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ALTA-1L Study: A Phase 3 Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-small Cell Lung Cancer (NSCLC) Participants (ALTA-1L)

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ClinicalTrials.gov Identifier: NCT02737501
Recruitment Status : Active, not recruiting
First Posted : April 14, 2016
Last Update Posted : April 11, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Ariad Pharmaceuticals )

Brief Summary:
A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) versus Crizotinib in ALK-positive Advanced Lung Cancer Participants.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Lung Cancer Advanced Malignancies Carcinoma Drug: Brigatinib Drug: Crizotinib Phase 3

Detailed Description:

The purpose of this phase III, randomized, open-label, comparative, multicenter, international study is to compare the efficacy and safety of brigatinib to that of crizotinib in ALK-positive locally advanced or metastatic NSCLC participants who have not previously been treated with an ALK inhibitor. Participants will be randomized in a 1:1 ratio to receive either brigatinib, 90 mg orally once daily (QD) for 7 days, then a 180 mg orally QD, or crizotinib, 250 mg orally twice daily (BID). Participants will receive treatment until disease progression, intolerable toxicity, consent withdrawal, or death.

The total estimated duration of the study is at least 5 years, including 2 years to accrue participants, with at least 3 years for treatment and follow-up.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 275 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) Versus Crizotinib in Patients With ALK-positive Advanced Lung Cancer
Actual Study Start Date : May 26, 2016
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : July 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Brigatinib
Brigatinib will be administered orally to eligible participants with locally advanced or metastatic ALK+NSCLC naive to ALK inhibitors at a dose of 90 milligram (mg) QD for 7 days, then 180 mg QD, continuously, with or without food until disease progression, unacceptable toxicity, withdrawal of consent or death.
Drug: Brigatinib
Brigatinib will be administered orally to eligible participants with locally advanced or metastatic ALK+NSCLC naive to ALK inhibitors at a dose of 90 mg QD for 7 days, then 180 mg QD, continuously, until disease progression, unacceptable toxicity, withdrawal of consent or death.

Active Comparator: Crizotinib
Crizotinib will be administered to eligible participants with locally advanced or metastatic ALK+ NSCLC naive to ALK inhibitors as 250 mg orally BID, with or without food until disease progression, unacceptable toxicity, withdrawal of consent or death.
Drug: Crizotinib
Crizotinib will be administered to eligible participants with locally advanced or metastatic ALK+ NSCLC naive to ALK inhibitors as 250 mg orally BID, until disease progression, unacceptable toxicity, withdrawal of consent or death.
Other Name: Xalkori




Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Baseline up to approximately 36 months ]
    PFS as assessed by blinded Independent Review Committee (BIRC) is defined as the time interval from the date of randomization until the first date at which disease progression (PD) is objectively documented, or death due to any cause, whichever occurs first. PD is sum of longest diameter (SLD) increased by at least 20 percent (%) from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 millimeter (mm), and unequivocal progression of existing non-target lesions.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Baseline up to approximately 36 months ]
    ORR as assessed by BIRC, is defined as percentage of participants who are confirmed to have achieved complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v). 1.1 criteria. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to less than (<) 10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in SLD of target lesions, taking as reference baseline sum diameters. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions.

  2. Intracranial ORR [ Time Frame: Baseline up to approximately 36 months ]
    Intracranial ORR as assessed by BIRC, is defined as the percentage of the participants who have achieved CR or PR in the central nervous system (CNS) in randomized participants with intracranial CNS metastasis at baseline. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions.

  3. Intracranial PFS [ Time Frame: Baseline up to approximately 36 months ]
    Intracranial PFS as assessed by BIRC, is defined as the time from randomization until first CNS PD is documented, or death due to any cause. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions.

  4. Overall Survival (OS) [ Time Frame: Baseline up to approximately 36 months ]
    Overall survival is defined as the time from randomization until death due to any cause.

