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)

November 18, 2025 updated by: Bristol-Myers Squibb

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)

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

190

Phase

  • Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1417DTB
        • Local Institution - 0207
      • Buenos Aires, Argentina, 1431
        • Local Institution - 0106
      • Córdoba, Argentina, 5000
        • Local Institution - 0093
    • Buenos Aires
      • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, 1280
        • Local Institution - 0092
      • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1426ANZ
        • Instituto Alexander Fleming
    • Buenos Aires F.D.
      • ABB, Buenos Aires F.D., Argentina, C1199ABB
        • Local Institution - 0091
  • Austria
      • Vienna, Austria, 1210
        • Local Institution - 0041
  • Brazil
      • Rio de Janeiro, Brazil, 22061-080
        • Local Institution - 0098
      • Rio de Janeiro, Brazil, 22250-905
        • Local Institution - 0108
      • São Paulo, Brazil, 01401-002
        • Local Institution - 0032
      • São Paulo, Brazil, 05652-900
        • Local Institution - 0114
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30380-490
        • Local Institution - 0073
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90110-270
        • Local Institution - 0033
      • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
        • Local Institution - 0034
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784400
        • Local Institution - 0029
      • São José do Rio Preto, São Paulo, Brazil, 15090000
        • Local Institution - 0037
      • São Paulo, São Paulo, Brazil, 01308-060
        • Local Institution - 0209
      • São Paulo, São Paulo, Brazil, 01321-001
        • Local Institution - 0147
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Local Institution - 0002
    • Quebec
      • Trois-Rivières, Quebec, Canada, G8Z 3R9
        • Local Institution - 0123
  • Chile
    • Región de Valparaíso
      • Viña del Mar, Región de Valparaíso, Chile, 2520598
        • Local Institution - 0096
    • Santiago Metropolitan
      • Santiago, Santiago Metropolitan, Chile, 7500921
        • Fundación Arturo López Perez (FALP)
  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100142
        • Local Institution - 0168
    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, China, 400042
        • Local Institution - 0185
    • Fujian
      • Xiamen, Fujian, China, 361003
        • Local Institution - 0169
    • Guangdong
      • Guangzhou, Guangdong, China, 510120
        • Local Institution - 0180
    • Guangxi
      • Nanning, Guangxi, China, 530000
        • Local Institution - 0194
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150000
        • Local Institution - 0171
    • Henan
      • Zhengzhou, Henan, China, 450003
        • Local Institution - 0166
    • Hubei
      • Wuhan, Hubei, China, 430079
        • Local Institution - 0181
    • Hunan
      • Changsha, Hunan, China, 410000
        • Local Institution - 0184
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Local Institution - 0193
    • Jiangxi
      • Nanchang, Jiangxi, China, 330006
        • Local Institution - 0202
    • Jilin
      • Changchun, Jilin, China, 130012
        • Local Institution - 0178
    • Shaanxi
      • Xi'an, Shaanxi, China, 710061
        • Local Institution - 0183
    • Shandong
      • Jinan, Shandong, China, 250000
        • Local Institution - 0186
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200030
        • Local Institution - 0164
      • Shanghai, Shanghai Municipality, China, 200032
        • Local Institution - 0179
    • Sichuan
      • Chengdu, Sichuan, China, 610044
        • Local Institution - 0177
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310022
        • Local Institution - 0175
  • France
      • Paris, France, 75014
        • Local Institution - 0056
    • Alsace
      • Strasbourg, Alsace, France, 67091
        • Local Institution - 0059
    • Aquitaine
      • Pessac, Aquitaine, France, 33600
        • Local Institution - 0055
    • Côte-d'Or
      • Dijon, Côte-d'Or, France, 21079
        • Local Institution - 0109
    • Haute-Normandie
      • Rouen, Haute-Normandie, France, 76031
        • Local Institution - 0057
    • Isère
      • La Tronche, Isère, France, 38700
        • Local Institution - 0058
    • Loire-Atlantique
      • Saint-Herblain, Loire-Atlantique, France, 44800
        • Local Institution - 0189
    • Rhône
      • Pierre-Bénite, Rhône, France, 69310
        • Local Institution - 0060
  • Germany
      • Berlin, Germany, 13125
        • Evangelische Lungenklinik Berlin
      • Cologne, Germany, 50937
        • Universitaetsklinikum Koeln
      • Dresden, Germany, 01307
        • Local Institution - 0035
      • Gauting, Germany, 82131
        • Asklepios Klinik Gauting GmbH
      • Immenhausen, Germany, 34376
        • Lungenfachklinik Immenhausen
      • Mainz, Germany, 55131
        • Marienhaus Klinikum Mainz
    • Baden-Wurttemberg
      • Esslingen am Neckar, Baden-Wurttemberg, Germany, 73730
        • Klinikum Esslingen
    • Bavaria
      • Würzburg, Bavaria, Germany, 97074
        • Klinikum Würzburg Mitte
    • Lower Saxony
      • Oldenburg, Lower Saxony, Germany, 26121
        • Local Institution - 0074
  • Greece
    • Achaḯa
      • Pátrai, Achaḯa, Greece, 26504
        • Local Institution - 0154
    • Attikí
      • Athens, Attikí, Greece, 115 27
        • Local Institution - 0153
      • Chaïdári, Attikí, Greece, 124 62
        • Local Institution - 0155
    • Kentrikí Makedonía
      • Thessaloniki, Kentrikí Makedonía, Greece, 540 07
