Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
ALK; anaplastic lymphoma kinase; Non-Small-Cell Lung cancer; NSCLC
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
Interventions
DRUGLorlatinib
ALK-positive NSCL treatment
DRUGCrizotinib
ALK-positive NSCL treatment
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Based on Investigator's Assessment | 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. |
| Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on BICR Assessment | 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. |
| Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on Investigator's Assessment | 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. |
| Intracranial Objective Response Rate (IC-ORR) - Percentage of Participants With Intracranial Objective Response (IC-OR) Based on BICR Assessment | 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. |
| Intracranial Time to Progression (IC-TTP) Based on BICR Assessment | 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. |
| Duration of Response (DR) Based on BICR Assessment | 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. |
| Intracranial Duration of Response (IC-DR) Based on BICR Assessment | 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. |
| Time to Tumor Response (TTR) Based on BICR Assessment | 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. |
| Intracranial Time to Tumor Response (IC-TTR) Based on BICR Assessment | 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. |
| PFS2 Based on Investigator's Assessment | 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 |
| Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | 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. |
| 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 | 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. |
| 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 | 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. |
| Overall Survival (OS) | 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. |
| Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | 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%. |
| Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | 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. |
| Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Points in Left Ventricular Ejection Fraction (LVEF) Percentage | 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. |
| Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | 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. |
| Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | 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. |
| 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 | 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. |
| Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | 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. |
| Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | 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. |
| Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | 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). |
| Time to Deterioration (TTD) in Participant Reported Pain in Chest, Dyspnea, or Cough From QLQ-LC13 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
Countries
Argentina, Australia, Belgium, Canada, China, Czechia, France, Germany, Hong Kong, India, Italy, Japan, Mexico, Netherlands, Poland, Russia, Singapore, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
This phase 3, randomized, open label study was conducted at 104 sites in 23 countries. A total of 296 participants were randomized, 149 to the lorlatinib arm and 147 to the crizotinib arm.
Pre-assignment details
Previously untreated Stage IIIB/IV participants with ALK-positive non-small cell lung cancer were randomized in this study.
Participants by arm
| Arm | Count |
|---|---|
| Lorlatinib Lorlatinib monotherapy at the recommended Phase 2 dose of 100 mg, was administered orally once daily (QD) at approximately the same time of the day on a continuous daily dosing schedule. Each treatment cycle was defined as 28 days. Treatment continued until confirmation of RECIST version 1.1 defined disease progression assessed by the blinded independent central review (unless clinical benefit was still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, death, or the study was terminated by the sponsor, whichever occurred first. | 149 |
| Crizotinib Crizotinib monotherapy at the registered dose of 250 mg, was administered orally twice daily (BID) at approximately the same time in the morning and evening (12 hours apart) on a continuous daily dosing schedule. Each treatment cycle was defined as 28 days. Treatment continued until confirmation of RECIST version 1.1 defined disease progression assessed by the blinded independent central review (unless clinical benefit was still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, death, or the study was terminated by the sponsor, whichever occurred first. | 147 |
| Total | 296 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Long-Term Follow-up Phase | Death | 23 | 28 |
| Long-Term Follow-up Phase | Lost to Follow-up | 0 | 2 |
| Long-Term Follow-up Phase | Ongoing | 122 | 99 |
| Long-Term Follow-up Phase | Withdrawal by Subject | 4 | 18 |
| Treatment Phase | Adverse Event | 10 | 12 |
| Treatment Phase | Death | 6 | 4 |
| Treatment Phase | Global Deterioration of Health Status | 0 | 3 |
| Treatment Phase | Ongoing | 103 | 31 |
| Treatment Phase | Subject decided to continue study treatment as per clinical practice in another hospital. | 0 | 1 |
| Treatment Phase | Subject didn't receive study treatment. | 0 | 1 |
| Treatment Phase | Withdrawal by Subject | 4 | 12 |
Baseline characteristics
| Characteristic | Crizotinib | Total | Lorlatinib |
|---|---|---|---|
| Age, Continuous | 55.6 Years STANDARD_DEVIATION 13.52 | 57.4 Years STANDARD_DEVIATION 13.41 | 59.1 Years STANDARD_DEVIATION 13.12 |
| Race/Ethnicity, Customized Race Asian | 65 Participants | 130 Participants | 65 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Missing | 9 Participants | 21 Participants | 12 Participants |
| Race/Ethnicity, Customized Race White | 72 Participants | 144 Participants | 72 Participants |
| Sex: Female, Male Female | 91 Participants | 175 Participants | 84 Participants |
| Sex: Female, Male Male | 56 Participants | 121 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 23 / 149 | 28 / 142 |
| other Total, other adverse events | 148 / 149 | 140 / 142 |
| serious Total, serious adverse events | 51 / 149 | 39 / 142 |
Outcome results
Primary
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.
Time frame: From time of Study Start up to 33 months
Population: The full analysis (FA) population included all participants who were randomized, and participants were classified according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment | NA Months |
| Crizotinib | Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment | 9.3 Months |
Comparison: The study was designed to test the null hypothesis H0: λ ≥1 versus the alternative hypothesis HA: λ \<1, where λ is the hazard ratio (HR; Lorlatinib/Crizotinib). Evaluation of 177 PFS events was required to have at least 90% power to detect a HR of 0.611 using a one-sided stratified log-rank test at a significance level of 0.025 (one-sided), and a 2-look group-sequential design with a Lan-DeMets (O'Brien-Fleming) α-spending function to determine the efficacy boundaries.p-value: <0.000195% CI: [0.191, 0.413]one-sided stratified log-rank
Secondary
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.