  5. Duration of Response [ Time Frame: Baseline up to approximately 36 months ]
    Duration of response as assessed by BIRC, is defined as the time interval from the date that the criteria are first met for CR/PR (whichever is first recorded) until the first date that progressive disease (PD) is objectively documented. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30 % decrease in the SLD of target lesions, taking as reference the baseline sum diameters. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and for non-target lesions, unequivocal progression of existing non-target lesions.

  6. Time to Response (TTR) [ Time Frame: Baseline up to approximately 36 months ]
    Time to response as assessed by BIRC, assessment and is defined as the time interval from the date randomization until the initial observation of CR or PR. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters.

  7. Disease Control Rate (DCR) [ Time Frame: Baseline up to approximately 36 months ]
    Disease control as assessed by BIRC, defined as percentage of randomized participants who have achieved CR, PR, or stable disease (SD) (in the case of SD, criteria for SD must have been met at least once after randomization at a minimum interval of 6 weeks) after randomization. CR defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR: at least a 30% decrease in SLD of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: SLD increased by at least 20% from the smallest value on study, SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions.

  8. Health-related Quality of Life (HRQoL) [ Time Frame: Baseline until 30 days after the last dose of study treatment (approximately 3 years) ]
    HRQoL is defined as the perceived quality of the participant's life, which includes self-reported multidimensional measures of physical and mental health. Patient-reported symptoms (PROs) and HRQoL will be collected by administering the european organisation for research and treatment of cancer (EORTC) quality of life (QLQ)-C30 questionnaire. EORTC-QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. The 30 items have 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Raw scores are converted into scale scores ranging from 0 to 100. For functional scales and QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.

  9. Percentage of Participants with Adverse Events [ Time Frame: Baseline until 30 days after the last dose of study treatment (approximately 3 years) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Have histologically or cytologically confirmed stage IIIB (and not a candidate for definitive multimodality therapy) or stage four (IV) NSCLC.
  2. Must have documented ALK rearrangement.
  3. Have sufficient tumor tissue available for central analysis.
  4. Have at least 1 measurable (that is, target) lesion per RECIST v1.1.
  5. Recovered from toxicities related to prior anticancer therapy to National Cancer Institute (of the United States) (NCI) Common Terminology Criteria for Adverse Events (version 4.0) (CTCAE v 4.0) grade be less than or equal to (<=) 1.
  6. Are a male or female participants greater than or equal to (>=)18 years old.
  7. Have adequate organ function, as defined by the study protocol.
  8. Have Eastern Cooperative Oncology Group (ECOG) performance status <=2.
  9. Have normal QT interval on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of <= 450 millisecond (msec) in males or <=470 msec in females.
  10. For female participants of childbearing potential, have a negative pregnancy test documented prior to randomization.
  11. For female and male participants who are fertile, agree to use a highly effective form of contraception, as defined by the study protocol.
  12. Provide signed and dated informed consent indicating that the participants has been informed of all pertinent aspects of the study, including the potential risks, and is willingly participating.
  13. Have the willingness and ability to comply with scheduled visit and study procedures.

Exclusion Criteria:

  1. Previously received an investigational antineoplastic agent for NSCLC.
  2. Previously received any prior tyrosine kinase inhibitor (TKI), including ALK-targeted TKIs.
  3. Previously received more than 1 regimen of systemic anticancer therapy for locally advanced or metastatic disease.
  4. Received chemotherapy or radiation within 14 days of first dose of study drug, except stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT).
  5. Received anti-neoplastic monoclonal antibodies within 30 days of the first dose of study drug.
  6. Had major surgery within 30 days of the first dose of study drug, minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.
  7. Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or participants with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
  8. Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within 7 days prior to randomization.
  9. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed.
  10. Be pregnant, planning a pregnancy, or breastfeeding.
  11. Have significant, uncontrolled, or active cardiovascular disease, as defined by the study protocol.
  12. Have uncontrolled hypertension.
  13. Have a history or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis.
  14. Have an ongoing or active infection.
  15. Have a known history of human immunodeficiency virus (HIV) infection.
  16. Have a known or suspected hypersensitivity to brigatinib or its excipients and/or crizotinib or its excipients.
  17. Have malabsorption syndrome or other gastrointestinal (GI) illness or condition.
  18. Have any condition or illness that, in the opinion of the investigator, would compromise participant's safety or interfere with the evaluation of the study drug.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02737501


