Clinical trial NCT06140836: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: TKI-naïve
ROS1
NSCLC
ROS1-positive non-small cell lung cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Zai Lab (Shanghai) Co., Ltd.
First posted: 2023-11-20
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS) as per Blinded Independent Central Review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Up to approximately 41 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 41 months
measure: Overall Response Rate (ORR) as per BICR according to RECIST v1.1
timeFrame: Up to approximately 41 months
measure: ORR as per Investigator according to RECIST v1.1
timeFrame: Up to approximately 41 months
measure: Duration of Response (DOR) as per BICR according to RECIST v1.1
timeFrame: Up to approximately 41 months
measure: DOR as per Investigator according to RECIST v1.1
timeFrame: Up to approximately 41 months
measure: Time to Response (TTR) as per BICR according to RECIST v1.1
timeFrame: Up to approximately 41 months
measure: TTR as per Investigator according to RECIST v1.1
timeFrame: Up to approximately 41 months
measure: PFS as per Investigator according to RECIST v1.1
timeFrame: Up to approximately 41 months
measure: Time to intracranial progressions as per BICR according to RECIST v1.1
timeFrame: Up to approximately 41 months
measure: Number of participants with Adverse Events (AEs), Serious AEs (SAEs), AEs leading to study intervention discontinuation, and drug-related AEs
timeFrame: Up to 30 days after last dose
measure: Number of deaths
timeFrame: Up to 30 days after last dose
measure: Number of participants without at least a 3-point change in the Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ) total score
timeFrame: Up to 30 days after last dose
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Local Institution - 0136
state: Georgia
city: Des Moines
country: United States
facility: Local Institution - 0221
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Brooklyn
country: United States
facility: Local Institution - 0217
state: New York
city: Mineola
country: United States
facility: Perlmutter Cancer Center at NYU Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Tacoma
country: United States
facility: Local Institution - 0214
state: Washington
city: Milwaukee
country: United States
facility: Local Institution - 0061
state: Wisconsin
city: Ciudad autónoma de Buenos Aires
country: Argentina
facility: Hospital Británico de Buenos Aires
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Instituto Alexander Fleming
state: Buenos Aires
city: ABB
country: Argentina
facility: Hospital Italiano de Buenos Aires
state: Ciudad Autónoma De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Centro de Educación Médica e Investigaciones clínicas "Dr. Norberto Quirno" (CEMIC)
city: Buenos Aires
country: Argentina
facility: Instituto de Oncología Angel H. Roffo
city: Córdoba
country: Argentina
facility: Instituto Oncológico de Córdoba
city: Wien
country: Austria
facility: Klinik Floridsdorf
city: Belo Horizonte
country: Brazil
facility: Hospital Luxemburgo
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Fundação Pio XII - Hospital de Câncer de Barretos
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Sírio Libanês
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Paulistano
state: São Paulo
city: São José do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Hospital São Lucas de Copacabana
city: Rio de Janeiro
country: Brazil
facility: Centro de Tratamento de Tumores Botafogo para Oncoclinicas Rio de Janeiro SA
city: São Paulo
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino (IDOR)
city: São Paulo
country: Brazil
facility: Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
city: Toronto
country: Canada
facility: Local Institution - 0002
state: Ontario
city: Trois-Rivières
country: Canada
facility: Local Institution - 0123
state: Quebec
city: Santiago
country: Chile
facility: Fundacion Arturo Lopez Perez (FALP)
state: Región Metropolitana De Santiago
city: Viña del Mar
country: Chile
facility: Oncocentro Apys
state: Valparaíso
city: Beijing
country: China
facility: Beijing Cancer hospital
state: Beijing
city: Chongqing
country: China
facility: Army Medical Center of PLA
state: Chongqing
city: Fuzhou
country: China
facility: Local Institution - 0192
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Harbin
country: China
facility: Affiliated Cancer Hospital of Harbin Medical University
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan Shi
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Wuhan
country: China
facility: Local Institution - 0203
state: Hubei
city: Changsha
country: China
facility: Hunan Province People'S Hospital
state: Hunan
city: Changsha
country: China
facility: Local Institution - 0165
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital Of Chinese Medicine
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Linyi
country: China
facility: Local Institution - 0205
state: Shandong
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Chengdu
country: China
facility: Local Institution - 0170
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Kunming
country: China
facility: Local Institution - 0204
state: Yunnan
city: Hangzhou
country: China
facility: Local Institution - 0206
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil (NHC)
state: Alsace
city: Pessac
country: France
facility: CHU Bordeaux Haut-Leveque
state: Aquitaine
city: Dijon
country: France
facility: Centre Georges François Leclerc
state: Côte-d'Or
city: Rouen
country: France
facility: CHU Charles Nicolle
state: Haute-Normandie
city: La Tronche
country: France
facility: Chu Grenoble Alpes
state: Isère
city: Saint-Herblain
country: France
facility: Hôpital Nord Guillaume-et-René-Laennec / CHU de Nantes
state: Loire-Atlantique
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
state: Rhône
city: Paris
