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

Randomized, Multicenter, Phase III, Open-Label Study of Alectinib Versus Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer

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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Alectinib; Drug: Crizotinib

• Study Type: Interventional
• Enrollment (Actual): 303
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Kinghorn Cancer Centre
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • South Australia
    • Adelaide, South Australia, Australia, 5011
      • Queen Elizabeth Hospital
  • Victoria
    • Victoria, Victoria, Australia, 3168
      • Monash Health Translational Precinct
• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina, 71000
    • University Clinical Center Sarajevo
• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Odette Cancer Centre
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• Chile
  • Santiago, Chile, 8420383
    • Centro Internacional de Estudios Clínicos (CIEC)
• China
  • Guangzhou, China, 510060
    • Sun Yet-sen University Cancer Center
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital
• Costa Rica
  • San José, Costa Rica, DUMMY_VALUE
    • Clinica CIMCA
• Egypt
  • Cairo, Egypt, 11555
    • Kasr Eieny Uni Hospital
• France
  • Grenoble, France, 38043
    • Chu Grenoble - Hopital Albert Michallon
  • Lille, France, 59037
    • CHRU de Lille
  • Lyon, France, 69373
    • Centre Leon Berard
  • Pessac, France, 33604
    • Hopital Haut Leveque
• Guatemala
  • Guatemala City, Guatemala, 01015
    • Grupo Angeles
• Hong Kong
  • Hong Kong, Hong Kong, 852
    • Tuen Mun Hospital
  • Hong Kong, Hong Kong, DUMMY_VALUE
    • Pamela Youde Nethersole Eastern Hospital
  • Hong Kong, Hong Kong
    • Prince of Wales Hosp
  • Hong Kong, Hong Kong, DUMMY_VALUE
    • Princess Margaret Hospital
  • Hong Kong, Hong Kong, DUMMY_VALUE
    • Queen Mary Hospital
• Israel
  • Haifa, Israel, 4959381
    • Rambam Medical Center
  • Kfar Saba, Israel, 44281
    • Meir Medical Center
• Italy
  • Apulia
    • Bari, Apulia, Italy, 70124
      • Irccs Ist. Tumori Giovanni Paolo Ii
  • Emilia-Romagna
    • Parma, Emilia-Romagna, Italy, 43100
      • A.O. Universitaria Di Parma
    • Ravenna, Emilia-Romagna, Italy, 48100
      • Ospedale Provinciale Santa Maria Delle Croci
  • Lazio
    • Rome, Lazio, Italy, 00161
      • Policlinico Umberto i di Roma
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Irccs Istituto Nazionale Dei Tumori (Int)
    • Milan, Lombardy, Italy, 20141
      • Irccs Istituto Europeo Di Oncologia (IEO)
  • Piedmont
    • Orbassano, Piedmont, Italy, 10043
      • Azienda Ospedaliero-Universitaria San Luigi Gonzaga
  • Sicily
    • Catania, Sicily, Italy, 95122
      • Az Ospedaliera Nuovo Garibaldi Quartiere Nesima
  • Umbria
    • Perugia, Umbria, Italy, 06156
      • Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia
• Mexico
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 14080
      • Instituto Nacional De Enfermedades Respiratorias
• New Zealand
  • Auckland, New Zealand, DUMMY_VALUE
    • Uni of Auckland
• Poland
  • Gda?sk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Lublin, Poland, 20-064
    • Ms Clinsearch Specjalistyczny Niepubliczny Zaklad Opieki Zdrowotnej
  • Olsztyn, Poland, 10-357
    • Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie
  • Warsaw, Poland, 02-781
    • Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie
• Portugal
  • Coimbra, Portugal, 3000-075
    • CHUC - Unidade de Pneumologia Oncológica
  • Lisbon, Portugal, 1099-023
    • IPO de Lisboa
  • Porto, Portugal, 4200-072
    • IPO do Porto
• Russia
  • Moscow, Russia, 105229
    • N.N.Burdenko Main Military Clinical Hospital
  • Moscow Oblast
    • Moscovskaya Oblast, Moscow Oblast, Russia, 143423
      • Moscow City Oncology Hospital #62
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 197022
      • SPb City Clin Onc Dsp
    • Saint Petersburg, Sankt-Peterburg, Russia, 197758
      • Scientific Research Oncology Institute named after N.N. Petrov
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
  • Kamenitz, Serbia, 21204
    • Institute for pulmonary diseases of Vojvodina
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre
  • Singapore, Singapore, 119228
    • National University Hospital
• South Korea
  • Gyeonggi-do, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Gyeonggi-do, South Korea, 10408
    • National Cancer Center
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
• Spain
  • Alicante, Spain, 3010
    • Hospital General Univ. de Alicante
  • Barcelona, Spain, 08916
    • Hospital Universitari Germans Trias i Pujol
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institute of Oncology (VHIO), Barcelona
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
• Switzerland
  • Basel, Switzerland, 4031
    • Universitaetsspital Basel
  • Bern, Switzerland, 3010
    • Inselspital Bern
  • Lausanne, Switzerland, 1011
    • CHUV
  • Zurich, Switzerland, 8091
    • UniversitätsSpital Zürich
• Taiwan
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 00704
    • National Cheng Kung Univ Hosp
  • Taipei, Taiwan, 00100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 00112
    • Taipei Veterans General Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • National Cancer Inst.
  • Chiang Rai, Thailand, 57000
    • Chiang Rai Prachanukroh Hospital
  • Khonkaen, Thailand, 40000
    • Khonkaen Hospital
  • Patumwan, Thailand, 10330
    • King Chulalongkorn Memorial Hospital
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01250
    • Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital
  • Ankara, Turkey (Türkiye), 06100
    • Ankara University Medical Faculty
  • Edirne, Turkey (Türkiye), 22770
    • Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department
  • Malatya, Turkey (Türkiye), 44280
    • Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
• Ukraine
  • Kyiv, Ukraine, 04107
    • Kyiv Regional Oncological Dispensary
  • Lviv, Ukraine, 79031
    • Lviv State Oncology Regional Treatment and Diagnostic Centre
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • London, United Kingdom, NW1 - 2PG
    • University College London Hospital
  • London, United Kingdom, SE1 9RT
    • Guys & St Thomas Hospital
• United States
  • California
    • Northridge, California, United States, 91325
      • North Valley Hem Onc Med Grp
