A Study to Evaluate and Compare the Efficacy and Safety of Alectinib Versus Crizotinib and to Evaluate the Pharmacokinetics of Alectinib in Asian Participants With Treatment-Naive Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC)

NCT02838420 | Active Not Recruiting Phase 3 Results FDA Drug

• 1 other identifier: YO29449
• Study Type: interventional
• Target: 187
• Locations: 3 countries
• Sites: 21

Brief Summary

This randomized, multicenter, Phase III, open-label study will evaluate the efficacy and safety of alectinib versus crizotinib and to evaluate the pharmacokinetics of alectinib in asian participants with treatment-naive ALK-positive advanced NSCLC. Participants will be randomized 2:1 into one of the two treatment groups to receive either alectinib (600 milligrams \[mg\] twice daily \[BID\]) or crizotinib (250 mg BID) orally, respectively.

Conditions

Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumor (RECIST) v1.1

  PFS was defined as the time (in months) from randomization to the first documentation of disease progression, as determined by the investigators, or to death from any cause, whichever occurred first.

  From the date of randomization to the date of the first documented disease progression or death, whichever occurred first (up to overall period of approximately 40 months)

Secondary Outcomes (12)

• PFS as Determined by Independent Review Committee (IRC) Using RECIST v1.1

  Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)

• Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by Investigator Using RECIST v1.1

  Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)

• Time to Progression of Disease in the CNS as Determined by IRC Using RECIST v1.1

  Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)

• Time to Progression of Disease in the CNS as Determined by IRC Using Response Assessment in Neuro-Oncology (RANO)

  Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)

• Duration of Response (DOR) Assessed by Investigator Using RECIST v1.1

  Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)

Study Arms (2)

Alectinib

EXPERIMENTAL

Participants will receive alectinib capsules orally at a dose of 600 mg BID with food until disease progression, unacceptable toxicity withdrawal of consent, or death.

Drug: Alectinib

Crizotinib

ACTIVE COMPARATOR

Participants will receive crizotinib capsules orally at a dose of 250 mg BID with or without food until disease progression, unacceptable toxicity withdrawal of consent, or death.

Drug: Crizotinib

Interventions

Alectinib DRUG

Alectinib capsules will be administered orally at a dose of 600 mg BID until disease progression, unacceptable toxicity withdrawal of consent, or death.

Also known as: RO5424802

Alectinib

Crizotinib DRUG

Crizotinib capsules will be administered orally at a dose of 250 mg BID 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. Sufficient tumor tissue available to perform ALK IHC is required. Ventana IHC testing will be performed at the designated central laboratory
• Life expectancy of at least 12 weeks
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
• No history of receiving systemic treatment for advanced, recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC
• Adequate hematologic function: Platelet count greater than equal to (\>=) 100×10\^9 per liter (/L); absolute neutrophil count (ANC) \>=1500 cells per microliter (cells/mcL); hemoglobin\>=9.0 grams per deciliter (g/dL)
• Adequate renal function: an estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula of \>=45 milliliters per minute per 1.73 square meter
• Participants must have recovered from effects of any major surgery or significant traumatic injury at least 28 days before receiving the first dose of study treatment
• Measurable disease (by Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]) before administration of study treatment
• Previous brain or leptomeningeal metastases are allowed if the participant is asymptomatic (e.g., diagnosed incidentally at study baseline). Asymptomatic central nervous system (CNS) lesions may be treated at the discretion of the investigator as per local clinical practice. If participant has neurological symptoms or signs because of CNS metastasis, the participant must complete whole-brain radiation or gamma knife irradiation treatment. In all cases, radiation treatment must be completed \>=14 days before enrollment and disease must be clinically stable
• For all females of childbearing potential, a negative serum pregnancy test result must be obtained within 3 days prior to starting study treatment
• For women who are not postmenopausal (\>=12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus), agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 3 months after the last dose of study drug. Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Examples of contraceptive methods with a failure rate of \<1% per year include tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of \<1% per year. Barrier methods must always be supplemented with the use of a spermicide
• For men, agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \<1% per year during the treatment period and for at least 3 months after the last dose of study drug. Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception

You may not qualify if:

• A malignancy within the previous 3 years (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, or any cured cancer that is considered to have no impact in progression-free survival (PFS) or overall survival (OS) for the current NSCLC)
• Any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post-major bowel resection
• Liver disease characterized by:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than (\>) 3× the upper limit of normal (ULN; \>=5×ULN for participants with concurrent liver metastases) confirmed on two consecutive measurements; or
• Impaired excretory function (e.g., hyperbilirubinemia), synthetic function, or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices; or
• Acute viral or active autoimmune, alcoholic, or other types of hepatitis
• National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 3 or higher toxicities because of any previous therapy (e.g., radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication
• History of organ transplant
• Co-administration of anti-cancer therapies other than those administered in this study
• Baseline QTc \>470 ms or symptomatic bradycardia
• Administration of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the receiving the first dose of study treatment and during treatment with alectinib or crizotinib
• Administration of agents with potential QT interval prolonging effects within 14 days prior to receiving the first dose of study drug
• History of hypersensitivity to any of the additives in the alectinib or crizotinib drug formulation
• Pregnant or lactating
• Known human immunodeficiency virus (HIV-positivity or acquired immunodeficiency syndrome (AIDS)-related illness

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (21)

Beijing Cancer Hospital

Beijing, 100142, China

Location

Beijing Chest Hospital

Beijing, 101149, China

Location

the First Hospital of Jilin University

Changchun, 130021, China

Location

Jilin Cancer Hospital

Changchun, 132013, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Sun Yet-sen University Cancer Center

Guangzhou, 510060, China

Location

Guangdong General Hospital

Guangzhou, 510080, China

Location

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, 510120, China

Location

The First Affiliated Hospital of College of Medicine, Zhejiang University

Hangzhou, 310003, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310022, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Jiangsu Cancer Hospital

Nanjing, 210009, China

Location

Shanghai chest hospital

Shanghai, 200030, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Shanghai Pulmonary Hospital

Shanghai, 200433, China

Location

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Rajavithi Hospital

Bangkok, 10400, Thailand

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Related Publications (1)

• Zhou C, Kim SW, Reungwetwattana T, Zhou J, Zhang Y, He J, Yang JJ, Cheng Y, Lee SH, Bu L, Xu T, Yang L, Wang C, Liu T, Morcos PN, Lu Y, Zhang L. Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study. Lancet Respir Med. 2019 May;7(5):437-446. doi: 10.1016/S2213-2600(19)30053-0. Epub 2019 Apr 10.

  PMID: 30981696 DERIVED

MeSH Terms

Interventions

alectinib; Crizotinib

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: July 18, 2016
• First Posted: July 20, 2016
• Study Start: August 3, 2016
• Primary Completion: May 31, 2018
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 18, 2026
• Results First Posted: July 11, 2019

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

KR (3); TH (3); CN (15)