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Comparing two medications for advanced ROS1 non-small cell lung cancer

Randomized, Open Label, Multicenter, Phase III Study of Entrectinib Versus Crizotinib in Patients With Locally-Advanced or Metastatic Non-Small Cell Lung Cancer Harboring ROS1 Gene Rearrangements With and Without Central Nervous System Metastases

Phase 3 Interventional Hoffmann-La Roche · NCT04603807

This study is testing which of two medications, entrectinib or crizotinib, works better and is safer for people with advanced ROS1 non-small cell lung cancer.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment220 (estimated)
Ages18 Years and up
SexAll
SponsorHoffmann-La Roche Industry-sponsored
Drugs / interventionsentrectinib, crizotinib, chemotherapy
Locations91 sites (Salvador, Bahia and 90 other locations)
Trial IDNCT04603807 on ClinicalTrials.gov

What this trial studies

This study aims to compare the efficacy and safety of two medications, entrectinib and crizotinib, in patients with advanced or metastatic ROS1 non-small cell lung cancer (NSCLC). Participants will self-administer either drug according to the study protocol until disease progression, unacceptable toxicity, death, or withdrawal occurs. The study will include patients with measurable disease and those with CNS metastases, providing a comprehensive evaluation of both treatments.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced or metastatic ROS1 NSCLC who have not previously received treatment with a ROS1 tyrosine kinase inhibitor.

Not a fit: Patients who have already been treated with a ROS1 tyrosine kinase inhibitor or those with early-stage NSCLC may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could identify a more effective treatment option for patients with advanced ROS1 NSCLC.

How similar studies have performed: Previous studies have shown promising results with ROS1 inhibitors, indicating potential success for this comparative approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Histologically or cytologically-confirmed diagnosis of advanced or recurrent (Stage IIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC that harbors a documented ROS1 gene rearrangement.
* No prior treatment with a ROS1 tyrosine kinase inhibitor, chemotherapy or other systemic therapy for advanced or recurrent (Stage IIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC
* Prior radiotherapy is allowed if more than 14 days have elapsed between the end of treatment and randomization
* Measurable systemic disease according to RECIST v1.1
* Participants with measurable and non-measurable CNS lesions per RECIST v1.1, including leptomeningeal carcinomatosis
* Life expectancy of at least 12 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
* Adequate hematologic, renal, liver functions
* Participants must have recovered from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment
* Ability to swallow entrectinib and crizotinib intact without chewing, crushing, or opening the capsules
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \<1% per year during the treatment period and for up to 5 weeks after the last dose of entrectinib or for at least 90 days after the last dose of crizotinib
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.

Exclusion Criteria:

* Prior treatment with a ROS1 tyrosine kinase inhibitor, chemotherapy or other systemic therapy for advanced or recurrent (Stage IIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC
* NCI-CTCAE v5.0 Grade 3 or higher toxicities due to any prior therapy (excluding alopecia, fatigue, nausea and lack of appetite), which have not shown improvement and are strictly considered to interfere with current study drug
* History of recent (within the past 3 months) symptomatic congestive heart failure or ejection fraction ≤ 50% observed during screening for the study
* History of prolonged corrected QTc interval
* Peripheral sensory neuropathy ≥ Grade 2
* Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis
* Previous malignancy within the past 3 years
* Incomplete recovery from any surgery prior to the start of study treatment
* Active GI disease (e.g., Crohn's disease, ulcerative colitis or short gut syndrome) or other malabsorption syndrome that would reasonably impact drug absorption
* History of prior therapy-induced pneumonitis
* Any condition (in the past 3 months) e.g., myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, stroke, symptomatic bradycardia, or uncontrolled arrhythmias requiring medication
* Known active infections (bacterial, fungal or viral, including human immunodeficiency virus positive)
* History of hypersensitivity to any of the additives in the entrectinib and/or crizotinib drug formulations
* Pregnant or lactating women
* Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS)-related illness
* Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications.

Where this trial is running

Salvador, Bahia and 90 other locations

+41 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Carcinoma, Non-Small-Cell LungROS1 Non-small-cell lung
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.