    • Redondo Beach, California, United States, 90277
      • TMPN/ Cancer Care Associates
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Florida
    • Deerfield Beach, Florida, United States, 33442
      • University of Miami-Deerfield Beach
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Med Ctr
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Can Ins
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington Uni School of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Scri Oncology Partners
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alectinib; Participants will receive alectinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Alectinib; 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.; Other Names: RO5424802
Active Comparator: Crizotinib; Participants will receive crizotinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Crizotinib; Participants will receive crizotinib 250 mg capsules orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS Independent Review Committee (IRC)-Assessed	PFS was assessed as time to disease progression or death whichever occurred first by IRC 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 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 IRC	PFS was assessed as percentage of participants with disease progression or death whichever occurred first by IRC 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 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 Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria	CNS progression was assessed as percentage of participants with an event defined as time from randomization until first radiographic evidence of CNS progression by IRC. The risk for a CNS progression without a prior non-CNS progression with alectinib compared with crizotinib.	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	CNS progression was assessed as percentage of participants with event defined as time from randomization until first radiographic evidence of CNS progression by IRC. The risk for a CNS progression without a prior non-CNS progression with alectinib compared with crizotinib.	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	ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria	CNS ORR was defined as the percentage of participants who attained CR or PR and had measurable/non-measurable CNS lesions at baseline. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
CNS DOR IRC-assessed According to RECIST v1.1 Criteria	CNS DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR.	First occurrence of CNS objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Area Under The Concentration-Time Curve (AUC) of Alectinib		Pre-dose (within 2 hours before alectinib) (baseline), 1, 2, 4, 6, and 8 hours post-dose at Visit 0 (first dosing day) and Week 4; Pre-dose (within 2 hours) at Week 8, then every 8 weeks until disease progression or death/withdrawal (up to 33 months)
Maximum Concentration (Cmax) of Alectinib		Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
Time to Reach Cmax (Tmax) of Alectinib		Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
AUC of Alectinib Metabolite		Pre-dose (within 2 hours before alectinib) (baseline), 1, 2, 4, 6, and 8 hours post-dose at Visit 0 (first dosing day) and Week 4; Pre-dose (within 2 hours) at Week 8, then every 8 weeks until disease progression or death/withdrawal (up to 33 months)
Cmax of Alectinib Metabolite		Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
Tmax of Alectinib Metabolite		Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30)	The EORTC QLQ-30 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in global health status or function is defined as a >or=10-point decrease from baseline in a symptom score that must be held for at least two consecutive assessments or an initial >or=10-point decrease from baseline followed by death within 5 weeks from the last assessment.	Baseline, every 4 weeks until disease progression (up to 33 months)
Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30)	The EORTC QLQ-30 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in global health status or function is defined as a >or=10-point decrease from baseline in a symptom score that must be held for at least two consecutive assessments or an initial >or=10-point decrease from baseline followed by death within 5 weeks from the last assessment.	Baseline, every 4 weeks until disease progression (up to 33 months)
Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a >or=10-point increase from baseline in a symptom score that must be held for at least two consecutive assessments or an initial >or=10-point increase above baseline followed by death within 5 weeks from the last assessment.	Baseline, every 4 weeks until disease progression (up to 33 months)
Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a >or=10-point increase from baseline in a symptom score that must be held for at least two consecutive assessments or an initial >or=10-point increase above baseline followed by death within 5 weeks from the last assessment.	Baseline, every 4 weeks until disease progression (up to 33 months)
Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score	The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators	DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR.	First occurrence of objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to approximately 10 years)
Overall Survival (OS)	Overall survival (OS) was defined as the time from randomization to death from any cause.	From randomization until death (up to 10.5 years)
Percentage of Participants With OS Event	Overall survival (OS) was defined as the time from randomization to death from any cause.	From randomization until death (up to 10.5 years)
Percentage of Participants With Adverse Events	An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Baseline up to approximately 10 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2014
• Primary Completion (Actual): February 9, 2017
• Study Completion (Actual): April 28, 2025

Study Registration Dates

• First Submitted: February 27, 2014
• First Submitted That Met QC Criteria: February 27, 2014
• First Posted (Estimated): March 3, 2014

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperidines; Aminopyridines; Crizotinib; alectinib
• Other Study ID Numbers: BO28984; 2013-004133-33 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No