion/)
- cancers: [ALK-positive non-small-cell lung cancer](https://onco.cc/cancers/alk-positive-nsclc/), [Brain metastases (secondary brain tumours)](https://onco.cc/cancers/secondary-brain-tumours/), [High-risk neuroblastoma](https://onco.cc/cancers/neuroblastoma-high-risk/), [Inflammatory myofibroblastic tumour (IMT)](https://onco.cc/cancers/inflammatory-myofibroblastic-tumour/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Neuroblastoma (paediatric)](https://onco.cc/cancers/neuroblastoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Paediatric high-grade glioma (excluding diffuse midline glioma)](https://onco.cc/cancers/paediatric-high-grade-glioma/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ALK](https://onco.cc/targets/alk/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- trials: [A Study of Lorlatinib in Subjects With ROS1-Positive Non-Small Cell Lung Cancer](https://onco.cc/trials/nct05297890/), [COG ANBL1531](https://onco.cc/trials/anbl1531/), [CROWN](https://onco.cc/trials/crown/), [Lorlatinib Compared with Concurrent/ Sequential Chemoradiotherapy in Stage III ALK Positive Lung Adenocarcinoma](https://onco.cc/trials/nct06858410/)
- drugs: [Neladalkib](https://onco.cc/drugs/neladalkib/)
- pairings: [Sequence: targeted therapy before immunotherapy in driver-positive NSCLC](https://onco.cc/pairings/targeted-before-io-nsclc/)
- terms: [Graded Prognostic Assessment (GPA) for brain metastases](https://onco.cc/terms/graded-prognostic-assessment/), [Kinase](https://onco.cc/terms/kinase/), [Lung cancer drugs in England: what NICE has recommended](https://onco.cc/terms/lung-uk-drug-access/), [MYCN amplification](https://onco.cc/terms/mycn-amplification/), [Segmental chromosomal aberrations and ploidy (neuroblastoma)](https://onco.cc/terms/segmental-chromosomal-aberrations/)
- key papers: [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/), [First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer](https://onco.cc/key-papers/paper-shaw-crown-lorlatinib-crizotinib-nejm-2020/), [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/), [Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F](https://onco.cc/key-papers/paper-shaw-alk-l1198f-resensitisation-nejm-2016/)
- pathways: [Drug efflux pumps (ABC transporters)](https://onco.cc/pathways/drug-efflux-pumps/), [Non-small cell lung cancer (KEGG map)](https://onco.cc/pathways/nsclc-signalling/), [Organ tropism: seed and soil](https://onco.cc/pathways/organ-tropism-seed-soil/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/), [Resistance routes: how a blocked pathway comes back](https://onco.cc/pathways/resistance-routes-map/), [The blood-brain barrier & brain metastasis](https://onco.cc/pathways/blood-brain-barrier-metastasis/)
- people: [Benjamin Solomon](https://onco.cc/people/solomon-benjamin/), [D. Ross Camidge](https://onco.cc/people/ross-camidge/), [Dong-Wan Kim](https://onco.cc/people/kim-dong-wan/), [Justin F. Gainor](https://onco.cc/people/justin-gainor/), [Myung-Ju Ahn](https://onco.cc/people/ahn-myung-ju/), [Yael P. Mossé](https://onco.cc/people/yael-mosse/)
- ideas: [Brain metastases included by default in every solid-tumour trial](https://onco.cc/ideas/idea-tr1-brain-mets-default-included/), [Develop drugs in children first when the target is a children's target](https://onco.cc/ideas/idea-bio2-paediatric-first-development/), [Prevention trials aimed only at brain metastasis](https://onco.cc/ideas/idea-bio2-brain-met-prevention-trials/), [Switch drugs at maximum response, not at relapse](https://onco.cc/ideas/idea-bio1-first-strike-second-strike/)
- institutions: [Children's Hospital of Philadelphia](https://onco.cc/institutions/chop/), [Shanghai Chest Hospital](https://onco.cc/institutions/shanghai-chest-hospital/), [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/lorlatinib.json