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)

Carcinoma, Non-Small-Cell Lung Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06140836
• Other study ID #: CA127-1030
• Secondary ID: U1111-1292-0487
• Status: Recruiting
• Phase: Phase 3
• Start date: December 21, 2023
• Est. completion date: January 27, 2031

Study information

• Verified date: June 2024
• Source: Bristol-Myers Squibb
• Contact: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
• Phone: 855-907-3286
• Email: Clinical.Trials[@]bms.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 230
• Est. completion date: January 27, 2031
• Est. primary completion date: February 26, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• Repotrectinib
Specified dose on specified days
• Crizotinib
Specified dose on specified days

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	ABB	Ciudad Autónoma De Buenos Aires
Argentina	Centro de Educación Médica e Investigaciones clínicas "Dr. Norberto Quirno" (CEMIC)	Buenos Aires
Argentina	Local Institution - 0207	Buenos Aires
Argentina	Hospital Británico de Buenos Aires	Ciudad autónoma de Buenos Aires	Buenos Aires
Argentina	Instituto Alexander Fleming	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	Instituto Oncológico de Córdoba	Córdoba
Austria	Klinik Floridsdorf	Wien
Brazil	Fundação Pio XII - Hospital de Câncer de Barretos	Barretos	São Paulo
Brazil	Hospital Luxemburgo	Belo Horizonte	Minas Gerais
Brazil	Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital São Lucas da PUCRS	Porto Alegre	Rio Grande Do Sul
Brazil	Grupo Oncoclinicas Botafogo	Rio de Janeiro
Brazil	Hospital São Lucas de Copacabana	Rio de Janeiro
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José do Rio Preto	São Paulo
Brazil	Hospital Paulistano	Sao Paulo	São Paulo
Brazil	Local Institution - 0209	Sao Paulo	São Paulo
Brazil	Instituto D'Or de Pesquisa e Ensino (IDOR)	São Paulo
Brazil	Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein	São Paulo
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Centre integre universitaire de sante et de services sociaux de la Mauricie-et-du-centre-du-quebec	Trois-Rivières	Quebec
Chile	FALP	Santiago	Región Metropolitana De Santiago
Chile	Oncocentro Apys	Viña del Mar	Valparaíso
China	Beijing Cancer hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	Hunan Province People'S Hospital	Changsha	Hunan
China	Local Institution - 0165	Changsha	Hunan
China	Local Institution - 0170	Chengdu	Sichuan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Army Medical Center of PLA	Chongqing	Chongqing
China	Local Institution - 0192	Fuzhou	Fujian
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Local Institution - 0206	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Local Institution - 0171	Harbin	Heilongjiang
China	Shandong Cancer Hospital	Jinan	Shandong
China	Local Institution - 0204	Kunming	Yunnan
China	Local Institution - 0205	Linyi	Shandong
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Province Hospital Of Chinese Medicine	Nanjing	Jiangsu
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Local Institution - 0179	Shanghai	Shanghai
China	Shanghai Chest Hospital	Shanghai	Shanghai
China	Local Institution - 0203	Wuhan	Hubei
China	Hubei Cancer Hospital	Wuhan Shi	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	The First Affiliated hospital of Xiamen University	Xiamen	Fujian
China	Henan Cancer Hospital	Zhengzhou	Henan
France	Centre Georges François Leclerc	Dijon	Côte-d'Or
France	Chu Grenoble Alpes	La Tronche	Isère
France	Hopitaux Universitaires Paris Centre-Hopital Cochin	Paris
France	CHU Bordeaux Haut-Leveque	Pessac	Aquitaine
France	Centre Hospitalier Lyon Sud	Pierre-Bénite	Rhône
France	Hopital Charles Nicolle C H U Rouen	Rouen	Haute-Normandie
France	Hôpital Nord Guillaume-et-René-Laennec / CHU de Nantes	Saint-Herblain	Loire-Atlantique
France	Nouvel Hôpital Civil (NHC)	Strasbourg	Alsace
Germany	Evangelische Lungenklinik Berlin	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Klinikum Esslingen	Esslingen	Baden-Württemberg
Germany	Asklepios Klinik Gauting GmbH	Gauting
Germany	Lungenfachklinik Immenhausen	Immenhausen
Germany	Universitaetsklinikum Koeln	Köln
Germany	Marienhaus Klinikum Mainz	Mainz
Germany	Pius Hospital Oldenburg	Oldenburg	Niedersachsen
Germany	Klinikum Würzburg Mitte	Wuerzburg	Bayern
Greece	Thoracic General Hospital of Athens "I Sotiria"	Athens	Attikí
Greece	Attikon General University Hospital	Chaidari	Attikí
Greece	University Hospital of Patras	Patras	Acha?a
Greece	Theagenio Hospital	Thessaloniki	Kentrikí Makedonía
Hungary	Local Institution - 0135	Budapest
India	Local Institution - 0102	Ahmedabad	Gujarat
India	Local Institution - 0118	Ahmedabad	Gujarat
India	Local Institution - 0082	Bengaluru	Karnataka
