A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants

NCT02075840 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: BO289842013-004133-33
• Study Type: interventional
• Target: 303
• Locations: 29 countries
• Sites: 98

Brief Summary

This randomized, active controlled, multicenter phase III open-label study is designed to evaluate the efficacy and safety of alectinib compared with crizotinib treatment in participants with treatment-naive anaplastic lymphoma kinase-positive (ALK-positive) advanced non-small cell lung cancer (NSCLC). Participants will be randomized in a 1:1 ratio to receive either alectinib, 600 milligrams (mg) orally twice daily (BID), or crizotinib, 250 mg orally BID. Participants will receive treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death. The study is expected to last approximately 144 months.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS) by Investigator Assessment

  PFS was assessed as time to disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.

  Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)

• Percentage of Participants With PFS Event by Investigator Assessment

  PFS was assessed percentage of participants with disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.

  Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)

Secondary Outcomes (26)

• PFS Independent Review Committee (IRC)-Assessed

  Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)

• Percentage of Participants With PFS Event by IRC

  Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)

• Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria

  Randomization to CNS PD as first occurrence of disease progression (assessed every 8 weeks up to 33 months)

• Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria

  Randomization to the first occurrence of disease progression in the CNS (assessed every 8 weeks up to 33 months)

• Percentage of Participants With Objective Response Rate (ORR) of Complete Response (CR) or Partial Response (PR) as Determined by The Investigators According to RECIST V1.1 Criteria

  Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)

Study Arms (2)

Alectinib

EXPERIMENTAL

Participants will receive alectinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Drug: Alectinib

Crizotinib

ACTIVE COMPARATOR

Participants will receive crizotinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Drug: Crizotinib

Interventions

Alectinib DRUG

Participants will receive alectinib 600 mg orally (four 150 mg capsules) BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Also known as: RO5424802

Alectinib

Crizotinib DRUG

Participants will receive crizotinib 250 mg capsules orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

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 not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive as assessed by the Ventana immunohistochemistry (IHC) test
• Life expectancy of at least 12 weeks
• Eastern cooperative oncology group performance status (ECOG PS) of 0-2
• Participants with no prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC
• Adequate renal, and hematologic function
• 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
• Measurable disease by response evaluation criteria in solid tumors (RECIST) version 1.1 (v1.1) prior to the administration of study treatment
• Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed incidentally at study baseline)
• Negative pregnancy test for all females of child bearing potential
• Use of highly effective contraception as defined by the study protocol

You may not qualify if:

• Participants with a previous malignancy within the past 3 years
• Any gastrointestinal (GI) disorder or liver disease
• National cancer institute common terminology criteria for adverse events (NCI CTCAE) (version 4.0) Grade 3 or higher toxicities due to any prior therapy (e.g., radiotherapy) (excluding alopecia)
• History of organ transplant
• Co-administration of anti-cancer therapies other than those administered in this study
• Participants with baseline QTc greater than (\>) 470 milliseconds or symptomatic bradycardia
• Recipient of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose until the end of study treatment
• Recipient of any drug with potential QT interval prolonging effects within 14 days prior to the first dose for all participants and while on treatment through the end of the study for crizotinib-treated participants only
• History of hypersensitivity to any of the additives in the alectinib and crizotinib drug formulation
• Pregnancy or lactation
• Any clinically significant disease or condition (or history of) that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the principal investigator, pose an unacceptable risk to the participant in this study
• Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the participant before trial entry

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (98)

North Valley Hem Onc Med Grp

Northridge, California, 91325, United States

Location

TMPN/ Cancer Care Associates

Redondo Beach, California, 90277, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

University of Miami-Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Med Ctr

Boston, Massachusetts, 02215, United States

Location

Dana Farber Can Ins

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington Uni School of Medicine

St Louis, Missouri, 63110, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Kinghorn Cancer Centre

Darlinghurst, New South Wales, 2010, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

Queen Elizabeth Hospital

Adelaide, South Australia, 5011, Australia

Location

Monash Health Translational Precinct

Victoria, Victoria, 3168, Australia

Location

University Clinical Center Sarajevo

Sarajevo, 71000, Bosnia and Herzegovina

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Sunnybrook Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Centro Internacional de Estudios Clínicos (CIEC)

Santiago, 8420383, Chile

Location

Sun Yet-sen University Cancer Center

Guangzhou, 510060, China

Location

Shanghai Pulmonary Hospital

Shanghai, 200433, China

Location

Clinica CIMCA

San José, DUMMY_VALUE, Costa Rica

Location

Kasr Eieny Uni Hospital

Cairo, 11555, Egypt

Location

Chu Grenoble - Hopital Albert Michallon

Grenoble, 38043, France

Location

CHRU de Lille

Lille, 59037, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Hopital Haut Leveque

Pessac, 33604, France

Location

Grupo Angeles

Guatemala City, 01015, Guatemala

Location

Tuen Mun Hospital

Hong Kong, 852, Hong Kong

Location

Pamela Youde Nethersole Eastern Hospital

Hong Kong, DUMMY_VALUE, Hong Kong

Location

Princess Margaret Hospital

Hong Kong, DUMMY_VALUE, Hong Kong

Location

Queen Mary Hospital

Hong Kong, DUMMY_VALUE, Hong Kong

Location

Prince of Wales Hosp

Hong Kong, Hong Kong

Location

Rambam Medical Center

Haifa, 4959381, Israel

Location

Meir Medical Center

Kfar Saba, 44281, Israel

Location

Irccs Ist. Tumori Giovanni Paolo Ii

Bari, Apulia, 70124, Italy

Location

A.O. Universitaria Di Parma

Parma, Emilia-Romagna, 43100, Italy

Location

Ospedale Provinciale Santa Maria Delle Croci

Ravenna, Emilia-Romagna, 48100, Italy

Location

Policlinico Umberto i di Roma

Rome, Lazio, 00161, Italy

Location

Irccs Istituto Nazionale Dei Tumori (Int)

Milan, Lombardy, 20133, Italy

Location

Irccs Istituto Europeo Di Oncologia (IEO)

Milan, Lombardy, 20141, Italy

Location

Azienda Ospedaliero-Universitaria San Luigi Gonzaga

Orbassano, Piedmont, 10043, Italy

Location

Az Ospedaliera Nuovo Garibaldi Quartiere Nesima

Catania, Sicily, 95122, Italy

Location

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia

Perugia, Umbria, 06156, Italy

Location

Instituto Nacional De Enfermedades Respiratorias

Mexico City, Mexico CITY (federal District), 14080, Mexico

Location

Uni of Auckland

Auckland, DUMMY_VALUE, New Zealand

Location

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214, Poland

Location

Ms Clinsearch Specjalistyczny Niepubliczny Zaklad Opieki Zdrowotnej

Lublin, 20-064, Poland

Location

Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie

Olsztyn, 10-357, Poland

Location

Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie

Warsaw, 02-781, Poland

Location

CHUC - Unidade de Pneumologia Oncológica

Coimbra, 3000-075, Portugal

Location

IPO de Lisboa

Lisbon, 1099-023, Portugal

Location

IPO do Porto

Porto, 4200-072, Portugal

Location

Moscow City Oncology Hospital #62

Moscovskaya Oblast, Moscow Oblast, 143423, Russia

Location

SPb City Clin Onc Dsp

Saint Petersburg, Sankt-Peterburg, 197022, Russia

Location

Scientific Research Oncology Institute named after N.N. Petrov

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

N.N.Burdenko Main Military Clinical Hospital

Moscow, 105229, Russia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Institute for pulmonary diseases of Vojvodina

Kamenitz, 21204, Serbia

Location

National University Hospital

Singapore, 119228, Singapore

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

National Cancer Center

Gyeonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital General Univ. de Alicante

Alicante, 3010, Spain

Location

Vall d'Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035, Spain

Location

Hospital Universitari Germans Trias i Pujol

Barcelona, 08916, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, 28222, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Universitaetsspital Basel

Basel, 4031, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

CHUV

Lausanne, 1011, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung Univ Hosp

Tainan, 00704, Taiwan

Location

National Taiwan University Hospital

Taipei, 00100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 00112, Taiwan

Location

National Cancer Inst.

