A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC

A PHASE 3, RANDOMIZED, OPEN-LABEL STUDY OF LORLATINIB (PF-06463922) MONOTHERAPY VERSUS CRIZOTINIB MONOTHERAPY IN THE FIRST-LINE TREATMENT OF PATIENTS WITH ADVANCED ALK-POSITIVE NON-SMALL CELL LUNG CANCER

A phase 3 study to demonstrate whether lorlatinib given as monotherapy is superior to crizotinib alone in prolonging the progression-free survival in advanced ALK-positive NSCLC patients who are treatment naïve and to compare lorlatinib to crizotinib with respect to overall survival in the same population

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Lorlatinib; Drug: Crizotinib

• Study Type: Interventional
• Enrollment (Actual): 296
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, C1019ABS
    • Centro Medico Austral
  • Buenos Aires
    • Pergamino, Buenos Aires, Argentina, B2700CPM
      • Centro de Investigacion Pergamino SA
• Australia
  • Victoria
    • Bendigo, Victoria, Australia, 3550
      • Bendigo Day Surgery Collection Centre and Laboratory
    • Bendigo, Victoria, Australia, 3550
      • Bendigo Medical Imaging, Bendigo Hospital
    • Bendigo, Victoria, Australia, 3550
      • Melbourne Pathology
    • Melbourne, Victoria, Australia, 3000
      • Peter Maccallum Cancer Centre
• Belgium
  • Charleroi, Belgium, 6000
    • Grand Hôpital de Charleroi - Site Notre Dame
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Guangzhou, China, 510000
    • Guangdong General Hospital
  • Beijing
    • Beijing, Beijing, China, 100071
      • The Affiliated Hospital of Military Medical Sciences
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Provincial Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Chest Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310009
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310003
      • Department of Respiratory,the First Affiliated Hospital of College of Medicine, Zhejiang University
• Czechia
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc, Klinika plicnich nemoci a tuberkulozy
  • Praha 2, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze
• France
  • Chevilly Larue, France, 94550
    • Hopital de Chevilly Larue
  • Le Mans, France, 72000
    • Centre Hospitalier du Mans
  • Marseille cedex 09, France, 13273
    • Institut Paoli-Calmettes
  • Marseille cedex 20, France, 13915
    • Département d'Imagerie Médicale
  • Marseille cedex 20, France, 13915
    • Hopital Nord
  • Marseille cedex 20, France, 13915
    • Service Ophtalmologie
  • Paris, France, 75018
    • Groupe Hospitalier Bichat Claude Bernard, AP-HP
  • Rennes cedex 9, France, 35033
    • CHU de Rennes Hopital Pontchaillou
  • Rennes cedex 9, France, 35033
    • CHU de Rennes, Hopital Pontchaillou
  • Suresnes, France, 92150
    • Hopital Foch
  • Toulouse Cedex 9, France, 31059
    • Hopital Larrey
  • Toulouse cedex 9, France, 31059
    • Hopital Pierre Paul Riquet
  • Villejuif, France, 94805
    • Institut Gustave Roussy
  • Villejuif, France, 94805
    • Department d'imagerie medicale
  • Aquitaine
    • Pessac, Aquitaine, France, 33604
      • Hopital Haut-Léveque-Centre François Magendie
• Germany
  • Dresden, Germany, 01309
    • Uberortliche Radiologische Gemeinschaftspraxis Dr. med. Marc Amler
  • Dresden, Germany, D-01307
    • Technische Universitat Dresden , Medizinische Fakultat Carl Gustav Carus
  • Heidelberg, Germany, D-69126
    • Thoraxklinik Heidelberg gGmbH
  • Heidelberg, Germany, D-69126
    • Universitätsklinikum Heidelberg
  • Homburg - Saar, Germany, 66421
    • Universitätsklinikum des Saarlandes, Innere Medizin V
  • Homburg - Saar, Germany, 66421
    • Universitätsklinikum des Saarlandes
  • Regensburg, Germany, 93053
    • Universitatsklinikum Regensburg, Institut fur Rontgendiagnostik
  • Regensburg, Germany, 93053
    • Universitatsklinikum Regensburg, Klinik und Poliklinik fur Innere Medizin II
• Hong Kong
  • Hong Kong, Hong Kong
    • Tuen Mun Hospital
  • Hong Kong, Hong Kong
    • The University of Hong Kong, Department of Clinical Oncology
  • Hong Kong, Hong Kong
    • The University of Hong Kong, Department of Medicine
• India
  • Haryana
    • Gurugram, Haryana, India, 122001
      • Artemis Hospital
  • Karnataka
    • Bangalore, Karnataka, India, 560017
      • Manipal Hospital
    • Bangalore, Karnataka, India, 560072
      • Srinivasam Cancer Care Multispeciality Hospitals India Pvt Ltd
