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

• ClinicalTrials.gov Identifier: NCT03052608
• Recruitment Status: Active, not recruiting
• First Posted: February 14, 2017
• Results First Posted: April 1, 2021
• Last Update Posted: February 20, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Lorlatinib; Drug: Crizotinib	Phase 3

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Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 296 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 27, 2017
• Actual Primary Completion Date: March 20, 2020
• Estimated Study Completion Date: December 31, 2028

Arms and Interventions

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 Name: PF-06463922
Active Comparator: Crizotinib; Crizotinib single agent, 250 mg (1 x 250) oral capsules, BID, continuously	Drug: Crizotinib; ALK-positive NSCL treatment; Other Name: Xalkori

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment [ Time Frame: From time of Study Start up to 33 months ]
   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.

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: From time of Study Start up to 33 months ]
   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.
2. Progression-Free Survival (PFS) Based on Investigator's Assessment [ Time Frame: From time of Study Start up to 33 months ]
   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.
3. Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on BICR Assessment [ Time Frame: From time of Study Start up to 33 months ]
   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.
4. Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on Investigator's Assessment [ Time Frame: From time of Study Start up to 33 months ]
   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.
5. Intracranial Objective Response Rate (IC-ORR) - Percentage of Participants With Intracranial Objective Response (IC-OR) Based on BICR Assessment [ Time Frame: From time of Study Start up to 33 months ]
   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.
6. Intracranial Time to Progression (IC-TTP) Based on BICR Assessment [ Time Frame: From time of Study Start up to 33 months ]
   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.
7. Duration of Response (DR) Based on BICR Assessment [ Time Frame: From time of Study Start up to 33 months ]
   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.
8. Intracranial Duration of Response (IC-DR) Based on BICR Assessment [ Time Frame: From time of Study Start up to 33 months ]
   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.
9. Time to Tumor Response (TTR) Based on BICR Assessment [ Time Frame: From time of Study Start up to 33 months ]
   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.
10. Intracranial Time to Tumor Response (IC-TTR) Based on BICR Assessment [ Time Frame: From time of Study Start up to 33 months ]
    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.
11. PFS2 Based on Investigator's Assessment [ Time Frame: From time of Study Start up to 45 months ]
    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
12. Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) [ Time Frame: From time of Study Start up to 33 months ]
    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.
13. 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 [ Time Frame: From Baseline up to 33 months ]
    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.
14. 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 [ Time Frame: From Baseline up to 33 months ]
    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.
15. 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 [ Time Frame: From Baseline up to 33 months ]
    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.
16. Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria [ Time Frame: From Baseline up to 33 months ]
    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%.
17. Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria [ Time Frame: From Baseline up to 33 months ]
    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.
18. Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Points in Left Ventricular Ejection Fraction (LVEF) Percentage [ Time Frame: From Baseline up to 33 months ]
    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.
19. Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time [ Time Frame: 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 ]
    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.
20. Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time [ Time Frame: 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 ]
    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.
21. 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 [ Time Frame: From Baseline up to Cycle 38 Day 1 ]
    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.
22. Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment [ Time Frame: From Baseline up to Cycle 38 Day 1 ]
    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.
23. Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time [ Time Frame: Baseline, Day 1 of all cycles from Cycle 2 to Cycle 38, and End of Treatment ]
    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.
24. Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time [ Time Frame: Baseline, Day 1 of all cycles from Cycle 2 to Cycle 38, and End of Treatment ]
    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).
25. Time to Deterioration (TTD) in Participant Reported Pain in Chest, Dyspnea, or Cough From QLQ-LC13 [ Time Frame: From Baseline up to 33 months ]
    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.
26. 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 [ Time Frame: 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.
27. 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 [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Florida

Florida Cancer Specialists

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

United States, Massachusetts

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States, 02114

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Ophthalmic Consultants of Boston Inc

Boston, Massachusetts, United States, 02114

The William P. Beetham Eye Institute, Joslin Diabetes Center

Boston, Massachusetts, United States, 02215

United States, New York

University of Rochester Cancer Center Pharmacy

Rochester, New York, United States, 14642

University of Rochester Medical Center

Rochester, New York, United States, 14642

United States, Tennessee

Tennessee Oncology, PLLC

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

The Sarah Cannon Research Institute.