country: France
facility: Hopitaux Universitaires Paris Centre-Hopital Cochin
city: Esslingen
country: Germany
facility: Klinikum Esslingen
state: Baden-Württemberg
city: Wuerzburg
country: Germany
facility: Klinikum Würzburg Mitte
state: Bayern
city: Oldenburg
country: Germany
facility: Pius Hospital Oldenburg
state: Niedersachsen
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden
city: Gauting
country: Germany
facility: Asklepios Klinik Gauting GmbH
city: Immenhausen
country: Germany
facility: Lungenfachklinik Immenhausen
city: Köln
country: Germany
facility: Universitaetsklinikum Koeln
city: Mainz
country: Germany
facility: Marienhaus Klinikum Mainz
city: Patras
country: Greece
facility: University Hospital of Patras
state: Achaḯa
city: Athens
country: Greece
facility: Thoracic General Hospital of Athens "I Sotiria"
state: Attikí
city: Chaidari
country: Greece
facility: Attikon General University Hospital
state: Attikí
city: Thessaloniki
country: Greece
facility: "Theagenio" Cancer Hospital of Thessaloniki
state: Kentrikí Makedonía
city: Budapest
country: Hungary
facility: Országos Korányi Pulmonológiai Intézet
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
state: Delhi
city: New Delhi
country: India
facility: Rajiv Gandhi Cancer Institute And Research Centre
state: Delhi
city: Ahmedabad
country: India
facility: Hemato Oncology Clinic
state: Gujarat
city: Ahmedabad
country: India
facility: HCG Aastha Cancer Centre
state: Gujarat
city: Gurgaon
country: India
facility: Local Institution - 0117
state: Haryana
city: Gurugram
country: India
facility: Artemis hospital
state: Haryana
city: Bengaluru
country: India
facility: Manipal Hospitals
state: Karnataka
city: Thiruvananthapuram
country: India
facility: Local Institution - 0219
state: Kerala
city: Mumbai
country: India
facility: Local Institution - 0065
state: Maharashtra
city: Mumbai
country: India
facility: Local Institution - 0048
state: Maharashtra
city: Pune
country: India
facility: Grant Medical Foundation - Ruby Hall Clinic
state: Maharashtra
city: Pune
country: India
facility: Sahyadri Super Speciality Hospital
state: Maharashtra
city: Hyderabad
country: India
facility: Local Institution - 0220
state: Telangana
city: Aviano
country: Italy
facility: Cro-Irccs
state: Friuli-Venezia Giulia
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: Lombardia
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
state: Lombardia
city: Naples
country: Italy
facility: A.O.R.N. Ospedale dei Colli - Monaldi V.
state: Napoli
city: Rome
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
state: Roma
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Yokohama
country: Japan
facility: Kanagawa cancer center
state: Kanagawa
city: Sendai
country: Japan
facility: Sendai Kosei Hospital
state: Miyagi
city: Bunkyo ku
country: Japan
facility: Tokyo Metropolitan Komagome Hospital
state: Tokyo
city: Yonago
country: Japan
facility: Tottori University Hospital
state: Tottori
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Police Hospital
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbuk-do [Chungbuk]
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Kyǒnggi-do
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul-teukbyeolsi [Seoul]
city: Kuala Lumpur
country: Malaysia
facility: Local Institution - 0223
state: Wilayah Persekutuan Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: Local Institution - 0237
state: Wilayah Persekutuan Kuala Lumpur
city: Lembah Pantai
country: Malaysia
facility: Local Institution - 0222
state: Wilayah Persekutuan Kuala Lumpur
city: Lembah Pantai
country: Malaysia
facility: Local Institution - 0226
state: Wilayah Persekutuan Kuala Lumpur
city: Putrajaya
country: Malaysia
facility: Local Institution - 0224
state: Wilayah Persekutuan Kuala Lumpur
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, locatie VUmc
state: Noord-Holland
city: Groningen
country: Netherlands
facility: Local Institution - 0215
city: Lublin
country: Poland
facility: Instytut Genetyki i Immunologii GENIM
state: Lubelskie
city: Olsztyn
country: Poland
facility: Warmińsko - Mazurskie Centrum Chorób Płuc w Olsztynie
state: Warmińsko-mazurskie
city: Bucharest
country: Romania
facility: SC Memorial Healthcare International SRL
state: București
city: Bucharest
country: Romania
facility: Institutul Oncologic Bucuresti
state: București
city: Craiova
country: Romania
facility: Centrul de Oncologie "Sfântul Nectarie"
state: Dolj
city: Cluj
country: Romania
facility: Institutul Oncologic Cluj
city: Iași
country: Romania
facility: S.C. Centrul de Oncologie Euroclinic S.R.L.
city: A Coruña
country: Spain
facility: CHUAC-Hospital Teresa Herrera
state: A Coruña [La Coruña]
city: Santiago de Compostela
country: Spain
facility: CHUS - Hospital Clinico Universitario
state: A Coruña [La Coruña]
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [Barcelona]
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Madrid, Comunidad De
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid, Comunidad De
city: Málaga
country: Spain
facility: H.R.U Málaga - Hospital General
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: València
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Baden
country: Switzerland
facility: Kantonspital Baden
state: Aargau
city: Yenimahalle
country: Turkey
facility: Ankara Bilkent Şehir Hastanesi
state: Ankara
city: Adana
country: Turkey
facility: Adana Medical Park Seyhan Hastanesi
city: Ankara
country: Turkey
facility: Sbü Gülhane Eğitim Ve Araştirma Hastanesi
city: Istanbul
country: Turkey
facility: Medipol Mega Universite Hastanesi
city: Istanbul
country: Turkey
facility: T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi
city: Istanbul
country: Turkey
facility: VM Medical Park Pendik Hospital
city: Sakarya
country: Turkey
facility: Sakarya Training and Research Hospital
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: