A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases

NCT04603807 | Active Not Recruiting Phase 3 FDA Drug

• 3 other identifiers: MO415522019-003859-112023-507494-18-00
• Study Type: interventional
• Target: 220
• Locations: 18 countries
• Sites: 63

Brief Summary

The study will compare the efficacy and safety of entrectinib with crizotinib in participants with advanced or metastatic ROS1 non-small cell lung cancer (NSCLC). The participants will self-administer oral entrectinib or crizotinib as described in the protocol and local prescribing information. Treatments will continue until progressive disease, unacceptable toxicity, death, or withdrawal from the study, whichever occurs first.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

ROS1 Non-small-cell lung

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) in participants with central nervous system (CNS) metastases at baseline

  PFS is defined as the time from randomization to the first documented disease progression (extracranial or intracranial) or death from any cause whichever occurs first determined by a blinded independent review committee (BIRC) using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

  Up to 7 years

Secondary Outcomes (10)

• Progression-free survival in the Central Nervous System (CNS-PFS)

  Up to 7 Years

• Overall response rate (ORR)

  Up to 7 Years

• Duration of response (DOR)

  Up to 7 Years

• Progression-free survival (PFS)

  Up to 7 years

• Overall survival (OS)

  Up to 7 Years

Other Outcomes (1)

• Change in the scores of EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L)

  Up to 7 Years

Study Arms (2)

Entrectinib

EXPERIMENTAL

Participants will be enrolled to receive 600 mg entrectinib orally once daily until progressive disease, unacceptable toxicity, death, or withdrawal from the study, whichever occurs first.

Drug: Entrectinib

Crizotinib

ACTIVE COMPARATOR

Participants will be enrolled to receive 250 mg crizotinib orally twice daily until progressive disease, unacceptable toxicity, death, or withdrawal from the study, whichever occurs first.

Drug: Crizotinib

Interventions

Entrectinib DRUG

Entrectinib will be self-administered orally at a dose of 600 mg (three 200 mg capsules per day) once daily with or without food.

Entrectinib

Crizotinib DRUG

Crizotinib will be self-administered orally at a dose of 250 mg twice daily with or without food.

Crizotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (63)

Oncocentro Serviços Médicos e Hospitalares Ltda

Fortaleza, Ceará, 60130-241, Brazil

Location

Hospital Sao Rafael - HSR

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Hospitais Integrados da Gavea S/A

Brasília, Federal District, 70390-140, Brazil

Location

Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN

Florianópolis, Santa Catarina, 88020-210, Brazil

Location

Hospital de Cancer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

Oncoclinicas Rio de Janeiro S.A.

Rio de Janeiro, 22250-905, Brazil

Location

Jilin Cancer Hospital

Changchun, 132013, China

Location

The Second Xiangya Hospital of Central South University

Changsha, 410011, China

Location

Hunan Cancer Hospital

Changsha, 410013, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, 510120, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Affiliated Hospital of Jining Medical University

Jining, 272029, China

Location

Guangxi Cancer Hospital of Guangxi Medical University

Nanning, 530021, China

Location

Shanghai Pulmonary Hospital

Shanghai, 200433, China

Location

Taihe Hospital of Hubei University of Medicine

Shiyan, 442000, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430048, China

Location

Clinical Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

Institut Bergonie

Bordeaux, 33076, France

Location

CHRU Lille

Lille, 59037, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Hopital Nord AP-HM

Marseille, 13015, France

Location

CHU Rennes - Hopital Pontchaillou

Rennes, 35033, France

Location

Hopital Larrey

Toulouse, 31059, France

Location

Hopital Robert Schuman

Vantoux, 57070, France

Location

HELIOS Klinikum Emil von Behring Klinik f.Pneumologie Onkologie u.Infektiologie

Berlin, 14165, Germany

Location

Pius-Hospital

Oldenburg, 26121, Germany

Location

Metropolitan Hospital

Athens, 185 47, Greece

Location

MVR Cancer Centre and Research Institute

Kozhikode, Kerala, 673601, India

Location

MOC Cancer Care & Research Centre (Unit of Cellcure Cancer Centre Pvt Ltd)

Mumbai, Maharashtra, 400036, India

Location

All India Institute Of Medical Sciences (AIIMS)

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Mahamana Pandit Madan Mohan Malaviya Cancer Centre-TMC

Varanasi, Uttar Pradesh, 221005, India

Location

Tata Medical Center

Kolkata, West Bengal, 700160, India

Location

Azienda Ospedaliera San Camillo Forlanini

Rome, Lazio, 00152, Italy

Location

IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST)

Genoa, Liguria, 16132, Italy

Location

Azienda Sanitaria Ospedaliera S Luigi Gonzaga

Orbassano, Piedmont, 10043, Italy

Location

IRCCS Istituto Oncologico Veneto (IOV)

Padua, Veneto, 35128, Italy

Location

King Hussein Cancer Center

Amman, 1269, Jordan

Location

Hotel Dieu de France

Beirut, Lebanon

Location

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, Jalisco, 44280, Mexico

Location

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), 03100, Mexico

Location

NKI/AvL

Amsterdam, 1066 CX, Netherlands

Location

UMC St Radboud

Nijmegen, 6525 GA, Netherlands

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Amethyst Cluj

Cluj County, 407280, Romania

Location

Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj Napoca

Cluj-Napoca, 400015, Romania

Location

Centrul de Oncologie Sfantul Nectarie

Craiova, 200542, Romania

Location

Emergency County Clinical Hospital Ploiesti

Ploieşti, Romania

Location

Univerzitna nemocnica Bratislava

Bratislava, 826 06, Slovakia

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, 15006, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Regional Universitario Carlos Haya

Málaga, 29010, Spain

Location

Karolinska Universitetssjukhuset, Solna

Stockholm, 171 76, Sweden

Location

Chulalongkorn Hospital

Bangkok, 10330, Thailand

Location

Faculty of Med. Siriraj Hosp.

Bangkok, 10700, Thailand

Location

Prapokklao Hospital

Chanthaburi, 22000, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Bangkok Metropolitan Administration Medical College and Vajira Hospital

Wachira Phayaban, 10300, Thailand

Location

Gazi University Medical Faculty, Oncology Hospital

Ankara, 06500, Turkey (Türkiye)

Location

Liv Hospital Ankara

Ankara, 06680, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

entrectinib; Crizotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2020
• First Posted: October 27, 2020
• Study Start: September 30, 2021
• Primary Completion (Estimated): June 26, 2028
• Study Completion (Estimated): June 26, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

DE (2); ES (5); TH (5); IT (4); TU (2); NL (3); CN (11); SE (1); GR (1); JO (1); ME (2); SL (1); LE (1); RO (4); IN (5); BR (7); CR (1); FR (7)