Time frame: From Baseline up to Cycle 38 Day 1
Population: Participants from the FA population who completed a baseline (last patient-reported outcome (PRO) assessment prior to the first dose of study treatment) and at least 1 post-baseline PRO assessment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lorlatinib | 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 | Pain | -4.60 Units on a scale |
| Lorlatinib | 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 | Physical Functioning | 4.84 Units on a scale |
| Lorlatinib | 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 | Role Functioning | 6.86 Units on a scale |
| Lorlatinib | 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 | Emotional Functioning | 8.77 Units on a scale |
| Lorlatinib | 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 | Cognitive Functioning | -4.20 Units on a scale |
| Lorlatinib | 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 | Dyspnoea | -7.02 Units on a scale |
| Lorlatinib | 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 | Insomnia | -17.34 Units on a scale |
| Lorlatinib | 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 | Appetite Loss | -13.15 Units on a scale |
| Lorlatinib | 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 | Constipation | -2.40 Units on a scale |
| Lorlatinib | 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 | Diarrhea | -0.92 Units on a scale |
| Lorlatinib | 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 | Financial Difficulties | -6.79 Units on a scale |
| Lorlatinib | 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 | Social Functioning | 7.00 Units on a scale |
| Lorlatinib | 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 | Fatigue | -9.93 Units on a scale |
| Lorlatinib | 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 | Nausea and Vomiting | -4.35 Units on a scale |
| Lorlatinib | 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 | Global QOL | 8.60 Units on a scale |
| Crizotinib | 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 | Financial Difficulties | -5.74 Units on a scale |
| Crizotinib | 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 | Global QOL | 3.95 Units on a scale |
| Crizotinib | 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 | Appetite Loss | -3.95 Units on a scale |
| Crizotinib | 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 | Physical Functioning | 2.82 Units on a scale |
| Crizotinib | 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 | Role Functioning | 4.78 Units on a scale |
| Crizotinib | 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 | Constipation | 2.53 Units on a scale |
| Crizotinib | 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 | Emotional Functioning | 6.20 Units on a scale |
| Crizotinib | 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 | Fatigue | -4.26 Units on a scale |
| Crizotinib | 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 | Cognitive Functioning | -1.02 Units on a scale |
| Crizotinib | 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 | Social Functioning | 4.72 Units on a scale |
| Crizotinib | 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 | Pain | -5.76 Units on a scale |
| Crizotinib | 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 | Diarrhea | 11.12 Units on a scale |
| Crizotinib | 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 | Dyspnoea | -8.75 Units on a scale |
| Crizotinib | 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 | Nausea and Vomiting | 3.51 Units on a scale |
| Crizotinib | 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 | Insomnia | -9.39 Units on a scale |
Comparison: This is the analysis for QLQ-C30 Global QOL. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.009695% CI: [1.14, 8.16]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Physical Functioning. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.189795% CI: [-1.01, 5.05]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Role Functioning. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.299995% CI: [-1.87, 6.04]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Emotional Functioning. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.055395% CI: [-0.06, 5.22]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Cognitive Functioning. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.058895% CI: [-6.47, 0.12]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Social Functioning. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.211895% CI: [-1.3, 5.85]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Fatigue. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.003295% CI: [-9.42, -1.92]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Nausea and Vomiting. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: <0.000195% CI: [-9.86, -5.86]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Pain. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.53195% CI: [-2.49, 4.82]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Dyspnoea. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.360295% CI: [-1.98, 5.43]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Insomnia. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: <0.000195% CI: [-11.25, -4.64]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Appetite Loss. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: <0.000195% CI: [-11.8, -6.62]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Constipation. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.019895% CI: [-9.07, -0.79]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Diarrhea. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: <0.000195% CI: [-15.49, -8.58]Mixed Models Analysis
Comparison: This is the analysis for QLQ-C30 Financial Difficulties. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.594795% CI: [-4.9, 2.82]Mixed Models Analysis
Secondary
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).
Time frame: Baseline, Day 1 of all cycles from Cycle 2 to Cycle 38, and End of Treatment
Population: Number of Participants Analyzed included all participants in the PRO analysis population within each treatment group. Number Analyzed included all participants with at least a baseline and postbaseline assessment at the visit.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 22 Day 1 | 0.079 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 4 Day 1 | 0.089 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 6 Day 1 | 0.077 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 7 Day 1 | 0.062 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 8 Day 1 | 0.074 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 10 Day 1 | 0.074 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 14 Day 1 | 0.091 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 16 Day 1 | 0.091 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 18 Day 1 | 0.103 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 20 Day 1 | 0.103 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 26 Day 1 | 0.065 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 27 Day 1 | 0.042 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 29 Day 1 | 0.046 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 30 Day 1 | 0.099 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 33 Day 1 | 0.058 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 34 Day 1 | 0.062 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 35 Day 1 | 0.129 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 37 Day 1 | 0.056 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 38 Day 1 | 0.232 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 5 Day 1 | 0.047 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 9 Day 1 | 0.060 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 11 Day 1 | 0.083 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 12 Day 1 | 0.080 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 13 Day 1 | 0.081 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 15 Day 1 | 0.077 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 17 Day 1 | 0.098 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 19 Day 1 | 0.100 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 21 Day 1 | 0.068 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 2 Day 1 | 0.078 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 23 Day 1 | 0.060 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 24 Day 1 | 0.082 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 25 Day 1 | 0.047 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 28 Day 1 | 0.024 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 31 Day 1 | 0.086 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 32 Day 1 | 0.058 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 36 Day 1 | -0.027 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | End of Treatment | -0.033 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 3 Day 1 | 0.071 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 2 Day 1 | 0.064 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 22 Day 1 | 0.052 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 3 Day 1 | 0.101 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 5 Day 1 | 0.100 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 6 Day 1 | 0.070 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 8 Day 1 | 0.061 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 7 Day 1 | 0.046 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | End of Treatment | 0.001 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 9 Day 1 | 0.050 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 10 Day 1 | 0.050 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 11 Day 1 | 0.057 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 23 Day 1 | 0.006 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 14 Day 1 | 0.021 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 31 Day 1 | -0.024 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 16 Day 1 | 0.051 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 17 Day 1 | -0.016 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 12 Day 1 | 0.049 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 18 Day 1 | 0.021 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 19 Day 1 | 0.027 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 24 Day 1 | -0.053 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 25 Day 1 | 0.045 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 13 Day 1 | 0.055 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 36 Day 1 | 0.042 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 28 Day 1 | -0.040 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 15 Day 1 | 0.036 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 26 Day 1 | 0.039 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 30 Day 1 | -0.028 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 32 Day 1 | -0.139 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 27 Day 1 | 0.021 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 20 Day 1 | 0.025 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 34 Day 1 | 0.042 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 33 Day 1 | -0.024 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 35 Day 1 | 0.042 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 21 Day 1 | 0.040 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 29 Day 1 | 0.041 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time | Cycle 4 Day 1 | 0.098 Units on a scale |
Secondary
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.
Time frame: Baseline, Day 1 of all cycles from Cycle 2 to Cycle 38, and End of Treatment
Population: Number of Participants Analyzed included all participants in the EQ-5D-5L PRO analysis population within each treatment group. Number Analyzed included all participants with at least a baseline and postbaseline assessment at the visit.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 2 Day 1 | 6.0 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 3 Day 1 | 6.0 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 4 Day 1 | 7.1 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 6 Day 1 | 6.5 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 8 Day 1 | 6.7 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 9 Day 1 | 6.4 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 10 Day 1 | 7.2 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 11 Day 1 | 8.1 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 12 Day 1 | 7.6 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 13 Day 1 | 7.5 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 14 Day 1 | 6.7 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 15 Day 1 | 6.1 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 16 Day 1 | 6.9 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 17 Day 1 | 8.3 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 18 Day 1 | 8.7 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 20 Day 1 | 7.9 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 22 Day 1 | 4.5 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 23 Day 1 | 5.2 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 24 Day 1 | 4.9 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 25 Day 1 | 4.0 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 27 Day 1 | 4.6 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 28 Day 1 | 6.0 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 29Day 1 | 7.4 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 30 Day 1 | 9.1 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 31 Day 1 | 7.8 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 32 Day 1 | 7.9 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 33 Day 1 | 4.4 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 34 Day 1 | -0.5 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 35 Day 1 | 0.0 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 36 Day 1 | -4.5 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 37 Day 1 | -17.5 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 5 Day 1 | 4.3 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 7 Day 1 | 5.5 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 19 Day 1 | 6.8 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 21 Day 1 | 7.2 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 26 Day 1 | 7.9 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 38 Day 1 | 25.0 Units on a scale |
| Lorlatinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | End of Treatment | -3.7 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 3 Day 1 | 5.3 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 33 Day 1 | -2.5 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 4 Day 1 | 5.6 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 5 Day 1 | 5.1 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 25 Day 1 | 1.4 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 6 Day 1 | 4.5 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 35 Day 1 | 20.0 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 8 Day 1 | 4.2 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 27 Day 1 | 3.0 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 9 Day 1 | 3.9 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 20 Day 1 | 3.4 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 10 Day 1 | 3.9 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 28 Day 1 | 2.7 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 11 Day 1 | 2.0 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 36 Day 1 | 15.0 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 12 Day 1 | 4.8 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 29Day 1 | 8.2 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 2 Day 1 | 3.1 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 14 Day 1 | 2.3 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 30 Day 1 | 2.8 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 15 Day 1 | 1.5 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | End of Treatment | -1.3 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 16 Day 1 | 2.4 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 31 Day 1 | 0.0 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 17 Day 1 | 1.1 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 26 Day 1 | 2.0 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 18 Day 1 | 1.3 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 19 Day 1 | 2.8 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 32 Day 1 | 2.5 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 21 Day 1 | 3.3 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 7 Day 1 | 4.0 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 22 Day 1 | 1.9 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 13 Day 1 | 5.8 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 23 Day 1 | -0.6 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 34 Day 1 | 20.0 Units on a scale |
| Crizotinib | Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time | Cycle 24 Day 1 | -3.0 Units on a scale |
Secondary
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.
Time frame: From Baseline up to Cycle 38 Day 1
Population: Participants from the FA population who completed a baseline (last patient-reported outcome (PRO) assessment prior to the first dose of study treatment) and at least 1 post-baseline PRO assessment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lorlatinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Dyspnoea | -4.36 Units on a scale |
| Lorlatinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Coughing | -21.21 Units on a scale |
| Lorlatinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Haemoptysis | -2.53 Units on a scale |
| Lorlatinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Sore Mouth | 0.56 Units on a scale |
| Lorlatinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Dysphagia | -1.35 Units on a scale |
| Lorlatinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Alopecia | 1.61 Units on a scale |
| Lorlatinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Pain in Chest | -9.54 Units on a scale |
| Lorlatinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Pain in Arm or Shoulder | -6.93 Units on a scale |
| Lorlatinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Pain in Other Parts | -2.31 Units on a scale |
| Lorlatinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Peripheral Neuropathy | 11.56 Units on a scale |
| Crizotinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Peripheral Neuropathy | 6.20 Units on a scale |
| Crizotinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Dyspnoea | -4.90 Units on a scale |
| Crizotinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Pain in Other Parts | -5.67 Units on a scale |
| Crizotinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Coughing | -16.66 Units on a scale |
| Crizotinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Alopecia | 1.81 Units on a scale |
| Crizotinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Haemoptysis | -2.65 Units on a scale |
| Crizotinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Pain in Arm or Shoulder | -7.38 Units on a scale |
| Crizotinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Sore Mouth | -0.60 Units on a scale |
| Crizotinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Pain in Chest | -9.01 Units on a scale |
| Crizotinib | Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment | Dysphagia | 0.16 Units on a scale |
Comparison: This is the analysis for QLQ-LC13 Dyspnoea. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.725495% CI: [-2.51, 3.6]Mixed Models Analysis
Comparison: This is the analysis for QLQ-LC13 Coughing. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.011595% CI: [-8.06, -1.03]Mixed Models Analysis
Comparison: This is the analysis for QLQ-LC13 Haemoptysis. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.782495% CI: [-0.75, 0.99]Mixed Models Analysis
Comparison: This is the analysis for QLQ-LC13 Sore Mouth. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.298895% CI: [-1.04, 3.36]Mixed Models Analysis
Comparison: This is the analysis for QLQ-LC13 Dysphagia. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.191695% CI: [-3.79, 0.76]Mixed Models Analysis
Comparison: This is the analysis for QLQ-LC13 Peripheral Neuropathy. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.027995% CI: [0.59, 10.15]Mixed Models Analysis
Comparison: This is the analysis for QLQ-LC13 Alopecia. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.916295% CI: [-3.89, 3.49]Mixed Models Analysis
Comparison: This is the analysis for QLQ-LC13 Pain in Chest. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.669895% CI: [-2.96, 1.9]Mixed Models Analysis
Comparison: This is the analysis for QLQ-LC13 Pain in Arm or Shoulder. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.803595% CI: [-3.13, 4.04]Mixed Models Analysis
Comparison: This is the analysis for QLQ-LC13 Pain in Other Parts. Estimated change from baseline was based on random intercept random slope mixed-effects model with an intercept term, treatment, time (as a continuous variable), treatment-by-time, baseline and randomization stratification factors as covariates.p-value: 0.114395% CI: [-0.82, 7.55]Mixed Models Analysis
Secondary
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.
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
Population: Number of Participants Analyzed included all participants in the safety analysis population within each treatment group. Number Analyzed included all participants with at least a baseline and postbaseline assessment at the visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 26 Day 1 | -3.2 Units on a scale | Standard Deviation 6.87 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 6 Day 1 | -2.6 Units on a scale | Standard Deviation 6.61 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 14 Day 1 | -3.3 Units on a scale | Standard Deviation 6.82 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 16 Day 1 | -3.3 Units on a scale | Standard Deviation 6.87 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 22 Day 1 | -3.2 Units on a scale | Standard Deviation 6.95 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 24 Day 1 | -3.1 Units on a scale | Standard Deviation 5.97 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 3 Day 1 | -2.5 Units on a scale | Standard Deviation 5.85 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 28 Day 1 | -3.0 Units on a scale | Standard Deviation 6.53 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 30 Day 1 | -4.8 Units on a scale | Standard Deviation 8 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 34 Day 1 | -2.3 Units on a scale | Standard Deviation 12.42 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | End of Treatment | 0.8 Units on a scale | Standard Deviation 4.49 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 2 Day 1 | -1.8 Units on a scale | Standard Deviation 5.52 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 4 Day 1 | -2.9 Units on a scale | Standard Deviation 5.73 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 5 Day 1 | -2.5 Units on a scale | Standard Deviation 6.28 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 8 Day 1 | -3.2 Units on a scale | Standard Deviation 6.18 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 10 Day 1 | -3.0 Units on a scale | Standard Deviation 6.3 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 12 Day 1 | -3.6 Units on a scale | Standard Deviation 6.05 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 18 Day 1 | -3.7 Units on a scale | Standard Deviation 7.26 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 20 Day 1 | -3.3 Units on a scale | Standard Deviation 6.24 |
| Lorlatinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 32 Day 1 | -5.0 Units on a scale | Standard Deviation 14.14 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 2 Day 1 | -1.2 Units on a scale | Standard Deviation 5.62 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 3 Day 1 | -2.7 Units on a scale | Standard Deviation 5.78 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 5 Day 1 | -3.0 Units on a scale | Standard Deviation 6.24 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 30 Day 1 | 1.3 Units on a scale | Standard Deviation 3.2 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 4 Day 1 | -3.6 Units on a scale | Standard Deviation 6.6 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 14 Day 1 | -2.5 Units on a scale | Standard Deviation 5.57 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 18 Day 1 | -2.6 Units on a scale | Standard Deviation 4.3 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 20 Day 1 | -2.4 Units on a scale | Standard Deviation 4.62 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 6 Day 1 | -2.9 Units on a scale | Standard Deviation 6.65 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 32 Day 1 | 7.5 Units on a scale | Standard Deviation 9.19 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 24 Day 1 | 2.3 Units on a scale | Standard Deviation 9.31 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 8 Day 1 | -1.9 Units on a scale | Standard Deviation 6.56 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 26 Day 1 | -0.8 Units on a scale | Standard Deviation 3.81 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 36 Day 1 | 0.0 Units on a scale | — |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 28 Day 1 | 0.2 Units on a scale | Standard Deviation 7.65 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 10 Day 1 | -2.6 Units on a scale | Standard Deviation 5.98 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 22 Day 1 | -2.5 Units on a scale | Standard Deviation 4.82 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 34 Day 1 | 0.0 Units on a scale | — |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 12 Day 1 | -2.1 Units on a scale | Standard Deviation 6.23 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | End of Treatment | -0.2 Units on a scale | Standard Deviation 7.45 |
| Crizotinib | Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time | Cycle 16 Day 1 | -2.3 Units on a scale | Standard Deviation 5.77 |
Secondary
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.
Time frame: From time of Study Start up to 33 months
Population: Participants with a confirmed objective response (complete response or partial response) per RECIST version 1.1 in the FA population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Duration of Response (DR) Based on BICR Assessment | NA Months |
| Crizotinib | Duration of Response (DR) Based on BICR Assessment | 11.0 Months |
Secondary
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.
Time frame: From time of Study Start up to 33 months
Population: Participants with brain metastases at baseline and confirmed intracranial complete response or partial response in the FA population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Intracranial Duration of Response (IC-DR) Based on BICR Assessment | NA Months |
| Crizotinib | Intracranial Duration of Response (IC-DR) Based on BICR Assessment | 9.4 Months |
Secondary
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.
Time frame: From time of Study Start up to 33 months
Population: The subset of the FA population with at least 1 baseline intracranial lesion (based on BICR intracranial assessment).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lorlatinib | Intracranial Objective Response Rate (IC-ORR) - Percentage of Participants With Intracranial Objective Response (IC-OR) Based on BICR Assessment | 65.8 Percentage of participants |
| Crizotinib | Intracranial Objective Response Rate (IC-ORR) - Percentage of Participants With Intracranial Objective Response (IC-OR) Based on BICR Assessment | 20.0 Percentage of participants |
p-value: <0.000195% CI: [2.586, 27.233]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: From time of Study Start up to 33 months
Population: The FA population included all participants who were randomized, and participants were classified according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Intracranial Time to Progression (IC-TTP) Based on BICR Assessment | NA Months |
| Crizotinib | Intracranial Time to Progression (IC-TTP) Based on BICR Assessment | 16.6 Months |
p-value: <0.000195% CI: [0.026, 0.17]one-sided stratified log-rank
Secondary
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.
Time frame: From time of Study Start up to 33 months
Population: Participants with brain metastases at baseline and confirmed intracranial complete response or partial response in the FA population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Intracranial Time to Tumor Response (IC-TTR) Based on BICR Assessment | 1.9 Months |
| Crizotinib | Intracranial Time to Tumor Response (IC-TTR) Based on BICR Assessment | 1.8 Months |
Secondary
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.
Time frame: From Baseline up to 33 months
Population: Participants in the safety analysis population who had at least one on-study assessment for the parameter of interest.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | 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 | Hypocalcemia (Postbaseline Maximum Grade 3) | 1 Participants |
| Lorlatinib | 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 | Alkaline phosphate increased (Postbaseline Maximum Grade 3) | 0 Participants |
| Lorlatinib | 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 | Creatine kinase increased (Postbaseline Maximum Grade 3) | 3 Participants |
| Lorlatinib | 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 | Creatinine increased (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Gamma glutamyl transferase increased (Postbaseline Maximum Grade 3) | 9 Participants |
| Lorlatinib | 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 | Hypercalcemia (Postbaseline Maximum Grade 3) | 0 Participants |
| Lorlatinib | 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 | Hypernatremia (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Hypokalemia (Postbaseline Maximum Grade 3) | 0 Participants |
| Lorlatinib | 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 | Hypokalemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Hypophosphatemia (Postbaseline Maximum Grade 3) | 3 Participants |
| Lorlatinib | 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 | Hypophosphatemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Lipase increased (Postbaseline Maximum Grade 3) | 8 Participants |
| Lorlatinib | 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 | Alanine aminotransferase increased (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Alkaline phosphate increased (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Aspartate aminotransferase increased (Postbaseline Maximum Grade 3) | 3 Participants |
| Lorlatinib | 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 | Aspartate aminotransferase increased (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Blood bilirubin increased (Postbaseline Maximum Grade 3) | 0 Participants |
| Lorlatinib | 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 | Blood bilirubin increased (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Creatine kinase increased (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Creatinine increased (Postbaseline Maximum Grade 3) | 1 Participants |
| Lorlatinib | 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 | Gamma glutamyl transferase increased (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Hypercalcemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Hyperglycemia (Postbaseline Maximum Grade 3) | 9 Participants |
| Lorlatinib | 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 | Hyperglycemia (Postbaseline Maximum Grade 4) | 1 Participants |
| Lorlatinib | 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 | Hyperkalemia (Postbaseline Maximum Grade 3) | 2 Participants |
| Lorlatinib | 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 | Hyperkalemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Hypermagnesemia (Postbaseline Maximum Grade 3) | 2 Participants |
