# CROWN

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

## TL;DR

The trial with the longest disease control ever seen for a targeted lung cancer pill: most patients still progression-free at five years.

## Summary

296 patients. At 5 years, PFS was 60% with lorlatinib versus 8% with crizotinib (HR 0.19); median PFS not reached after >60 months of follow-up. Intracranial progression was nearly abolished (5-year cumulative incidence ~8% in patients without baseline brain metastases). Neurocognitive, mood, weight, and lipid effects require management.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-06
- Registry id: NCT03052608
- Phase: 3
- Setting: First-line ALK-positive advanced NSCLC: lorlatinib vs crizotinib
- Sponsor: Pfizer
- Enrolled: 296
- Result: 5-year PFS 60% vs 8%, HR 0.19 (JCO 2024).
- Outcomes: Progression-free survival at 5 years (BICR): Lorlatinib 60% vs Crizotinib 8%, HR 0.19; Intracranial progression at 5 years: Lorlatinib 8% vs Crizotinib 40%
- Replication: Single pivotal trial versus crizotinib; consistent with ALEX (alectinib) and eXalt3 (ensartinib) for the class, with lorlatinib showing the longest PFS.

## Sources

- ClinicalTrials.gov NCT03052608: https://clinicaltrials.gov/study/NCT03052608

## Connected records

- 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/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ALK](https://onco.cc/targets/alk/)
- drugs: [Lorlatinib](https://onco.cc/drugs/lorlatinib/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- people: [Benjamin Solomon](https://onco.cc/people/solomon-benjamin/), [D. Ross Camidge](https://onco.cc/people/ross-camidge/), [Myung-Ju Ahn](https://onco.cc/people/ahn-myung-ju/)
- key papers: [Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study](https://onco.cc/key-papers/paper-crown-lancet-respir-med-2023-update/), [First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer](https://onco.cc/key-papers/paper-shaw-crown-lorlatinib-crizotinib-nejm-2020/)
- pairings: [Sequence: targeted therapy before immunotherapy in driver-positive NSCLC](https://onco.cc/pairings/targeted-before-io-nsclc/)
- trials: [ASCEND-4](https://onco.cc/trials/nct01828099/), [eXalt3](https://onco.cc/trials/nct02767804/), [PROFILE 1014](https://onco.cc/trials/profile-1014/)

---
JSON: https://onco.cc/api/v1/entities/crown.json