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Sahyadri Clinical Research and Development Centre
    • Pune, Maharashtra, India, 411004
      • Sahyadri Specialty Hospital
• Italy
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Dei Colli Ospedale Monaldi
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori di Napoli
  • Ravenna, Italy, 48121
    • Ausl della Romagna- Ravenna
  • CT
    • Catania, CT, Italy, 95123
      • AOU Policlinico Vittorio Emanuele-P.O.G. Rodolico
  • MB
    • Monza, MB, Italy, 20900
      • ASST Monza - A.O. San Gerardo
  • MI
    • Milano, MI, Italy, 20132
      • IRCCS Ospedale San Raffaele
    • Milano, MI, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Milano, MI, Italy, 20141
      • Istituto Europeo di Oncologia
    • Rozzano, MI, Italy, 20089
      • Istituto Clinico Humanitas
  • PG
    • Perugia, PG, Italy, 06132
      • Azienda Ospedaliera di Perugia - Ospedale S. M. Misericordia
  • PN
    • Pordenone, PN, Italy, 33081
      • Centro di Riferimento Oncologico-IRCCS
  • PR
    • Parma, PR, Italy, 43126
      • Azienda Ospedaliero-Universitaria di Parma
  • RM
    • Roma, RM, Italy, 00144
      • Istituto Nazionale Tumori Regina Elena
    • Roma, RM, Italy, 00152
      • Az.Osp.San Camillo-Forlanini
• Japan
  • Koto-ku, Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Osaka, Japan, 534-0021
    • Osaka City General Hospital
  • Tokushima, Japan, 770-8503
    • Tokushima University Hospital
  • Wakayama, Japan, 641-8509
    • Wakayama Medical University Department of Pulmonary Medicine and Oncology
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital
    • Nagoya, Aichi, Japan, 464-8681
      • Aichi cancer center central hospital
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8641
      • Kanazawa University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center
  • Miyagi
    • Sendai, Miyagi, Japan, 980-0873
      • Sendai Kousei Hospital
  • Osaka
    • Osaka-shi, Osaka, Japan, 541-8567
      • Osaka International Cancer Institute
    • Osakasayama, Osaka, Japan, 589-8511
      • Kindai University Hospital
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center
  • Tokyo
    • Chuo-Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-0241
      • National Hospital Organization, Yamaguchi-Ube Medical Center
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 03722
    • Division of Medical Oncology, Severance Hospital, Yonsei University Health System
  • Ulsan, Korea, Republic of, 44033
    • Ulsan University Hospital
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, Korea, Republic of, 16247
      • The Catholic University of Korea, St. Vincents Hospital
• Mexico
  • Aguascalientes, Mexico, 20230
    • Médicos Especialistas en Cancer S.C. / San Peregrino.
  • Distrito Federal, Mexico, 14080
    • Instituto Nacional de Cancerologia
  • Distrito Federal, Mexico, 14080
    • Instituto Nacional De Enfermedades Respiratorias Ismael Cosio Villegas
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
• Poland
  • Gdansk, Poland, 80-214
    • Klinika Onkologii i Radioterapii Uniwersyteckie Centrum Kliniczne
  • Poznan, Poland, 60-693
    • Med-Polonia Sp. z o.o.
  • Szczecin, Poland, 70-784
    • Centrum Medyczne Dom Lekarski S.A.
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie-Panstwowy Instytut Badawczy
• Russian Federation
  • Kursk, Russian Federation, 305 035
    • RBHI Kursk Regional Clinical Oncology Dispensary
  • Moscow, Russian Federation, 115478
    • FSBI "N.N.Blokhin Medical Research Center of Oncology"
  • Kursk Region
    • Kislino, Ryshkovsky Rural Council, Kursk Region, Russian Federation, 305 524
      • RBHI Kursk Regional Clinical Oncology Dispensary
  • OMSK Region
    • Omsk, OMSK Region, Russian Federation, 644013
      • Budgetary Healthcare Institution Omsk Region "Clinical Oncological Dispensary"
  • Saint-petersburg
    • Pesochniy Poselok, Saint-petersburg, Russian Federation, 197758
      • LEC at SBIH "Saint-Petersburg Clinical Research Practical Center of specialized types of
    • Pushkin, Saint-petersburg, Russian Federation, 196603
      • Private medical institution "Euromedservice"
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 188770
    • Raffles Hospital
• Spain
  • A Coruna, Spain, 15006
    • Hospital Teresa Herrera C.H.U.A.C.
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Girona, Spain, 17007
    • Institut Català D'Oncologia Girona
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28040
    • Hospital Universitario Fundación Jiménez Díaz
  • Valencia, Spain, 46026
    • Hospital Universitario La Fe
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Institut Catala d'Oncologia l'Hospitalet
  • Canarias
    • Las Palmas de Gran Canaria, Canarias, Spain, 35016
      • Hospital Universitario Insular de Gran Canaria
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro Majadahonda
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Complejo Hospitalario de Navarra
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Chang Gung Memorial Hospital - Kaohsiung Branch
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taichung, Taiwan, 402
    • Chung Shan Medical University Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taiwan ROC
    • Taipei, Taiwan ROC, Taiwan, 10002
      • National Taiwan University Hospital
• Turkey
  • Adana, Turkey, 01330
    • Cukurova University Medical Faculty
  • Istanbul, Turkey, 34093
    • Istanbul University Oncology Institute
  • Istanbul, Turkey, 34899
    • Marmara Univ Pendik Training and Research Hospital
  • Izmir, Turkey, 35100
    • Ege University Medical Faculty
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Suffolk
    • Ipswich, Suffolk, United Kingdom, IP4 5PD
      • The Ipswich Hospital NHS Trust
  • WEST Midlands
    • Birmingham, WEST Midlands, United Kingdom, B9 5SS
      • Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
• United States
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Florida Cancer Specialists
    • Brandon, Florida, United States, 33511
      • Florida Cancer Specialists
    • Clearwater, Florida, United States, 33761
      • Florida Cancer Specialists
    • Gainesville, Florida, United States, 32605
      • Florida Cancer Specialists
    • Largo, Florida, United States, 33770
      • Florida Cancer Specialists
    • Lecanto, Florida, United States, 34461
      • Florida Cancer Specialists
    • Orange City, Florida, United States, 32763
      • Florida Cancer Specialists
    • Orlando, Florida, United States, 32806
      • Florida Cancer Specialists
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists
    • Spring Hill, Florida, United States, 34608
      • Florida Cancer Specialists
    • Tampa, Florida, United States, 33607
      • Florida Cancer Specialists
    • Tavares, Florida, United States, 32778
      • Florida Cancer Specialists
    • The Villages, Florida, United States, 32159
      • Florida Cancer Specialists
    • Winter Park, Florida, United States, 32792
      • Florida Cancer Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Eye and Ear Infirmary
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston Inc
    • Boston, Massachusetts, United States, 02215
      • The William P. Beetham Eye Institute, Joslin Diabetes Center
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Cancer Center Pharmacy
  • Tennessee
    • Dickson, Tennessee, United States, 37055
      • Tennessee Oncology, PLLC
    • Franklin, Tennessee, United States, 37067
      • Tennessee Oncology, PLLC
    • Gallatin, Tennessee, United States, 37066
      • Tennessee Oncology, PLLC
    • Hermitage, Tennessee, United States, 37076
      • Tennessee Oncology, PLLC
    • Lebanon, Tennessee, United States, 37090
      • Tennessee Oncology, PLLC
    • Murfreesboro, Tennessee, United States, 37129
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37205
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37207
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37211
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute.
    • Shelbyville, Tennessee, United States, 37160
      • Tennessee Oncology, PLLC
    • Smyrna, Tennessee, United States, 37167
      • Tennessee Oncology, PLLC
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical 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 locally advanced or metastatic ALK-positive NSCLC; at least 1 extracranial measurable target lesion not previously irradiated. CNS metastases allowed if asymptomatic and not currently requiring corticosteroid treatment.
• Availability of an archival FFPE tissue specimen.
• No prior systemic NSCLC treatment.
• ECOG PS 0, 1, or 2.
• Age ≥18 years .
• Adequate Bone Marrow, Liver, Renal, Pancreatic Function
• Negative pregnancy test for females of childbearing potential

Exclusion Criteria:

• Spinal cord compression unless good pain control attained
• Major surgery within 4 weeks prior to randomization.
• Radiation therapy within 2 weeks prior to randomization, including stereotactic or partial brain irradiation. Whole brain irradiation within 4 weeks prior to randomization
• Active bacterial, fungal, or viral infection
• Clinically significant cardiovascular disease, active or within 3 months prior to enrollment. Ongoing cardiac dysrhythmias, uncontrolled atrial fibrillation, bradycardia or congenital long QT syndrome
• Predisposing characteristics for acute pancreatitis in the last month prior to randomization.
• History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease
• Active malignancy (other than NSCLC, non melanoma skin cancer, in situ cervical cancer, papillary thyroid cancer, LCIS/DCIS of the breast, or localized prostate cancer) within the last 3 years prior to randomization.

• Concurrent use of any of the following food or drugs within 12 days prior to the first dose of lorlatinib or crizotinib.

  1. known strong CYP3A inhibitors .
  2. known strong CYP3A inducers
  3. known P gp substrates with a narrow therapeutic index
• Concurrent use of CYP3A substrates with narrow therapeutic indices within 12 days prior to the first dose of lorlatinib or crizotinib.
• Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or interfere with the interpretation of study results
• Investigational site staff members directly involved in the conduct of the study and their family members, or Pfizer employees, including their family members, directly involved in the conduct of the study.
• Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation.

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: Lorlatinib; Lorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously	Drug: Lorlatinib; ALK-positive NSCL treatment; Other Names: PF-06463922
Active Comparator: Crizotinib; Crizotinib single agent, 250 mg (1 x 250) oral capsules, BID, continuously	Drug: Crizotinib; ALK-positive NSCL treatment; Other Names: Xalkori

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment	PFS was defined as the time from randomization to the date of the first documentation of progressive disease as assessed by the independent radiologist or death due to any cause, whichever occurred first. PFS (in months) was calculated as (date of event or censoring-randomization+1)/30.4375. Progressive disease is defined per RECIST version 1.1, as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.	From time of Study Start up to 33 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to the date of death due to any cause. OS (in months) was calculated as (date of death or censoring - start date +1)/30.4375. Participants last known to be alive were censored at date of last contact.	From time of Study Start up to 33 months
Progression-Free Survival (PFS) Based on Investigator's Assessment	PFS was defined as the time from randomization to the date of the first documentation of progressive disease as assessed by investigator or death due to any cause, whichever occurred first. PFS (in months) was calculated as (date of event or censoring-randomization+1)/30.4375. Progressive disease is defined per RECIST version 1.1, as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.	From time of Study Start up to 33 months
Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on BICR Assessment	ORR was the percentage of participants with objective response of complete response (CR) or partial response (PR) according to RECIST version 1.1 recorded from randomization until disease progression or start of new anti-cancer therapy. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). PR was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	From time of Study Start up to 33 months
Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on Investigator's Assessment	ORR was the percentage of participants with objective response of complete response (CR) or partial response (PR) according to RECIST version 1.1 recorded from randomization until disease progression or start of new anti-cancer therapy. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). PR was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	From time of Study Start up to 33 months
Intracranial Objective Response Rate (IC-ORR) - Percentage of Participants With Intracranial Objective Response (IC-OR) Based on BICR Assessment	IC-ORR was the percentage of participant with intracranial objective response of complete response (CR) or partial response (PR) based on intracranial disease in the subset of participants with at least 1 intracranial lesion per RECIST version 1.1 (modified) recorded from randomization until disease progression or start of new anti-cancer therapy. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). PR was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	From time of Study Start up to 33 months
Intracranial Time to Progression (IC-TTP) Based on BICR Assessment	IC-TTP based on BICR assessment was defined as the time from date of randomization to the date of the first documentation of progression of intracranial disease, based on either new brain metastases or progression of existing brain metastases.	From time of Study Start up to 33 months
Duration of Response (DR) Based on BICR Assessment	DR was defined, for participants with a confirmed objective response (OR) of complete response (CR) or partial response (PR) per RECIST version 1.1, as the time from the first documentation of OR to the first documentation of progressive disease (PD) or death due to any cause, whichever occurred first. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). PR was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.	From time of Study Start up to 33 months
Intracranial Duration of Response (IC-DR) Based on BICR Assessment	IC-DR was defined, for participants with a confirmed intracranial objective response (OR) of complete response (CR) or partial response (PR) per RECIST version 1.1, as the time from the first documentation of intracranial OR to the first documentation of intracranial progressive disease (PD) or death due to any cause, whichever occurred first. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). PR was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.	From time of Study Start up to 33 months
Time to Tumor Response (TTR) Based on BICR Assessment	TTR based on BICR assessment was defined, for participants with a confirmed objective response, as the time from the date of randomization to the first documentation of objective response (complete response or partial response) which was subsequently confirmed. Complete response was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). Partial response was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	From time of Study Start up to 33 months
Intracranial Time to Tumor Response (IC-TTR) Based on BICR Assessment	IC-TTR was defined, for participants with a confirmed intracranial objective response, as the time from the date of randomization to the first documentation of intracranial objective response (complete response or partial response) which was subsequently confirmed. Complete response was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). Partial response was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	From time of Study Start up to 33 months
PFS2 Based on Investigator's Assessment	PFS2 was defined as the time from randomization to the date of progression of disease on first subsequent systemic anti-cancer therapy, or death from any cause, whichever occurred first	From time of Study Start up to 45 months
Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related)	An AE was an untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death, life-threatening experience, initial or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. All AEs in the table below were treatment-emergent AEs. Grade 3 and 4 AEs in the table below indicated severe AE and life-threatening consequences respectively; Grade 5 indicated death due to AE. Treatment-related AEs were determined by investigators.	From time of Study Start up to 33 months
Number of Participants With Changes in Hematology Laboratory Parameters From Baseline Maximum NCI-CTCAE Grade Lower Than 3 to Postbaseline Maximum Grade 3 or Grade 4	Laboratory test results were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grades 1 and 2 indicate mild and moderate AE, respectively; Grades 3 and 4 indicate severe AE and life-threatening consequences respectively; Grade 5 indicates death due to AE. Participants with laboratory test abnormalities were summarized according to the worst grade for each laboratory test result. All participants meeting the postbaseline grade criteria in the table below had baseline maximum grades lower than 3.	From Baseline up to 33 months
Number of Participants With Changes in Chemistry Laboratory Parameters From Baseline Maximum NCI-CTCAE Grade Lower Than 3 to Postbaseline Maximum Grade 3 or Grade 4	Laboratory test results were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grades 1 and 2 indicate mild and moderate AE, respectively; Grades 3 and 4 indicate severe AE and life-threatening consequences respectively; Grade 5 indicates death due to AE. Participants with laboratory test abnormalities were summarized according to the worst grade for each laboratory test result. All participants meeting the postbaseline grade criteria in the table below had baseline maximum grades lower than 3.	From Baseline up to 33 months
Number of Participants With Changes in Lipid Laboratory Parameters From Baseline Maximum NCI-CTCAE Grade Lower Than 3 to Postbaseline Maximum Grade 3 or Grade 4	Laboratory test results were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grades 1 and 2 indicate mild and moderate AE, respectively; Grades 3 and 4 indicate severe AE and life-threatening consequences respectively; Grade 5 indicates death due to AE. Participants with laboratory test abnormalities were summarized according to the worst grade for each laboratory test result. All participants meeting the postbaseline grade criteria in the table below had baseline maximum grades lower than 3.	From Baseline up to 33 months
Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria	Vital signs data included pulse, systolic blood pressure, and diastolic blood pressure. Measurements were only provided once per timepoint. If multiple assessments were provided per timepoint, the maximum value were used for reporting. The pre-defined criteria of vital sign and body weight data were as follows: maximum pulse rate >120 beats per minute (bpm); minimum pulse rate <50 bpm; maximum increase in pulse rate ≥30 bpm; maximum decrease in pulse rate ≥30 bpm; increase in systolic blood Pressure ≥40 mmHg; decrease in systolic blood pressure ≥40 mmHg; decrease in systolic blood pressure ≥60 mmHg; increase in diastolic blood pressure ≥20 mmHg; decrease in diastolic blood pressure ≥20 mmHg; decrease in diastolic blood pressure ≥40 mmHg; increase in body weight ≥10%; increase in body weight ≥20%; decrease in body weight ≥10%.	From Baseline up to 33 months
Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria	Baseline was defined as the last assessment performed on or prior to date of the first dose of study treatment. Triplicate ECGs were collected in the study and the average of the replicate assessments were used for summary analysis. The pre-defined criteria of ECG data were as follows: change from baseline in QTcF ≥60 msec, ≥30 msec but <60 msec, <30 msec; change from baseline in QTcB ≥60 msec, ≥30 msec but <60 msec, <30 msec; PR change ≥50% if absolute baseline value was <200 msec; PR change ≥25% if absolute baseline value was ≥200 msec; QRS change ≥50% if absolute baseline value was <100 msec; QRS change ≥25% if absolute baseline value was ≥100 msec.	From Baseline up to 33 months
Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Points in Left Ventricular Ejection Fraction (LVEF) Percentage	In this outcome measure, baseline was defined as the last assessment on or prior to the date of the first dose of study treatment. Decrease from baseline was an absolute difference between baseline and observed value.	From Baseline up to 33 months
Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time	BDI-II (Mood Assessment) is a 21 item self-reported scale, with each item rated by participants on a 4-point scale (ranging from 0-3). The scale includes items capturing mood, (loss of pleasure, sadness, and irritability), suicidal ideation, and cognitive signs (punitive thoughts, self-criticism, self-dislike pessimism, poor concentration) as well as somatic signs (appetite, sleep, fatigue, libido). Scores were obtained by adding up the total points from the series of answers. The total score ranged from 0 to 63, with higher total scores indicating more severe depressive symptoms. The standardized cutoffs are as follows: 0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; 29-63: severe depression.	Baseline, Cycle 2 Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C8D1, C10D1, C12D1, C14D1, C16D1, C18D1, C20D1, C22D1, C24D1, C26D1, C28D1, C30D1, C32D1, C34D1, C36D1, C38D1 and End of Treatment
Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time	Suicidal ideation and behaviors were assessed by the Columbia Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a unique, simple and short method of assessing both behavior and ideation that tracks all suicidal events and provides a summary of suicidality. It assesses the lethality of attempts and other features of ideation (frequency, duration, controllability, reasons for ideation, and deterrents), all of which are significantly predictive of completed suicide.	Baseline, Cycle 2 Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C8D1, C10D1, C12D1, C14D1, C16D1, C18D1, C20D1, C22D1, C24D1, C26D1, C28D1, C30D1, C32D1, C34D1, C36D1, C38D1 and End of Treatment
Change From Baseline in Global Quality of Life (QOL), Functional Scales and Symptoms Scales as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) During Overall Treatment	The EORTC QLQ C30 consists of 30 questions and includes 5 functional scales (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale; 3 symptom scales (fatigue, pain, nausea and vomiting); and 6 single items that assess additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and financial impact. All scales and single item measures range in score from 0 to 100. Higher scores on the functional scales represent higher levels of functioning. Higher scores on the global health status/quality of life scale represent higher health status/quality of life. Higher scores on symptom scales/items represent a greater presence of symptoms.	From Baseline up to Cycle 38 Day 1
Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment	The EORTC QLQ LC13 consists of 13 questions and includes 1 multi-item scale and 9 single items assessing symptoms (dyspnea, cough, haemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication use. The scale scores rang from 0 to 100, with higher scores indicating higher ("worse") level of symptoms.	From Baseline up to Cycle 38 Day 1
Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time	The EuroQol EQ-5D-5L is a participant-completed questionnaire designed to assess health status. There are 2 components to the EuroQol EQ-5D-5L: a descriptive system in which individuals rate their level of problems (none, slight, moderate, severe, extreme/unable) in 5 areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a VAS. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) and higher scores indicate better health state.	Baseline, Day 1 of all cycles from Cycle 2 to Cycle 38, and End of Treatment
Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time	The EuroQol EQ-5D-5L is a participant-completed questionnaire designed to assess health status. There are 2 components to the EuroQol EQ-5D-5L: a descriptive system in which individuals rate their level of problems (none, slight, moderate, severe, extreme/unable) in 5 areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a VAS in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable). EQ-5D summary index is obtained with a formula that weights each level of the 5 dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health).	Baseline, Day 1 of all cycles from Cycle 2 to Cycle 38, and End of Treatment
Time to Deterioration (TTD) in Participant Reported Pain in Chest, Dyspnea, or Cough From QLQ-LC13	The EORTC QLQ LC13 consists of 13 questions and includes 1 multi-item scale and 9 single items assessing symptoms (dyspnea, cough, haemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication use. The scale scores rang from 0 to 100, with higher scores indicating higher ("worse") level of symptoms. TTD in pain in chest, dyspnea, or cough was defined as the time from randomization to the first time the participant's score showed a 10 point or greater increase after baseline in any of the 3 symptoms. TTD in months was calculated as (date of deterioration or censoring - randomization date +1)/30.4375.	From Baseline up to 33 months
Number of Participant With ALK Domain Mutation in Plasma Circulating Nucleic Acid (CNA) Analysis at Screening, Cycle 2 Day 1 and Cycle 7 Day 1	The analysis of anaplastic lymphoma kinase (ALK) domain mutation in plasma CNA was performed by next-generation sequencing (NGS) and the number of participants with one or more ALK mutations at Screening, Cycle 2 Day 1 and Cycle 7 Day 1 is presented here.	at Screening, Cycle 2 Day 1 and Cycle 7 Day 1
Number of Participant With ALK Fusion Variant in Plasma Circulating Nucleic Acid (CNA) Analysis at Screening, Cycle 2 Day 1 and Cycle 7 Day 1	The analysis of ALK fusion variant in plasma CNA was performed by NGS and the number of participants with fusion variants at Screening, Cycle 2 Day 1 and Cycle 7 Day 1 is presented here. In the table below, EML4-ALK is the abbreviation of echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase.	at Screening, Cycle 2 Day 1 and Cycle 7 Day 1