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Locations
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United States, Arizona
USOR - Arizona Oncology Associates - Sedona
Sedona, Arizona, United States, 86336
United States, California
Kaiser Permanente Bellflower Medical Offices
Bellflower, California, United States, 90706
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
Rocky Mountain Cancer Centers - Boulder
Boulder, Colorado, United States, 80303-1385
United States, Florida
Sylvester Comprehensive Cancer Center
Deerfield Beach, Florida, United States, 33442
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007
United States, Minnesota
Minnesota Oncology
Coon Rapids, Minnesota, United States, 55433
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10461
United States, Ohio
Oncology Hematology Care - Blue Ash
Cincinnati, Ohio, United States, 45242-5665
United States, Oklahoma
Stephenson Cancer Center
Oklahoma City, Oklahoma, United States, 73104
United States, Virginia
Virginia Cancer Specialists - Fairfax Office
Fairfax, Virginia, United States, 22031
Australia, New South Wales
Saint George Hospital
Kogarah, New South Wales, Australia, 2217
Royal North Shore Hospital
St Leonards, New South Wales, Australia, 2065
Australia, Victoria
Monash Medical Centre
East Bentleigh, Victoria, Australia, 3165
Saint Vincent's Hospital Melbourne
Fitzroy, Victoria, Australia, 3065
Austria
Universitatsklinium St. Polten
Sankt Polten, Lower Austria, Austria, 3100
Otto-Wagner-Spital Baumgartner Hohe
Vienna, Austria, 1140
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Denmark
Odense University Hospital
Odense C, Denmark, 5000
France
Centre de Lutte Contre le Cancer Francois Baclesse
CAEN Cedex 5, Basse-normandie, France, 14076
Hopital Charles Nicolle
Rouen, Haute-normandie, France, 76041
Centre Hospitalier Intercommunal de Creteil
Creteil, Ile-de-france, France, 94010
Hopital Tenon
Paris, Ile-de-france, France, 75020
Centre Hospitalier Universitaire Hopital Nord
Marseille Cedex 20, Provence Alpes COTE D'azur, France, 13915
Hopital Albert Michallon
Grenoble Cedex 9, Rhone-alpes, France, 38043
Centre Leon Berard
Lyon, Rhone-alpes, France, 69008
Germany
Universitatsklinik Freiburg
Freiburg, Baden-wuerttemberg, Germany, 79106
Thoraxklinik Heidelberg gGmbH
Heidelberg, Baden-wuerttemberg, Germany, 69126
Pius Hospital Oldenburg
Oldenburg, Niedersachsen, Germany, 26121
Kliniken der Stadt Koeln gGmbH - Krankenhaus Merheim
Koln, Nordrhein-westfalen, Germany, 51109
Evangelische Lungenklinik Berlin
Berlin, Germany, 13125
Studiengesellschaft Haemato-Onkologie Hamburg Prof. Laack und Partner
Hamburg, Germany, 20251
Hong Kong
Tuen Mun Hospital
Tuen Mun, New Territories, Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong
Queen Elizabeth Hospital
Kowloon, Hong Kong, 150001
Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, Forli-cesena, Italy, 47014
Azienda Ospedaliera San Gerardo di Monza
Monza, Monza E Brianza, Italy, 20052
Centro di Riferimento Oncologico di Aviano
Aviano, Pordenone, Italy, 33081
Azienda Ospedaliera San Giuseppe Moscati
Avellino, Italy, 83100
Istituto Oncologico di Bari Giovanni Paolo II
Bari, Italy, 70124
Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
Bologna, Italy, 40138
Istituto Scientifico Universitario San Raffaele
Milano, Italy, 20132
Istituto Europeo di Oncologia
Milano, Italy, 20141
Istituto Tumori Napoli Fondazione G. Pascale
Napoli, Italy, 80131
Azienda Ospedaliero Universitaria Maggiore della Carita
Novara, Italy, 28100
Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia
Perugia, Italy, 06132
Azienda Unita Sanitaria Locale di Ravenna
Ravenna, Italy, 48121
Policlinico Universitario Campus Bio-Medico
Roma, Italy, 00128
Korea, Republic of
Chungbuk National University Hospital
Cheongju, Chungcheongbuk-do, Korea, Republic of, 28644
National Cancer Center
Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Severance Hospital
Seoul, Korea, Republic of, 03722
Asan Medical Center
Seoul, Korea, Republic of, 05505
Samsung Medical Center
Seoul, Korea, Republic of, 06351
The Catholic University of Korea
Seoul, Korea, Republic of, 06591
Luxembourg
Centre Hospitalier de Luxembourg - Hopital Municipal
Luxembourg, Luxembourg, 1210
Netherlands
Amphia Ziekenhuis - Locatie Langendijk Breda
Breda, Noord-brabant, Netherlands, 4818 CK
Antoni van Leeuwenhoekziekenhuis
Amsterdam, Noord-holland, Netherlands, 1066 CX
Isala Klinieken
Zwolle, Overijssel, Netherlands, 8025 AB
Universitair Medisch Centrum Groningen
Groningen, Netherlands, 9713 GZ
Norway
Radiumhospitalet
Oslo, Norway, 0379
Singapore
National University Hospital
Singapore, Singapore, 119228
National Cancer Centre Singapore
Singapore, Singapore, 169610
OncoCare Cancer Centre
Singapore, Singapore, 258499
Spain
Hospital Universitario Central de Asturias
Oviedo, Asturias, Spain, 33011
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Hospital Universitario Puerta de Hierro - Majadahonda
Majadahonda, Madrid, Spain, 28222
Hospital General Universitario de Alicante
Alicante, Spain, 03010
Hospital Universitario Vall d'Hebron
Barcelona, Spain, 08035
Hospital Teresa Herrera - Materno Infantil
La Coruna, Spain, 15006
Hospital Ramon Y Cajal
Madrid, Spain, 28034
Hospital Universitario La Paz
Madrid, Spain, 28046
Hospital Regional Universitario Carlos Haya Malaga Instituto de Neurociencias Clinicas
Malaga, Spain, 29010
Hospital Universitario Marques de Valdecilla
Santander, Spain, 39008
Hospital Universitario Virgen del Rocio
Sevilla, Spain, 41013
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
Sweden
Karolinska Universitetssjukhuset
Stockholm, Sweden, 171 76
Switzerland
University Hospital Zurich
Zurich, Switzerland, 8091
Taiwan
National Cheng Kung University
Tainan, Taipei, Taiwan, 70403
China Medical University Hospital
Taichung, Taiwan, 404
Taichung Veterans General Hospital
Taichung, Taiwan, 40705
National Taiwan University Hospital
Taipei, Taiwan, 100
Taipei Veterans General Hospital
Taipei, Taiwan, 11217
United Kingdom
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
University College London
London, England, United Kingdom, NW1 2PG
Guy's and Saint Thomas' NHS Foundation Trust
London, England, United Kingdom, SE1 9RT
Royal Marsden NHS Trust
London, England, United Kingdom, SW3 6JJ
Maidstone Hospital
Maidstone, England, United Kingdom, ME16 9QQ
The Christie NHS Foundation Trust
Manchester, England, United Kingdom, M20 4BX
Sponsors and Collaborators
Ariad Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02737501     History of Changes
Other Study ID Numbers: AP26113-13-301
U1111-1210-4363 ( Other Identifier: World Health Organization )
First Posted: April 14, 2016    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Ariad Pharmaceuticals ):
Non-small cell lung cancer
Non-small cell lung carcinoma
Epithelial lung cancer
Squamous cell carcinoma
Large cell carcinoma
Adenocarcinoma
Carcinoma
Anaplastic Lymphoma Kinase (ALK)
Advanced Cancers
Brigatinib
AP26113
Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Crizotinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action