        • "Theagenio" Cancer Hospital of Thessaloniki
  • Hungary
      • Budapest, Hungary, 1121
        • Local Institution - 0135
  • India
    • Gujarat
      • Ahmedabad, Gujarat, India, 380054
        • Local Institution - 0102
      • Ahmedabad, Gujarat, India, 380060
        • Local Institution - 0118
    • Haryana
      • Gurugram, Haryana, India, 122001
        • Local Institution - 0044
    • Karnataka
      • Bengaluru, Karnataka, India, 560017
        • Local Institution - 0082
    • Maharashtra
      • Pune, Maharashtra, India, 411001
        • Local Institution - 0045
      • Pune, Maharashtra, India, 411004
        • Local Institution - 0049
    • National Capital Territory of Delhi
      • New Delhi, National Capital Territory of Delhi, India, 110029
        • Local Institution - 0218
      • New Delhi, National Capital Territory of Delhi, India, 110085
        • Local Institution - 0076
  • Italy
    • Friuli Venezia Giulia
      • Aviano, Friuli Venezia Giulia, Italy, 33081
        • Local Institution - 0151
    • Lombardy
      • Milan, Lombardy, Italy, 20133
        • Local Institution - 0152
      • Monza, Lombardy, Italy, 20900
        • Local Institution - 0149
    • Napoli
      • Naples, Napoli, Italy, 80131
        • Local Institution - 0150
    • Roma
      • Rome, Roma, Italy, 00144
        • Local Institution - 0148
  • Japan
      • Fukuoka, Japan, 811-1395
        • Local Institution - 0195
      • Osaka, Japan, 534-0021
        • Local Institution - 0160
      • Osaka, Japan, 541-8567
        • Local Institution - 0167
      • Tokyo, Japan, 164-8541
        • Tokyo Metropolitan Police Hospital
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan, 466-8560
        • Local Institution - 0190
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
        • Local Institution - 0132
    • Ehime
      • Matsuyama, Ehime, Japan, 791-0280
        • Local Institution - 0174
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8648
        • Local Institution - 0163
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 2418515
        • Local Institution - 0173
    • Miyagi
      • Sendai, Miyagi, Japan, 9800873
        • Sendai Kosei Hospital
    • Tokyo
      • Bunkyo Ku, Tokyo, Japan, 113-8677
        • Tokyo Metropolitan Komagome Hospital
    • Tottori
      • Yonago, Tottori, Japan, 683-8504
        • Local Institution - 0159
  • Netherlands
    • North Holland
      • Amsterdam, North Holland, Netherlands, 1081 HV
        • Local Institution - 0216
  • Poland
    • Lublin Voivodeship
      • Lublin, Lublin Voivodeship, Poland, 20-609
        • Local Institution - 0187
    • Warmian-Masurian Voivodeship
      • Olsztyn, Warmian-Masurian Voivodeship, Poland, 10-357
        • Local Institution - 0196
  • Romania
      • Cluj-Napoca, Romania, 400015
        • Local Institution - 0122
      • Iași, Romania, 700106
        • Local Institution - 0067
    • București
      • Bucharest, București, Romania, 022328
        • Local Institution - 0066
      • Bucharest, București, Romania, 013812
        • Local Institution - 0030
    • Dolj
      • Craiova, Dolj, Romania, 200746
        • Local Institution - 0031
  • South Korea
    • Chungcheongbuk-do [Chungbuk]
      • Cheongju-si, Chungcheongbuk-do [Chungbuk], South Korea, 28644
        • Local Institution - 0062
    • Kyǒnggi-do
      • Seongnam, Kyǒnggi-do, South Korea, 13620
        • Seoul National University Bundang Hospital
    • Seoul-teukbyeolsi [Seoul]
      • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 05505
        • Asan Medical Center
      • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 06351
        • Local Institution - 0063
  • Spain
      • Málaga, Spain, 29011
        • Local Institution - 0142
      • Seville, Spain, 41013
        • Local Institution - 0144
      • Valencia, Spain, 46026
        • Local Institution - 0143
    • A Coruña [La Coruña]
      • A Coruña, A Coruña [La Coruña], Spain, 15006
        • Local Institution - 0141
      • Santiago de Compostela, A Coruña [La Coruña], Spain, 15706
        • Local Institution - 0138
    • Barcelona [Barcelona]
      • Barcelona, Barcelona [Barcelona], Spain, 08035
        • Local Institution - 0140
    • Madrid, Comunidad de
      • Madrid, Madrid, Comunidad de, Spain, 28041
        • Local Institution - 0137
      • Majadahonda, Madrid, Comunidad de, Spain, 28222
        • Local Institution - 0139
  • Switzerland
    • Canton of Aargau
      • Baden, Canton of Aargau, Switzerland, 5404
        • Kantonspital Baden
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 01140
        • Local Institution - 0088
      • Ankara, Turkey (Türkiye), 06010
        • Local Institution - 0084
      • Istanbul, Turkey (Türkiye), 34214
        • Local Institution - 0087
      • Istanbul, Turkey (Türkiye), 34440
        • T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi
      • Istanbul, Turkey (Türkiye), 34899
        • Local Institution - 0083
      • Sakarya, Turkey (Türkiye)
        • Local Institution - 0085
    • Ankara
      • Yenimahalle, Ankara, Turkey (Türkiye), 06200
        • Local Institution - 0086
  • United States
    • Iowa
      • Des Moines, Iowa, United States, 50309
        • Local Institution - 0221
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Local Institution - 0075
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 0201
    • New York
      • Mineola, New York, United States, 11501
        • Local Institution - 0210
      • New York, New York, United States, 10016
        • Local Institution - 0134
    • Washington
      • Tacoma, Washington, United States, 98405
        • Local Institution - 0214