India	Local Institution - 0117	Gurgaon	Haryana
India	Local Institution - 0044	Gurugram	Haryana
India	Local Institution - 0220	Hyderabad	Telangana
India	Local Institution - 0048	Mumbai	Maharashtra
India	Local Institution - 0065	Mumbai	Maharashtra
India	Local Institution - 0076	New Delhi	Delhi
India	Local Institution - 0218	New Delhi	Delhi
India	Local Institution - 0045	Pune	Maharashtra
India	Local Institution - 0049	Pune	Maharashtra
India	Local Institution - 0219	Thiruvananthapuram	Kerala
Italy	Cro-Irccs	Aviano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milan	Lombardia
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza	Lombardia
Italy	A.O.R.N. Ospedale dei Colli - Monaldi V.	Naples	Napoli
Italy	Istituto Nazionale Tumori Regina Elena	Rome	Roma
Japan	Local Institution - 0198	Bunkyo ku	Tokyo
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama	Ehime
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Osaka City General Hospital	Osaka
Japan	Osaka International Cancer Institute	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Sendai Kousei Hospital	Sendai	Miyagi
Japan	Tokyo Metropolitan Police Hospital	Tokyo
Japan	Kanagawa cancer center	Yokohama	Kanagawa
Japan	Tottori University Hospital	Yonago	Tottori
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungcheongbuk-do [Chungbuk]
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Kyonggi-do
Korea, Republic of	Asan Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Samsung Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seoul-teukbyeolsi [Seoul]
Netherlands	Local Institution - 0216	Amsterdam	Noord-Holland
Netherlands	Local Institution - 0215	Groningen
Poland	Instytut Genetyki i Immunologii GENIM	Lublin	Lubelskie
Poland	Warminsko - Mazurskie Centrum Chorób Pluc w Olsztynie	Olsztyn	Warminsko-mazurskie
Romania	Institutul Oncologic Bucuresti	Bucharest	Bucure?ti
Romania	Centrul medical Focus	Bucure?ti
Romania	Institutul Oncologic Cluj	Cluj
Romania	Centrul de Oncologie "Sfântul Nectarie"	Craiova	Dolj
Romania	S.C. Centrul de Oncologie Euroclinic S.R.L.	Ia?i
Spain	CHUAC-Hospital Teresa Herrera	A Coruña	A Coruña [La Coruña]
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [Barcelona]
Spain	Hospital Universitario 12 de Octubre	Madrid	Madrid, Comunidad De
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid, Comunidad De
Spain	H.R.U Málaga - Hospital General	Málaga
Spain	CHUS - Hospital Clinico Universitario	Santiago de Compostela	A Coruña [La Coruña]
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Universitari i Politecnic La Fe	València
Switzerland	Kantonspital Baden	Baden	Aargau
Turkey	Local Institution - 0088	Adana
Turkey	Local Institution - 0084	Ankara
Turkey	Local Institution - 0083	Istanbul
Turkey	Local Institution - 0097	Istanbul
Turkey	Local Institution - 0085	Sakarya
Turkey	Local Institution - 0087	Stanbul	Istanbul
Turkey	Local Institution - 0086	Yenimahalle	Ankara
United States	Local Institution - 0136	Augusta	Georgia
United States	Local Institution - 0075	Boston	Massachusetts
United States	Local Institution - 0201	Boston	Massachusetts
United States	Local Institution - 0217	Brooklyn	New York
United States	Local Institution - 0221	Des Moines	Iowa
United States	Local Institution - 0061	Milwaukee	Wisconsin
United States	Local Institution - 0210	Mineola	New York
United States	Laura and Isaac Perlmutter Cancer Center	New York	New York
United States	Local Institution - 0127	Syracuse	New York
United States	Local Institution - 0214	Tacoma	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Zai Lab (Shanghai) Co., Ltd.

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Brazil,  Canada,  Chile,  China,  France,  Germany,  Greece,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Romania,  Spain,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)		Up to 87 months
Secondary	Overall Response Rate (ORR) as per BICR according to RECIST v1.1		Up to 64 months
Secondary	ORR as per Investigator according to RECIST v1.1		Up to 64 months
Secondary	Duration of Response (DOR) as per BICR according to RECIST v1.1		Up to 64 months
Secondary	DOR as per Investigator according to RECIST v1.1		Up to 64 months
Secondary	Time to Response (TTR) as per BICR according to RECIST v1.1		Up to 64 months
Secondary	TTR as per Investigator according to RECIST v1.1		Up to 64 months
Secondary	PFS as per Investigator according to RECIST v1.1		Up to 64 months
Secondary	Time to intracranial progressions as per BICR according to RECIST v1.1		Up to 64 months
Secondary	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
Secondary	Number of deaths		Up to 30 days after last dose
Secondary	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

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting