NCT03052608 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2025-11-25

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Progression-Free Survival (PFS) Based on Investigator's Assessment

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outcome · POSTED

Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on BICR Assessment

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outcome · POSTED

Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on Investigator's Assessment

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outcome · POSTED

Intracranial Objective Response Rate (IC-ORR) - Percentage of Participants With Intracranial Objective Response (IC-OR) Based on BICR Assessment

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outcome · POSTED

Intracranial Time to Progression (IC-TTP) Based on BICR Assessment

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outcome · POSTED

Duration of Response (DR) Based on BICR Assessment

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outcome · POSTED

Intracranial Duration of Response (IC-DR) Based on BICR Assessment

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outcome · POSTED

Time to Tumor Response (TTR) Based on BICR Assessment

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outcome · POSTED

Intracranial Time to Tumor Response (IC-TTR) Based on BICR Assessment

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outcome · NOT POSTED

PFS2 Based on Investigator's Assessment

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outcome · POSTED

Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related)

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria

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outcome · POSTED

Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria

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outcome · POSTED

Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Points in Left Ventricular Ejection Fraction (LVEF) Percentage

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outcome · POSTED

Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time

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outcome · POSTED

Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time

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outcome · POSTED

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

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outcome · POSTED

Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment

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outcome · POSTED

Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time

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outcome · POSTED

Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time

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outcome · POSTED

Time to Deterioration (TTD) in Participant Reported Pain in Chest, Dyspnea, or Cough From QLQ-LC13

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outcome · POSTED

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

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Lorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously
intervention Names
Drug: Lorlatinib
label
Lorlatinib
type
EXPERIMENTAL
description
Crizotinib single agent, 250 mg (1 x 250) oral capsules, BID, continuously
intervention Names
Drug: Crizotinib
label
Crizotinib
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Lorlatinib
description
ALK-positive NSCL treatment
name
Lorlatinib
other Names
PF-06463922
type
DRUG
arm Group Labels
Crizotinib
description
ALK-positive NSCL treatment
name
Crizotinib
other Names
Xalkori
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 296
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment
time Frame
From time of Study Start up to 33 months

secondary Outcomes

description
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.
measure
Overall Survival (OS)
time Frame
From time of Study Start up to 33 months
description
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.
measure
Progression-Free Survival (PFS) Based on Investigator's Assessment
time Frame
From time of Study Start up to 33 months
description
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.
measure
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
description
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.
measure
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
description
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.
measure
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
description
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.
measure
Intracranial Time to Progression (IC-TTP) Based on BICR Assessment
time Frame
From time of Study Start up to 33 months
description
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.
measure
Duration of Response (DR) Based on BICR Assessment
time Frame
From time of Study Start up to 33 months
description
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.
measure
Intracranial Duration of Response (IC-DR) Based on BICR Assessment
time Frame
From time of Study Start up to 33 months
description
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.
measure
Time to Tumor Response (TTR) Based on BICR Assessment
time Frame
From time of Study Start up to 33 months
description
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.
measure
Intracranial Time to Tumor Response (IC-TTR) Based on BICR Assessment
time Frame
From time of Study Start up to 33 months
description
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
measure
PFS2 Based on Investigator's Assessment
time Frame
From time of Study Start up to 45 months
description
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.
measure
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

Full 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

Source references

references

citation
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pmid
28501139
type
DERIVED