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

Shelbyville, Tennessee, United States, 37160

Tennessee Oncology, PLLC

Smyrna, Tennessee, United States, 37167

United States, Washington

University of Washington Medical Center

Seattle, Washington, United States, 98195

Argentina

Centro de Investigacion Pergamino SA

Pergamino, Buenos Aires, Argentina, B2700CPM

Centro Medico Austral

Caba, Argentina, C1019ABS

Australia, Victoria

Bendigo Day Surgery Collection Centre and Laboratory

Bendigo, Victoria, Australia, 3550

Bendigo Medical Imaging, Bendigo Hospital

Bendigo, Victoria, Australia, 3550

Melbourne Pathology

Bendigo, Victoria, Australia, 3550

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia, 3000

Belgium

Grand Hopital de Charleroi - Site Notre Dame

Charleroi, Belgium, 6000

Canada, Ontario

Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

McGill University Health Centre

Montreal, Quebec, Canada, H4A 3J1

China, Beijing

The Affiliated Hospital of Military Medical Sciences

Beijing, Beijing, China, 100071

China, Jilin

Jilin Provincial Cancer Hospital

Changchun, Jilin, China, 130012

China, Shanghai

Shanghai Chest Hospital

Shanghai, Shanghai, China, 200030

China, Zhejiang

Department of Respiratory,the First Affiliated Hospital of College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China, 310003

