# PROFILE 1001 ROS1 expansion cohort

Source: https://onco.cc/trials/profile-1001-ros1/  
OnCo record `profile-1001-ros1` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Fifty patients in an expansion cohort defined ROS1 as the second treatable fusion in lung cancer and put crizotinib on the label for it.

## Summary

ROS1 rearrangements occur in about 1 to 2 percent of non-small-cell lung cancers, most often in younger never-smokers with adenocarcinoma. Crizotinib inhibits ALK, ROS1 and MET, and the kinase domains of ALK and ROS1 are close enough that the same molecule fits both. Fifty patients with ROS1-positive advanced disease were enrolled in an expansion cohort of the phase 1 crizotinib study and treated at the standard 250 mg twice daily.

The objective response rate was 72 percent (95 percent confidence interval 58 to 84) with three complete and 33 partial responses; median duration of response was 17.6 months and median progression-free survival 19.2 months, with half the patients still in follow-up for progression at the report. Seven ROS1 fusion partners were identified among 30 tumours tested, five known and two new, and the partner did not predict response. Safety matched the ALK experience.

The FDA added ROS1-positive metastatic non-small-cell lung cancer to the crizotinib label in 2016 on this cohort. NICE TA1021 (4 December 2024) recommends crizotinib for ROS1-positive advanced disease in England. Crizotinib has since been overtaken by entrectinib and repotrectinib, which cross into the brain and, in repotrectinib's case, cover the ROS1 G2032R solvent-front mutation.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-25
- Also known as: Crizotinib in ROS1-rearranged NSCLC
- Registry id: NCT00585195
- Phase: 1
- Setting: Advanced ROS1-rearranged non-small-cell lung cancer: crizotinib 250 mg twice daily in an expansion cohort of the phase 1 study, with objective response as the endpoint
- Sponsor: Pfizer
- Enrolled: 50
- Result: Objective response 72 percent (36 of 50); median duration of response 17.6 months; median progression-free survival 19.2 months.
- Outcomes: Objective response rate: Crizotinib 72%; Progression-free survival: Crizotinib 19.2 months
- Replication: Entrectinib (integrated ALKA-372-001, STARTRK-1 and STARTRK-2 analysis) and repotrectinib (TRIDENT-1) reproduced and exceeded the activity, with intracranial responses crizotinib does not produce.

## Sources

- ClinicalTrials.gov NCT00585195: https://clinicaltrials.gov/study/NCT00585195
- Crizotinib in ROS1-rearranged NSCLC (New England Journal of Medicine 2014): https://doi.org/10.1056/NEJMoa1406766
- NICE TA1021: crizotinib for treating ROS1-positive advanced non-small-cell lung cancer: https://www.nice.org.uk/guidance/ta1021

## Connected records

- cancers: [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [ROS1-positive non-small-cell lung cancer](https://onco.cc/cancers/ros1-positive-nsclc/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ROS1](https://onco.cc/targets/ros1/)
- drugs: [Crizotinib](https://onco.cc/drugs/crizotinib/), [Entrectinib](https://onco.cc/drugs/entrectinib/), [Repotrectinib](https://onco.cc/drugs/repotrectinib/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- terms: [Gene fusion](https://onco.cc/terms/gene-fusion/), [Oncogene addiction](https://onco.cc/terms/oncogene-addiction/), [Tyrosine kinase inhibitor (TKI)](https://onco.cc/terms/tki-term/)
- trials: [A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements](https://onco.cc/trials/nct03093116/), [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](https://onco.cc/trials/nct02568267/)

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