| Lorlatinib | 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 | Hypermagnesemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Hypernatremia (Postbaseline Maximum Grade 3) | 0 Participants |
| Lorlatinib | 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 | Hypoalbuminemia (Postbaseline Maximum Grade 3) | 1 Participants |
| Lorlatinib | 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 | Hypoalbuminemia (Postbaseline Maximum Grade 4) | NA Participants |
| Lorlatinib | 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 | Alanine aminotransferase increased (Postbaseline Maximum Grade 3) | 4 Participants |
| Lorlatinib | 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 | Hypocalcemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Hypoglycemia (Postbaseline Maximum Grade 3) | 0 Participants |
| Lorlatinib | 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 | Hypoglycemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Hypomagnesemia (Postbaseline Maximum Grade 3) | 0 Participants |
| Lorlatinib | 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 | Hypomagnesemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Hyponatremia (Postbaseline Maximum Grade 3) | 5 Participants |
| Lorlatinib | 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 | Hyponatremia (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Lipase increased (Postbaseline Maximum Grade 4) | 3 Participants |
| Lorlatinib | 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 | Serum amylase increased (Postbaseline Maximum Grade 3) | 1 Participants |
| Lorlatinib | 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 | Serum amylase increased (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Hypoalbuminemia (Postbaseline Maximum Grade 4) | NA Participants |
| Crizotinib | 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 | Hypercalcemia (Postbaseline Maximum Grade 3) | 0 Participants |
| Crizotinib | 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 | Alkaline phosphate increased (Postbaseline Maximum Grade 3) | 1 Participants |
| Crizotinib | 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 | Hypomagnesemia (Postbaseline Maximum Grade 3) | 0 Participants |
| Crizotinib | 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 | Creatine kinase increased (Postbaseline Maximum Grade 3) | 5 Participants |
| Crizotinib | 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 | Creatinine increased (Postbaseline Maximum Grade 3) | 3 Participants |
| Crizotinib | 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 | Hypocalcemia (Postbaseline Maximum Grade 3) | 0 Participants |
| Crizotinib | 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 | Creatinine increased (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Hyperglycemia (Postbaseline Maximum Grade 3) | 3 Participants |
| Crizotinib | 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 | Gamma glutamyl transferase increased (Postbaseline Maximum Grade 4) | 1 Participants |
| Crizotinib | 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 | Hypophosphatemia (Postbaseline Maximum Grade 3) | 4 Participants |
| Crizotinib | 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 | Hypercalcemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Hyperglycemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Hypocalcemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Hyperkalemia (Postbaseline Maximum Grade 3) | 3 Participants |
| Crizotinib | 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 | Hypokalemia (Postbaseline Maximum Grade 3) | 3 Participants |
| Crizotinib | 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 | Serum amylase increased (Postbaseline Maximum Grade 3) | 2 Participants |
| Crizotinib | 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 | Hypomagnesemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Hyponatremia (Postbaseline Maximum Grade 4) | 1 Participants |
| Crizotinib | 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 | Hyperkalemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Hypoglycemia (Postbaseline Maximum Grade 3) | 0 Participants |
| Crizotinib | 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 | Hypophosphatemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Hypermagnesemia (Postbaseline Maximum Grade 3) | 1 Participants |
| Crizotinib | 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 | Lipase increased (Postbaseline Maximum Grade 3) | 6 Participants |
| Crizotinib | 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 | Serum amylase increased (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Alanine aminotransferase increased (Postbaseline Maximum Grade 3) | 5 Participants |
| Crizotinib | 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 | Hyponatremia (Postbaseline Maximum Grade 3) | 10 Participants |
| Crizotinib | 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 | Alanine aminotransferase increased (Postbaseline Maximum Grade 4) | 1 Participants |
| Crizotinib | 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 | Hypermagnesemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Alkaline phosphate increased (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Hypoglycemia (Postbaseline Maximum Grade 4) | 1 Participants |
| Crizotinib | 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 | Aspartate aminotransferase increased (Postbaseline Maximum Grade 3) | 4 Participants |
| Crizotinib | 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 | Hypernatremia (Postbaseline Maximum Grade 3) | 0 Participants |
| Crizotinib | 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 | Aspartate aminotransferase increased (Postbaseline Maximum Grade 4) | 1 Participants |
| Crizotinib | 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 | Hypernatremia (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Blood bilirubin increased (Postbaseline Maximum Grade 3) | 0 Participants |
| Crizotinib | 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 | Hypokalemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Blood bilirubin increased (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Hypoalbuminemia (Postbaseline Maximum Grade 3) | 9 Participants |
| Crizotinib | 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 | Creatine kinase increased (Postbaseline Maximum Grade 4) | 2 Participants |
| Crizotinib | 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 | Lipase increased (Postbaseline Maximum Grade 4) | 1 Participants |
| Crizotinib | 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 | Gamma glutamyl transferase increased (Postbaseline Maximum Grade 3) | 8 Participants |
Secondary
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.
Time frame: From Baseline up to 33 months
Population: Participants in the safety analysis population who had at least one on-study assessment for the parameter of interest.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | 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 | Hemoglobin increased (Postbaseline Maximum Grade 3) | 0 Participants |
| Lorlatinib | 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 | Lymphocyte count increased (Postbaseline Maximum Grade 3) | 0 Participants |
| Lorlatinib | 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 | White blood cell decreased (Postbaseline Maximum Grade 4) | 0 Participants |
| Lorlatinib | 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 | Lymphocyte count increased (Postbaseline Maximum Grade 4) | NA Participants |
| Lorlatinib | 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 | Hemoglobin increased (Postbaseline Maximum Grade 4) | NA Participants |
| Lorlatinib | 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 | Neutrophil count decreased (Postbaseline Maximum Grade 3) | 1 Participants |
| Lorlatinib | 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 | Anemia (Postbaseline Maximum Grade 4) | NA Participants |
| Lorlatinib | 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 | Neutrophil count decreased (Postbaseline Maximum Grade 4) | 1 Participants |
| Lorlatinib | 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 | Lymphocyte count decreased (Postbaseline Maximum Grade 3) | 2 Participants |
| Lorlatinib | 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 | Platelet count decreased (Postbaseline Maximum Grade 3) | 0 Participants |
| Lorlatinib | 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 | Anemia (Postbaseline Maximum Grade 3) | 3 Participants |
| Lorlatinib | 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 | Lymphocyte count decreased (Postbaseline Maximum Grade 4) | 2 Participants |
| Lorlatinib | 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 | White blood cell decreased (Postbaseline Maximum Grade 3) | 0 Participants |
| Lorlatinib | 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 | Platelet count decreased (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | White blood cell decreased (Postbaseline Maximum Grade 3) | 5 Participants |
| Crizotinib | 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 | White blood cell decreased (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Anemia (Postbaseline Maximum Grade 3) | 4 Participants |
| Crizotinib | 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 | Anemia (Postbaseline Maximum Grade 4) | NA Participants |
| Crizotinib | 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 | Hemoglobin increased (Postbaseline Maximum Grade 3) | 0 Participants |
| Crizotinib | 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 | Hemoglobin increased (Postbaseline Maximum Grade 4) | NA Participants |
| Crizotinib | 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 | Lymphocyte count decreased (Postbaseline Maximum Grade 3) | 7 Participants |
| Crizotinib | 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 | Lymphocyte count decreased (Postbaseline Maximum Grade 4) | 1 Participants |
| Crizotinib | 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 | Lymphocyte count increased (Postbaseline Maximum Grade 3) | 0 Participants |
| Crizotinib | 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 | Lymphocyte count increased (Postbaseline Maximum Grade 4) | NA Participants |
| Crizotinib | 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 | Neutrophil count decreased (Postbaseline Maximum Grade 3) | 19 Participants |
| Crizotinib | 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 | Neutrophil count decreased (Postbaseline Maximum Grade 4) | 4 Participants |
| Crizotinib | 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 | Platelet count decreased (Postbaseline Maximum Grade 3) | 1 Participants |
| Crizotinib | 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 | Platelet count decreased (Postbaseline Maximum Grade 4) | 0 Participants |
Secondary
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.
