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)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of repotrectinib and crizotinib in participants with locally advanced or metastatic TKI-naïve ROS1-positive non-small cell lung cancer (NSCLC).

Official Title
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Randomized, Open-label, Multicenter, Phase 3 Trial 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)

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Repotrectinib
* Drug: Crizotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC Participant has a ROS1 gene rearrangement/fusion as detected by a local test. At least 1 measurable lesion according to RECIST v1.1, as assessed by the investigator. Participants must not be exposed previously with TKIs that demonstrated activities in ROS1-positive NSCLC Up to 1 prior line of systemic treatment for NSCLC is permitted ECOG Performance Status ≤ 2 Exclusion Criteria: Symptomatic brain metastases or symptomatic leptomeningeal involvement. History of previous cancer requiring therapy within the previous 2 years, except for NSCLC under study, squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected. Known tumor targetable co-mutations or rearrangements Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment) Note: Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br> | Drug: Repotrectinib<br>* Specified dose on specified days<br>* Other names: BMS-986472;|
| Active Comparator: Arm B<br> | Drug: Crizotinib<br>* Specified dose on specified days<br>* Other names: Xalkori;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) as per Blinded Independent Central Review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |  | Up to 64 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | Up to 87 months | 
| Overall Response Rate (ORR) as per BICR according to RECIST v1.1 |  | Up to 64 months | 
| ORR as per Investigator according to RECIST v1.1 |  | Up to 64 months | 
| Duration of Response (DOR) as per BICR according to RECIST v1.1 |  | Up to 64 months | 
| DOR as per Investigator according to RECIST v1.1 |  | Up to 64 months | 
| Time to Response (TTR) as per BICR according to RECIST v1.1 |  | Up to 64 months | 
| TTR as per Investigator according to RECIST v1.1 |  | Up to 64 months | 
| PFS as per Investigator according to RECIST v1.1 |  | Up to 64 months | 
| Time to intracranial progressions as per BICR according to RECIST v1.1 |  | Up to 64 months | 
| Number of participants with Adverse Events (AEs), Serious AEs (SAEs), AEs leading to study intervention discontinuation, and drug-related AEs |  | Up to 30 days after last dose | 
| Number of deaths |  | Up to 30 days after last dose | 
| Number of participants without at least a 3-point change in the Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ) total score |  | Up to 30 days after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TKI-naïve, ROS1, NSCLC, ROS1-positive non-small cell lung cancer