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

• 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.
• Solomon BJ, Bauer TM, Ignatius Ou SH, Liu G, Hayashi H, Bearz A, Penkov K, Wu YL, Arrieta O, Jassem J, Calella AM, Peltz G, Polli A, Thurm H, Mok T. Post Hoc Analysis of Lorlatinib Intracranial Efficacy and Safety in Patients With ALK-Positive Advanced Non-Small-Cell Lung Cancer From the Phase III CROWN Study. J Clin Oncol. 2022 Nov 1;40(31):3593-3602. doi: 10.1200/JCO.21.02278. Epub 2022 May 23.
• Solomon BJ, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, Thurm H, Calella AM, Peltz G, Shaw AT. Plain language summary of the CROWN study comparing lorlatinib with crizotinib for people with untreated non-small cell lung cancer. Future Oncol. 2021 Dec 1;17(34):4649-4656. doi: 10.2217/fon-2021-0904. Epub 2021 Sep 29.
• Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, Thurm H, Calella AM, Peltz G, Solomon BJ; CROWN Trial Investigators. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2020 Nov 19;383(21):2018-2029. doi: 10.1056/NEJMoa2027187.
• Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599. doi: 10.1016/S1470-2045(17)30680-0. Epub 2017 Oct 23.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2017
• Primary Completion (Actual): March 20, 2020
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 20, 2017
• First Submitted That Met QC Criteria: February 9, 2017
• First Posted (Actual): February 14, 2017

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: ALK; anaplastic lymphoma kinase; Non-Small-Cell Lung cancer; NSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Crizotinib
• Other Study ID Numbers: B7461006; 2016-003315-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No