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
Drug: Repotrectinib
Specified dose on specified days
Other Names:
  • BMS-986472
Active Comparator: Arm B
Drug: Crizotinib
Specified dose on specified days
Other Names:
  • Xalkori

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-free Survival (PFS) as per Blinded Independent Central Review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame: Up to approximately 41 months
Up to approximately 41 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of participants with Adverse Events (AEs), Serious AEs (SAEs), AEs leading to study intervention discontinuation, and drug-related AEs
Time Frame: Up to 30 days after last dose
Up to 30 days after last dose
Number of deaths
Time Frame: Up to 30 days after last dose
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
Time Frame: Up to 30 days after last dose
Up to 30 days after last dose
Overall Survival (OS)
Time Frame: Up to approximately 41 months
Up to approximately 41 months
Overall Response Rate (ORR) as per BICR according to RECIST v1.1
Time Frame: Up to approximately 41 months
Up to approximately 41 months
ORR as per Investigator according to RECIST v1.1
Time Frame: Up to approximately 41 months
Up to approximately 41 months
Duration of Response (DOR) as per BICR according to RECIST v1.1
Time Frame: Up to approximately 41 months
Up to approximately 41 months
DOR as per Investigator according to RECIST v1.1
Time Frame: Up to approximately 41 months
Up to approximately 41 months
Time to Response (TTR) as per BICR according to RECIST v1.1
Time Frame: Up to approximately 41 months
Up to approximately 41 months
TTR as per Investigator according to RECIST v1.1
Time Frame: Up to approximately 41 months
Up to approximately 41 months
PFS as per Investigator according to RECIST v1.1
Time Frame: Up to approximately 41 months
Up to approximately 41 months
Time to intracranial progressions as per BICR according to RECIST v1.1
Time Frame: Up to approximately 41 months
Up to approximately 41 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Collaborators

Zai Lab (Shanghai) Co., Ltd.

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 21, 2023

Primary Completion (Estimated)

March 13, 2026

Study Completion (Estimated)

March 15, 2027

Study Registration Dates

First Submitted

November 15, 2023

First Submitted That Met QC Criteria

November 15, 2023

First Posted (Actual)

November 20, 2023

Study Record Updates

Last Update Posted (Actual)

November 21, 2025

Last Update Submitted That Met QC Criteria

November 18, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA127-1030
  • U1111-1292-0487 (Registry Identifier: WHO)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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