Time frame: From Baseline up to 33 months
Population: Participants in the safety analysis population who had at least one on-study assessment for the parameter of interest.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | 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 | Cholesterol high (Postbaseline Maximum Grade 3) | 26 Participants |
| Lorlatinib | 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 | Hypertriglyceridemia (Postbaseline Maximum Grade 3) | 20 Participants |
| Lorlatinib | 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 | Hypertriglyceridemia (Postbaseline Maximum Grade 4) | 13 Participants |
| Lorlatinib | 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 | Cholesterol high (Postbaseline Maximum Grade 4) | 3 Participants |
| Crizotinib | 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 | Hypertriglyceridemia (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Cholesterol high (Postbaseline Maximum Grade 3) | 0 Participants |
| Crizotinib | 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 | Cholesterol high (Postbaseline Maximum Grade 4) | 0 Participants |
| Crizotinib | 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 | Hypertriglyceridemia (Postbaseline Maximum Grade 3) | 0 Participants |
Secondary
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.
Time frame: From Baseline up to 33 months
Population: All participants in the safety analysis population who had at least one on-study assessment for the parameter of interest.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lorlatinib | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Points in Left Ventricular Ejection Fraction (LVEF) Percentage | 2 Participants |
| Crizotinib | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Points in Left Ventricular Ejection Fraction (LVEF) Percentage | 1 Participants |
Secondary
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.
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
Population: Number of Participants Analyzed included all participants in the safety analysis population within each treatment group. Number Analyzed included all participants with assessment scores at each specified time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Baseline | 3 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 2 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 3 Day 1 | 1 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 4 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 5 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 6 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 8 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 10 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 12 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 28 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 30 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 32 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 34 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 36 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 38 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | End of Treatment | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 14 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 16 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 18 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 20 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 22 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 24 Day 1 | 0 Participants |
| Lorlatinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 26 Day 1 | 1 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Baseline | 7 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 14 Day 1 | 0 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 2 Day 1 | 5 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 32 Day 1 | 0 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 3 Day 1 | 1 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 20 Day 1 | 0 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 4 Day 1 | 1 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 34 Day 1 | 0 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 5 Day 1 | 1 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 16 Day 1 | 0 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 6 Day 1 | 2 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 36 Day 1 | 0 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 8 Day 1 | 2 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 24 Day 1 | 1 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 10 Day 1 | 1 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 18 Day 1 | 0 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 12 Day 1 | 0 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 26 Day 1 | 0 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | End of Treatment | 0 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 28 Day 1 | 0 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 22 Day 1 | 0 Participants |
| Crizotinib | Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time | Cycle 30 Day 1 | 0 Participants |
Secondary
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.
Time frame: From time of Study Start up to 33 months
Population: The safety analysis population included all participants who received at least 1 dose of study drug. Participants were classified according to the treatment assigned at randomization unless the incorrect treatment(s) were received throughout the dosing period, in which case participants were classified according to the first study treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | SAEs (all-causality) | 51 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | Maximum Grade 3 or 4 AEs (all-causality) | 108 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs causing study treatment discontinuation (all-causality) | 10 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | SAEs (treatment-related) | 12 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | Maximum Grade 3 or 4 AEs (treatment-related) | 83 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | Maximum Grade 5 AEs (all-causality) | 7 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | Maximum Grade 5 AEs (treatment-related) | 2 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs causing study discontinuation (all-causality) | 7 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs causing study discontinuation (treatment-related) | 2 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs causing study treatment discontinuation (treatment-related) | 7 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs causing dose reduction or temporary discontinuation (all-causality) | 79 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs causing dose reduction or temporary discontinuation (treatment-related) | 60 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs (all-causality) | 149 Participants |
| Lorlatinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs (treatment-related) | 144 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs causing dose reduction or temporary discontinuation (all-causality) | 71 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs causing study discontinuation (all-causality) | 8 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs (all-causality) | 140 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs causing study treatment discontinuation (all-causality) | 13 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | Maximum Grade 5 AEs (all-causality) | 7 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | SAEs (all-causality) | 39 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs causing study discontinuation (treatment-related) | 0 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | SAEs (treatment-related) | 7 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | Maximum Grade 3 or 4 AEs (all-causality) | 79 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs causing dose reduction or temporary discontinuation (treatment-related) | 54 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | Maximum Grade 3 or 4 AEs (treatment-related) | 52 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs causing study treatment discontinuation (treatment-related) | 7 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | AEs (treatment-related) | 133 Participants |
| Crizotinib | Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) | Maximum Grade 5 AEs (treatment-related) | 0 Participants |
Secondary
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.
Time frame: at Screening, Cycle 2 Day 1 and Cycle 7 Day 1
Population: Number of Participants Analyzed included all participants in the plasma CNA analysis population within each treatment group at screening. Number Analyzed included all participants in the plasma CNA analysis population within each treatment group at the specified visit.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Lorlatinib | 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 | Cycle 2 Day 1 | No Circulating Free Deoxyribonucleic Acid (cfDNA) Detected | 53 Participants |
| Lorlatinib | 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 | Cycle 2 Day 1 | Other (Sample failed analysis, uninformative, or not analyzed.) | 4 Participants |
| Lorlatinib | 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 | at Screening | ≥1 ALK Mutation Detected | 5 Participants |
| Lorlatinib | 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 | at Screening | No ALK Mutation Detected | 88 Participants |
| Lorlatinib | 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 | at Screening | No Circulating Free Deoxyribonucleic Acid (cfDNA) Detected | 32 Participants |
| Lorlatinib | 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 | at Screening | Other (Sample failed analysis, uninformative, or not analyzed.) | 5 Participants |
| Lorlatinib | 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 | Cycle 2 Day 1 | ≥1 ALK Mutation Detected | 2 Participants |
| Lorlatinib | 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 | Cycle 2 Day 1 | No ALK Mutation Detected | 66 Participants |
| Lorlatinib | 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 | Cycle 7 Day 1 | ≥1 ALK Mutation Detected | 3 Participants |
| Lorlatinib | 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 | Cycle 7 Day 1 | No ALK Mutation Detected | 45 Participants |
| Lorlatinib | 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 | Cycle 7 Day 1 | No Circulating Free Deoxyribonucleic Acid (cfDNA) Detected | 52 Participants |
| Lorlatinib | 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 | Cycle 7 Day 1 | Other (Sample failed analysis, uninformative, or not analyzed.) | 3 Participants |
| Crizotinib | 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 | Cycle 7 Day 1 | No Circulating Free Deoxyribonucleic Acid (cfDNA) Detected | 35 Participants |
| Crizotinib | 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 | Cycle 2 Day 1 | No Circulating Free Deoxyribonucleic Acid (cfDNA) Detected | 58 Participants |
| Crizotinib | 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 | Cycle 2 Day 1 | ≥1 ALK Mutation Detected | 3 Participants |
| Crizotinib | 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 | Cycle 2 Day 1 | Other (Sample failed analysis, uninformative, or not analyzed.) | 2 Participants |
| Crizotinib | 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 | Cycle 7 Day 1 | No ALK Mutation Detected | 42 Participants |
| Crizotinib | 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 | at Screening | ≥1 ALK Mutation Detected | 6 Participants |
| Crizotinib | 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 | Cycle 2 Day 1 | No ALK Mutation Detected | 55 Participants |
| Crizotinib | 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 | at Screening | No ALK Mutation Detected | 91 Participants |
| Crizotinib | 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 | Cycle 7 Day 1 | Other (Sample failed analysis, uninformative, or not analyzed.) | 2 Participants |
| Crizotinib | 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 | at Screening | No Circulating Free Deoxyribonucleic Acid (cfDNA) Detected | 25 Participants |
| Crizotinib | 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 | Cycle 7 Day 1 | ≥1 ALK Mutation Detected | 5 Participants |
| Crizotinib | 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 | at Screening | Other (Sample failed analysis, uninformative, or not analyzed.) | 3 Participants |
Secondary
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.
Time frame: at Screening, Cycle 2 Day 1 and Cycle 7 Day 1
Population: Number of Participants Analyzed included all participants in the plasma CNA analysis population within each treatment group at screening. Number Analyzed included all participants in the plasma CNA analysis population within each treatment group at the specified visit.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Lorlatinib | 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 | Cycle 7 Day 1 | EML4-ALK Variant 1 | 0 Participants |
| Lorlatinib | 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 | Cycle 2 Day 1 | EML4-ALK Variant 2 | 2 Participants |
| Lorlatinib | 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 | Cycle 2 Day 1 | EML4-ALK Variant 3 | 2 Participants |
| Lorlatinib | 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 | Cycle 2 Day 1 | EML4-ALK Other | 2 Participants |
| Lorlatinib | 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 | Cycle 7 Day 1 | ALK Rearrangement Not Detected | 48 Participants |
| Lorlatinib | 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 | Cycle 7 Day 1 | No cfDNA Detected | 52 Participants |
| Lorlatinib | 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 | at Screening | EML4-ALK Variant 1 | 19 Participants |
| Lorlatinib | 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 | at Screening | EML4-ALK Variant 3 | 18 Participants |
| Lorlatinib | 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 | at Screening | EML4-ALK Other | 15 Participants |
| Lorlatinib | 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 | at Screening | ALK Rearrangement Other | 2 Participants |
| Lorlatinib | 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 | at Screening | ALK Rearrangement Not Detected | 32 Participants |
| Lorlatinib | 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 | at Screening | No cfDNA Detected | 32 Participants |
| Lorlatinib | 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 | at Screening | Other (Sample failed analysis, uninformative, or not analyzed.) | 5 Participants |
| Lorlatinib | 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 | Cycle 2 Day 1 | EML4-ALK Variant 1 | 1 Participants |
| Lorlatinib | 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 | Cycle 2 Day 1 | ALK Rearrangement Other | 0 Participants |
| Lorlatinib | 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 | Cycle 2 Day 1 | ALK Rearrangement Not Detected | 61 Participants |
| Lorlatinib | 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 | Cycle 2 Day 1 | No cfDNA Detected | 53 Participants |
| Lorlatinib | 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 | Cycle 2 Day 1 | Other (Sample failed analysis, uninformative, or not analyzed.) | 4 Participants |
| Lorlatinib | 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 | at Screening | EML4-ALK Variant 2 | 7 Participants |
| Lorlatinib | 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 | Cycle 7 Day 1 | EML4-ALK Variant 2 | 0 Participants |
| Lorlatinib | 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 | Cycle 7 Day 1 | EML4-ALK Variant 3 | 0 Participants |
| Lorlatinib | 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 | Cycle 7 Day 1 | EML4-ALK Other | 0 Participants |
| Lorlatinib | 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 | Cycle 7 Day 1 | ALK Rearrangement Other | 0 Participants |
| Lorlatinib | 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 | Cycle 7 Day 1 | Other (Sample failed analysis, uninformative, or not analyzed.) | 3 Participants |
| Crizotinib | 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 | Cycle 7 Day 1 | Other (Sample failed analysis, uninformative, or not analyzed.) | 2 Participants |
| Crizotinib | 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 | at Screening | EML4-ALK Variant 2 | 2 Participants |
| Crizotinib | 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 | Cycle 2 Day 1 | EML4-ALK Variant 1 | 7 Participants |
| Crizotinib | 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 | Cycle 2 Day 1 | EML4-ALK Variant 2 | 0 Participants |
| Crizotinib | 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 | Cycle 2 Day 1 | EML4-ALK Variant 3 | 2 Participants |
| Crizotinib | 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 | Cycle 7 Day 1 | EML4-ALK Variant 2 | 1 Participants |
| Crizotinib | 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 | Cycle 2 Day 1 | EML4-ALK Other | 1 Participants |
| Crizotinib | 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 | Cycle 2 Day 1 | ALK Rearrangement Other | 0 Participants |
| Crizotinib | 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 | Cycle 7 Day 1 | ALK Rearrangement Not Detected | 34 Participants |
| Crizotinib | 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 | Cycle 7 Day 1 | ALK Rearrangement Other | 2 Participants |
| Crizotinib | 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 | Cycle 2 Day 1 | ALK Rearrangement Not Detected | 48 Participants |
| Crizotinib | 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 | at Screening | EML4-ALK Variant 1 | 25 Participants |
| Crizotinib | 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 | Cycle 7 Day 1 | EML4-ALK Variant 3 | 4 Participants |
| Crizotinib | 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 | at Screening | EML4-ALK Variant 3 | 21 Participants |
| Crizotinib | 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 | Cycle 2 Day 1 | No cfDNA Detected | 58 Participants |
| Crizotinib | 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 | at Screening | EML4-ALK Other | 9 Participants |
| Crizotinib | 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 | Cycle 7 Day 1 | No cfDNA Detected | 35 Participants |
| Crizotinib | 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 | at Screening | ALK Rearrangement Other | 4 Participants |
| Crizotinib | 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 | Cycle 2 Day 1 | Other (Sample failed analysis, uninformative, or not analyzed.) | 2 Participants |
| Crizotinib | 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 | at Screening | ALK Rearrangement Not Detected | 36 Participants |
| Crizotinib | 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 | Cycle 7 Day 1 | EML4-ALK Other | 1 Participants |
| Crizotinib | 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 | at Screening | No cfDNA Detected | 25 Participants |
| Crizotinib | 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 | Cycle 7 Day 1 | EML4-ALK Variant 1 | 5 Participants |
| Crizotinib | 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 | at Screening | Other (Sample failed analysis, uninformative, or not analyzed.) | 3 Participants |
Secondary
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.
Time frame: From Baseline up to 33 months
Population: Number of Participants Analyzed included all participants in the safety analysis population. Number Analyzed included all participants in the safety analysis population with evaluable data against the pre-defined criteria.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | Change of QTcF <30 msec | 92 Participants |
| Lorlatinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | 30 msec ≤ Change of QTcF <60 msec | 49 Participants |
| Lorlatinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | PR change ≥50% if absolute baseline value was <200 msec | 8 Participants |
| Lorlatinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | Change of QTcB ≥60 msec | 10 Participants |
| Lorlatinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | PR change ≥25% if absolute baseline value was ≥200 msec | 0 Participants |
| Lorlatinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | Change of QTcF ≥60 msec | 5 Participants |
| Lorlatinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | QRS change ≥50% if absolute baseline value was <100 msec | 2 Participants |
| Lorlatinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | 30 msec ≤ Change of QTcB <60 msec | 49 Participants |
| Lorlatinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | QRS change ≥25% if absolute baseline value was ≥100 msec | 2 Participants |
| Lorlatinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | Change of QTcB <30 msec | 90 Participants |
| Crizotinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | QRS change ≥25% if absolute baseline value was ≥100 msec | 0 Participants |
| Crizotinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | Change of QTcF ≥60 msec | 16 Participants |
| Crizotinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | 30 msec ≤ Change of QTcF <60 msec | 41 Participants |
| Crizotinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | Change of QTcF <30 msec | 81 Participants |
| Crizotinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | Change of QTcB ≥60 msec | 15 Participants |
| Crizotinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | 30 msec ≤ Change of QTcB <60 msec | 26 Participants |
| Crizotinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | Change of QTcB <30 msec | 100 Participants |
| Crizotinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | PR change ≥50% if absolute baseline value was <200 msec | 4 Participants |
| Crizotinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | PR change ≥25% if absolute baseline value was ≥200 msec | 0 Participants |
| Crizotinib | Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria | QRS change ≥50% if absolute baseline value was <100 msec | 3 Participants |
Secondary
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%.
Time frame: From Baseline up to 33 months
Population: Number of Participants Analyzed included all participants in the safety analysis population. Number Analyzed included all participants in the safety analysis population with evaluable data against the pre-defined criteria.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting pulse rate: pulse <50 bpm | 4 Participants |
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting systolic blood pressure: change ≥40 mmHg decrease | 6 Participants |
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting diastolic blood pressure: change ≥40 mmHg decrease | 0 Participants |
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting systolic blood pressure: change ≥60 mmHg decrease | 0 Participants |
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting pulse rate: change ≥30 bpm increase | 24 Participants |
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting diastolic blood pressure: change ≥20 mmHg decrease | 26 Participants |
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting pulse rate: pulse >120 bpm | 7 Participants |
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Body weight (kg): percent change from baseline ≥10% increase | 99 Participants |
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting pulse rate: change ≥30 bpm decrease | 17 Participants |
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Body weight (kg): percent change from baseline ≥20% increase | 35 Participants |
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting diastolic blood pressure: change ≥20 mmHg increase | 41 Participants |
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Body weight (kg): percent change from baseline ≥10% decrease | 6 Participants |
| Lorlatinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting systolic blood pressure: change ≥40 mmHg increase | 22 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Body weight (kg): percent change from baseline ≥10% decrease | 12 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting diastolic blood pressure: change ≥20 mmHg decrease | 52 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting pulse rate: pulse >120 bpm | 1 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting pulse rate: pulse <50 bpm | 22 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting pulse rate: change ≥30 bpm increase | 3 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting pulse rate: change ≥30 bpm decrease | 47 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting systolic blood pressure: change ≥40 mmHg increase | 3 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting systolic blood pressure: change ≥40 mmHg decrease | 14 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting diastolic blood pressure: change ≥20 mmHg increase | 18 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting diastolic blood pressure: change ≥40 mmHg decrease | 1 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Body weight (kg): percent change from baseline ≥10% increase | 39 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Body weight (kg): percent change from baseline ≥20% increase | 3 Participants |
| Crizotinib | Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria | Sitting systolic blood pressure: change ≥60 mmHg decrease | 1 Participants |
Secondary
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.
Time frame: From time of Study Start up to 33 months
Population: The FA population included all participants who were randomized, and participants were classified according to the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lorlatinib | Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on BICR Assessment | 75.8 Percentage of participants |
| Crizotinib | Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on BICR Assessment | 57.8 Percentage of participants |
p-value: 0.000595% CI: [1.353, 3.891]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: From time of Study Start up to 33 months
Population: The FA population included all participants who were randomized, and participants were classified according to the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lorlatinib | Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on Investigator's Assessment | 80.5 Percentage of participants |
| Crizotinib | Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on Investigator's Assessment | 61.9 Percentage of participants |
p-value: 0.000295% CI: [1.484, 4.594]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: From time of Study Start up to 33 months
Population: The FA population included all participants who were randomized, and participants were classified according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Overall Survival (OS) | NA Months |
| Crizotinib | Overall Survival (OS) | NA Months |
95% CI: [0.414, 1.249]
Secondary
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
Time frame: From time of Study Start up to 45 months
Secondary
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.
Time frame: From time of Study Start up to 33 months
Population: The FA population included all participants who were randomized, and participants were classified according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Progression-Free Survival (PFS) Based on Investigator's Assessment | NA Months |
| Crizotinib | Progression-Free Survival (PFS) Based on Investigator's Assessment | 9.1 Months |
p-value: <0.000195% CI: [0.144, 0.307]one-sided stratified log-rank
Secondary
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.
Time frame: From Baseline up to 33 months
Population: Participants in the EORTC QLQ-LC13 PRO analysis population with change from baseline scores within each treatment group and subscale.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Time to Deterioration (TTD) in Participant Reported Pain in Chest, Dyspnea, or Cough From QLQ-LC13 | 3.3 Months |
| Crizotinib | Time to Deterioration (TTD) in Participant Reported Pain in Chest, Dyspnea, or Cough From QLQ-LC13 | 3.7 Months |
p-value: 0.729395% CI: [0.822, 1.444]one-sided stratified log-rank
Secondary
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.
Time frame: From time of Study Start up to 33 months
Population: Participants with confirmed complete response or partial response in the FA population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Time to Tumor Response (TTR) Based on BICR Assessment | 1.8 Months |
| Crizotinib | Time to Tumor Response (TTR) Based on BICR Assessment | 1.8 Months |