Bangkok, 10400, Thailand

Location

Chiang Rai Prachanukroh Hospital

Chiang Rai, 57000, Thailand

Location

Khonkaen Hospital

Khonkaen, 40000, Thailand

Location

King Chulalongkorn Memorial Hospital

Patumwan, 10330, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital

Adana, 01250, Turkey (Türkiye)

Location

Ankara University Medical Faculty

Ankara, 06100, Turkey (Türkiye)

Location

Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department

Edirne, 22770, Turkey (Türkiye)

Location

Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

Malatya, 44280, Turkey (Türkiye)

Location

Kyiv Regional Oncological Dispensary

Kyiv, 04107, Ukraine

Location

Lviv State Oncology Regional Treatment and Diagnostic Centre

Lviv, 79031, Ukraine

Location

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

University College London Hospital

London, NW1 - 2PG, United Kingdom

Location

Guys & St Thomas Hospital

London, SE1 9RT, United Kingdom

Location

Related Publications (7)

• Sikkema BJ, Baart SJ, Paats MS, Smit EF, Schols AMWJ, Mathijssen RHJ, van Rossum EFC, Dingemans AC. Body Weight Gain Associated With Alectinib in Patients With ALK+ Non-Small Cell Lung Cancer: Pooled Analysis of Individual Patient Data From Four Prospective Clinical Trials. J Clin Oncol. 2025 Feb 20;43(6):641-650. doi: 10.1200/JCO-24-01579. Epub 2024 Dec 11.

  PMID: 39661917 DERIVED

• Dziadziuszko R, Peters S, Mok T, Camidge DR, Gadgeel SM, Ou SI, Konopa K, Noe J, Nowicka M, Bordogna W, Morcos PN, Smoljanovic V, Shaw AT. Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non-small Cell Lung Cancer in the Global Phase III ALEX Trial. Clin Cancer Res. 2022 May 2;28(9):1800-1808. doi: 10.1158/1078-0432.CCR-21-2840.

  PMID: 35275991 DERIVED

• Mok T, Camidge DR, Gadgeel SM, Rosell R, Dziadziuszko R, Kim DW, Perol M, Ou SI, Ahn JS, Shaw AT, Bordogna W, Smoljanovic V, Hilton M, Ruf T, Noe J, Peters S. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020 Aug;31(8):1056-1064. doi: 10.1016/j.annonc.2020.04.478. Epub 2020 May 11.

  PMID: 32418886 DERIVED

• Gadgeel S, Peters S, Mok T, Shaw AT, Kim DW, Ou SI, Perol M, Wrona A, Novello S, Rosell R, Zeaiter A, Liu T, Nuesch E, Balas B, Camidge DR. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol. 2018 Nov 1;29(11):2214-2222. doi: 10.1093/annonc/mdy405.

  PMID: 30215676 DERIVED

• Burudpakdee C, Wong W, Seetasith A, Corvino FA, Yeh W, Gubens M. Economic impact of preventing brain metastases with alectinib in ALK-positive non-small cell lung cancer. Lung Cancer. 2018 May;119:103-111. doi: 10.1016/j.lungcan.2018.03.008. Epub 2018 Mar 9.

  PMID: 29656744 DERIVED

• Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Perol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T; ALEX Trial Investigators. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Aug 31;377(9):829-838. doi: 10.1056/NEJMoa1704795. Epub 2017 Jun 6.

  PMID: 28586279 DERIVED

• Gainor JF, Shaw AT. J-ALEX: alectinib versus crizotinib in ALK-positive lung cancer. Lancet. 2017 Jul 1;390(10089):3-4. doi: 10.1016/S0140-6736(17)31074-7. Epub 2017 May 10. No abstract available.

  PMID: 28501139 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

alectinib; 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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: February 27, 2014
• First Posted: March 3, 2014
• Study Start: August 19, 2014
• Primary Completion: February 9, 2017
• Study Completion: April 28, 2025
• Last Updated: July 25, 2025
• Results First Posted: March 15, 2018

Record last verified: 2025-07

Locations

KR (6); NZ (1); GU (1); PL (4); CN (2); PT (3); AU (5); RU (4); IT (9); SE (2); TH (5); IL (2); CO (1); UA (2); GB (3); BO (1); CH (4); EG (1); SG (2); BR (1); HK (5); TW (4); CL (1); FR (4); ME (1); CA (4); ES (5); TU (4); US (11)