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China, 310009

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China, 310022

China

Beijing Cancer Hospital

Beijing, China, 100142

Guangdong General Hospital

Guangzhou, China, 510000

Czechia

Fakultni nemocnice Olomouc, Klinika plicnich nemoci a tuberkulozy

Olomouc, Czechia, 779 00

Vseobecna fakultni nemocnice v Praze

Praha 2, Czechia, 128 08

France

Hopital Haut-Léveque-Centre François Magendie

Pessac, Aquitaine, France, 33604

Hopital de Chevilly Larue

Chevilly Larue, France, 94550

Centre Hospitalier du Mans

Le Mans, France, 72000

Institut Paoli-Calmettes

Marseille cedex 09, France, 13273

Département d'Imagerie Médicale

Marseille cedex 20, France, 13915

Hôpital Nord

Marseille cedex 20, France, 13915

Service Ophtalmologie

Marseille cedex 20, France, 13915

Groupe Hospitalier Bichat Claude Bernard, AP-HP

Paris, France, 75018

CHU de Rennes Hopital Pontchaillou

Rennes cedex 9, France, 35033

CHU de Rennes, Hopital Pontchaillou

Rennes cedex 9, France, 35033

Hopital Foch

Suresnes, France, 92150

Hopital Larrey

Toulouse Cedex 9, France, 31059

Hopital Pierre Paul Riquet

Toulouse cedex 9, France, 31059

Hôpital Larrey

Toulouse Cedex 9, France, 31059

Department d'imagerie medicale

Villejuif, France, 94805

Institut Gustave Roussy

Villejuif, France, 94805

Germany

Uberortliche Radiologische Gemeinschaftspraxis Dr. med. Marc Amler

Dresden, Germany, 01309

Technische Universitat Dresden , Medizinische Fakultat Carl Gustav Carus

Dresden, Germany, D-01307

Thoraxklinik Heidelberg gGmbH

Heidelberg, Germany, D-69126

Universitatsklinikum Heidelberg

Heidelberg, Germany, D-69126

Universitätsklinikum des Saarlandes, Innere Medizin V

Homburg - Saar, Germany, 66421

Universitätsklinikum des Saarlandes

Homburg - Saar, Germany, 66421

Universitatsklinikum Regensburg, Institut fur Rontgendiagnostik

Regensburg, Germany, 93053

Universitatsklinikum Regensburg, Klinik und Poliklinik fur Innere Medizin II

Regensburg, Germany, 93053

Hong Kong

The University of Hong Kong, Department of Clinical Oncology

Hong Kong, Hong Kong

The University of Hong Kong, Department of Medicine

Hong Kong, Hong Kong

Tuen Mun Hospital

Hong Kong, Hong Kong

India

Artemis Hospital

Gurugram, Haryana, India, 122001

Manipal Hospital

Bangalore, Karnataka, India, 560017

Srinivasam Cancer Care Multispeciality Hospitals India Pvt Ltd

Bangalore, Karnataka, India, 560072

Sahyadri Clinical Research and Development Centre

Pune, Maharashtra, India, 411004

Sahyadri Specialty Hospital

Pune, Maharashtra, India, 411004

Italy

AOU Policlinico Vittorio Emanuele-P.O.G. Rodolico

Catania, CT, Italy, 95123

ASST Monza - A.O. San Gerardo

Monza, MB, Italy, 20900

IRCCS Ospedale San Raffaele

Milano, MI, Italy, 20132

Fondazione IRCCS Istituto Nazionale dei Tumori

Milano, MI, Italy, 20133

Istituto Europeo di Oncologia

Milano, MI, Italy, 20141

Istituto Clinico Humanitas

Rozzano, MI, Italy, 20089

Azienda Ospedaliera di Perugia - Ospedale S. M. Misericordia

Perugia, PG, Italy, 06132

Centro di Riferimento Oncologico-IRCCS

Pordenone, PN, Italy, 33081

Azienda Ospedaliero-Universitaria di Parma

Parma, PR, Italy, 43126

Istituto Nazionale Tumori Regina Elena

Roma, RM, Italy, 00144

Az.Osp.San Camillo-Forlanini

Roma, RM, Italy, 00152

Azienda Ospedaliera Dei Colli Ospedale Monaldi

Napoli, Italy, 80131

Istituto Nazionale Tumori di Napoli

Napoli, Italy, 80131

Ausl della Romagna- Ravenna

Ravenna, Italy, 48121

Japan

Aichi cancer center central hospital

Nagoya, Aichi, Japan, 464-8681

Nagoya University Hospital

Nagoya, Aichi, Japan, 466-8560

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, Japan, 791-0280

Kurume University Hospital

Kurume, Fukuoka, Japan, 830-0011

National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido, Japan, 003-0804

Kanazawa University Hospital

Kanazawa, Ishikawa, Japan, 920-8641

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan, 241-8515

Sendai Kousei Hospital

Sendai, Miyagi, Japan, 980-0873

Osaka International Cancer Institute

Osaka-shi, Osaka, Japan, 541-8567

Kindai University Hospital

Osakasayama, Osaka, Japan, 589-8511

Shizuoka Cancer Center

Sunto-gun, Shizuoka, Japan, 411-8777

National Cancer Center Hospital

Chuo-Ku, Tokyo, Japan, 104-0045

National Hospital Organization, Yamaguchi-Ube Medical Center

Ube, Yamaguchi, Japan, 755-0241

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, Japan, 135-8550

Niigata Cancer Center Hospital

Niigata, Japan, 951-8566

Okayama University Hospital

Okayama, Japan, 700-8558

Osaka City General Hospital

Osaka, Japan, 534-0021

Tokushima University Hospital

Tokushima, Japan, 770-8503

Wakayama Medical University Department of Pulmonary Medicine and Oncology

Wakayama, Japan, 641-8509

Korea, Republic of

The Catholic University of Korea, St. Vincents Hospital

Suwon, Gyeonggi-do, Korea, Republic of, 16247

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Division of Medical Oncology, Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 03722

Asan Medical Center

Seoul, Korea, Republic of, 05505

Ulsan University Hospital

Ulsan, Korea, Republic of, 44033

Mexico

Médicos Especialistas en Cancer S.C. / San Peregrino.

Aguascalientes, Mexico, 20230

Instituto Nacional de Cancerologia

Distrito Federal, Mexico, 14080

Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Distrito Federal, Mexico, 14080

Netherlands

University Medical Center Groningen

Groningen, Netherlands, 9713 GZ

Poland

Klinika Onkologii i Radioterapii Uniwersyteckie Centrum Kliniczne

Gdansk, Poland, 80-214

Med-Polonia Sp. z o.o.

Poznan, Poland, 60-693

Centrum Medyczne Dom Lekarski S.A.

Szczecin, Poland, 70-784

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie-Panstwowy Instytut Badawczy

Warszawa, Poland, 02-781

Russian Federation

RBHI Kursk Regional Clinical Oncology Dispensary

Kislino, Ryshkovsky Rural Council, Kursk Region, Russian Federation, 305 524

Budgetary Healthcare Institution Omsk Region "Clinical Oncological Dispensary"

Omsk, OMSK Region, Russian Federation, 644013

LEC at SBIH "Saint-Petersburg Clinical Research Practical Center of specialized types of

Pesochniy Poselok, Saint-petersburg, Russian Federation, 197758

Private Medical Institution "Euromedservice"

Pushkin, Saint-petersburg, Russian Federation, 196603

RBHI Kursk Regional Clinical Oncology Dispensary

Kursk, Russian Federation, 305 035

FSBI "N.N.Blokhin Medical Research Center of Oncology"

Moscow, Russian Federation, 115478

Singapore

National University Hospital

Singapore, Singapore, 119074

Raffles Hospital

Singapore, Singapore, 188770

Spain

Institut Catala d'Oncologia L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain, 08908

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, Canarias, Spain, 35016

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, Spain, 28222

Complejo Hospitalario De Navarra

Pamplona, Navarra, Spain, 31008

Hospital Teresa Herrera C.H.U.A.C.

A Coruna, Spain, 15006

Hospital De La Santa Creu I Sant Pau

Barcelona, Spain, 08025

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain, 08036

Hospital De La Santa Creu I Sant Pau

Barcelona, Spain, 08041

Institut Catala d'Oncologia Girona

Girona, Spain, 17007

Hospital Universitario Ramon y Cajal

Madrid, Spain, 28034

Hospital Clinico San Carlos

Madrid, Spain, 28040

Hospital Universitario Fundacion Jimenez Diaz

Madrid, Spain, 28040

Hospital Universitario La Fe

Valencia, Spain, 46026

Taiwan

National Taiwan University Hospital

Taipei, Taiwan ROC, Taiwan, 10002

Chang Gung Memorial Hospital - Kaohsiung Branch

Kaohsiung, Taiwan, 83301

Chung Shan Medical University Hospital

Taichung, Taiwan, 402

Taichung Veterans General Hospital

Taichung, Taiwan, 40705

Taipei Veterans General Hospital

Taipei, Taiwan, 112

Turkey

Cukurova University Medical Faculty

Adana, Turkey, 01330

Istanbul University Oncology Institute

Istanbul, Turkey, 34093

Marmara Univ Pendik Training and Research Hospital

Istanbul, Turkey, 34899

Ege University Medical Faculty

Izmir, Turkey, 35100

United Kingdom

The Ipswich Hospital NHS Trust

Ipswich, Suffolk, United Kingdom, IP4 5PD

Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital

Birmingham, WEST Midlands, United Kingdom, B9 5SS

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] October 4, 2019

Statistical Analysis Plan  [PDF] May 26, 2020

More Information

Additional Information:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03052608
• Other Study ID Numbers: B7461006; 2016-003315-35 ( EudraCT Number )
• First Posted: February 14, 2017
• Results First Posted: April 1, 2021
• Last Update Posted: February 20, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

ALK; anaplastic lymphoma kinase; Non-Small-Cell Lung cancer; NSCLC

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Crizotinib; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents