Clinical Trial Results:
Single-Arm Study of Lorlatinib in Participants With Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer (NSCLC) Whose Disease Progressed After one Prior Second-Generation ALK Tyrosine Kinase Inhibitor (TKI)
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Summary
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EudraCT number |
2019-002504-41 |
Trial protocol |
PL GB IT |
Global end of trial date |
23 Oct 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Oct 2025
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First version publication date |
29 Oct 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
B7461027
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04362072 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pfizer Inc.
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Sponsor organisation address |
66 Hudson Boulevard East, New York, United States, NY 10001-2192
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 Feb 2025
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Oct 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess overall and intracranial response rate of single agent Lorlatinib in participants with advanced ALK positive NSCLC whose disease has progressed on alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trials participants were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Sep 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 33
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Country: Number of subjects enrolled |
Spain: 18
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Country: Number of subjects enrolled |
India: 11
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Country: Number of subjects enrolled |
Poland: 3
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Country: Number of subjects enrolled |
Switzerland: 2
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Country: Number of subjects enrolled |
United Kingdom: 2
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Country: Number of subjects enrolled |
United States: 2
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Worldwide total number of subjects |
71
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EEA total number of subjects |
54
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
48
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From 65 to 84 years |
22
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85 years and over |
1
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Recruitment
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Recruitment details |
A total of 71 participants were enrolled in the study. | ||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Participants were enrolled at multiple sites, where study started from 29 September 2020 and completed on 23 October 2024. | ||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||
Blinding implementation details |
There was no blinding.
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Arms
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Arm title
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Lorlatinib | ||||||||||||||||||||||||||
Arm description |
Participants received Lorlatinib 100 milligrams (mg) (25 mg*4 tablets) orally once daily (QD) in 21-day cycles. Participants continued to receive study treatment until objective disease progression, unacceptable toxicity, participant refusal, lost to follow up or death, whichever occurred first. | ||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||
Investigational medicinal product name |
Lorlatinib
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Investigational medicinal product code |
PF-06463922
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received Lorlatinib 100 mg orally once daily in 21-day cycle.
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Baseline characteristics reporting groups
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Reporting group title |
Overall study
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Reporting group description |
Participants received Lorlatinib 100 mg (25 mg*4 tablets) orally QD in 21-day cycles. Participants continued to receive study treatment until objective disease progression, unacceptable toxicity, participant refusal, lost to follow up or death, whichever occurred first. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lorlatinib
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Reporting group description |
Participants received Lorlatinib 100 milligrams (mg) (25 mg*4 tablets) orally once daily (QD) in 21-day cycles. Participants continued to receive study treatment until objective disease progression, unacceptable toxicity, participant refusal, lost to follow up or death, whichever occurred first. | ||
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End point title |
Percentage of Participants With Confirmed Objective Response (OR) as per Independent Central Review (ICR) as Assessed by RECIST v1.1 [1] | ||||||||
End point description |
Confirmed OR based on ICR assessment was defined as complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumor (RECIST) version(v)1.1 from date of first dose until documented progressive disease(PD) or start of new anti-cancer therapy without regard to discontinuation from treatment. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after criteria for response are first met. CR: disappearance of all target and non-target(NT) lesions. PR: at least 30% decrease in sum of diameters of target, taking as reference baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. Appearance of one or more new lesions was also considered sign of progression. For non-target PD: unequivocal progression of existing non-target lesions. Intent to treat (ITT) analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.
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End point type |
Primary
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End point timeframe |
From date of first dose until documented PD or start of new anti-cancer therapy, whichever occurred earlier (maximum treatment exposure up to 42.78 months)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Confirmed Intracranial (IC) Objective Response (IC-OR) as per ICR as Assessed by RECIST v 1.1 | ||||||||
End point description |
IC-OR based on ICR assessment: IC-CR/PR according to RECISTv1.1 from date of first dose until documented IC-PD/start of new anti-cancer therapy without regard to discontinuation from treatment. Both IC-CR and IC-PR must be confirmed by repeat assessments performed no <4 weeks after criteria for response first met. IC-CR: disappearance of all target and non-target lesions. IC-PR:at least 30% decrease in sum of diameters of IC target lesions, taking reference baseline sum diameters. PD:at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. Appearance of one/more new IC lesions was also considered sign of progression. For non-target IC-PD: unequivocal progression of existing IC-non-target lesions. Per-protocol analysis population based on ICR(PPICR) included all enrolled participants who took at least 1 dose of Lorlatinib, had central nervous system(CNS)metastases at study entry(i.e. with lesions having disease site=brain)according to ICR.
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End point type |
Secondary
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End point timeframe |
From date of first dose until documented PD or start of new anti-cancer therapy, whichever occurred earlier (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Confirmed OR as per Investigator (INV) as Assessed by RECIST v 1.1 | ||||||||
End point description |
Confirmed OR based on derived investigator assessment was defined as CR or PR according to RECIST v1.1 from date of first dose until PD or start of new anti-cancer therapy without regard to discontinuation from treatment. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after criteria for response are first met. CR: disappearance of all target and non-target lesions. PR: at least 30 % decrease in sum of diameters of target, taking as reference baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. Appearance of one or more new lesions was also considered sign of progression. For non-target PD: unequivocal progression of existing non-target lesions. ITT analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.
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End point type |
Secondary
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End point timeframe |
From date of first dose until documented PD or start of new anti-cancer therapy, whichever occurred earlier (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Response (TTR) as per ICR as Assessed by RECIST v 1.1 | ||||||||
End point description |
TTR based on ICR assessments was defined, for participants with a confirmed OR, as the time from the date of first dose to the first documentation of OR (CR or PR) which was subsequently confirmed. For participants whose OR proceeded from PR to CR, the onset of PR was taken as the onset of response. CR: disappearance of all target and non-target lesions. PR: at least 30 % decrease in sum of diameters of target, taking as reference baseline sum diameters. Analysis population included all enrolled participants who took at least 1 dose of Lorlatinib and had confirmed CR or PR as per ICR.
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End point type |
Secondary
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End point timeframe |
From date of first dose until first documented objective response, CR or PR (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
TTR as per INV as Assessed by RECIST v 1.1 | ||||||||
End point description |
TTR based on derived investigator assessments was defined, for participants with a confirmed objective response, as the time from the date of first dose to the first documentation of objective response (CR or PR) which is subsequently confirmed. For participants whose OR proceeds from PR to CR, the onset of PR is taken as the onset of response. CR: disappearance of all target (T) and non-target lesions. PR: at least 30 % decrease in sum of diameters of target, taking as reference baseline sum diameters. Analysis population included all enrolled participants who took at least 1 dose of Lorlatinib and had confirmed CR or PR as per INV.
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End point type |
Secondary
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End point timeframe |
From date of first dose until first documented objective response, CR or PR (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response (DOR) as per ICR as Assessed by RECIST v 1.1 | ||||||||
End point description |
DOR: as time from first documentation of OR per ICR(CR/PR whichever was earlier) to date of first documentation of PD/death due to any cause, whichever came first. CR: disappearance of all target and non-target lesions.PR:at least 30% decrease in sum of diameters of target,taking as reference baseline sum diameters. PD:at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. Appearance of >=1 new lesions:sign of progression.For non-target PD:unequivocal progression of existing non-target lesions.Participants who completed/discontinued study without PD/death, as well as who received alternate anti-cancer therapy prior to PD, were censored at last adequate response assessment date/last adequate assessment prior to start date of alternate anti-cancer therapy. Kaplan-Meier method used. Participants who took at least 1 dose of Lorlatinib with confirmed CR/ PR as per ICR. 99999:Median and 95%CI upper limit inestimable due to insufficient data.
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End point type |
Secondary
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End point timeframe |
From first documented OR (CR or PR) to date of first documented PD or death due to any cause or censoring date, whichever occurred first (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Confirmed IC-OR as per INV as Assessed by RECIST v 1.1 | ||||||||
End point description |
IC-OR based on derived investigator assessment:IC-CR/PR according to RECISTv1.1 from date of first dose until documented IC-PD/start of new anti-cancer therapy without regard to discontinuation from treatment.Both IC-CR and IC-PR must be confirmed by repeat assessments performed no <4 weeks after criteria for response first met. IC-CR: disappearance of all target and non-target lesions. IC-PR:at least 30% decrease in sum of diameters of IC target lesions, taking reference baseline sum diameters. PD:at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. Appearance of one/more new IC lesions was also considered sign of progression. For non-target IC-PD: unequivocal progression of existing IC-non-target lesions. Per-protocol analysis population based on INV(PPINV) included all enrolled participants who took at least 1 dose of Lorlatinib,had CNS metastases at study entry(i.e. with lesions having disease site=brain)according to investigator.
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End point type |
Secondary
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End point timeframe |
From date of first dose until documented PD or start of new anti-cancer therapy, whichever occurred earlier (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Intracranial Response (IC-DoR) as per ICR as Assessed by RECIST v 1.1 | ||||||||
End point description |
IC-DoR:for participants with confirmed objective intra-cranial response per ICR,as time from first documentation of objective intra-cranial response to date of first documentation of PD in brain/death due to any cause,whichever occurs first. IC-CR:disappearance of all T & NT lesions. IC-PR: at least 30%decrease in sum of diameters of T,taking as reference baseline sum diameter. IC-PD:at least 20%increase in sum of diameters of T lesions, taking reference smallest sum on study/appearance of new IC lesions. IC-NT PD:unequivocal progression of existing IC-NT lesions.Participants who completed/discontinued study without PD/death,who received alternate anti-cancer therapy prior to IC-PD,were censored at last adequate response assessment date/last adequate assessment prior to start date of alternate anti-cancer therapy.Analysis:Kaplan-Meier. Subjects analyzed=no. of participants evaluable for endpoint.PPICR used.99999=Median,upper,lower limit of 95%CI not estimable due to insufficient data.
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End point type |
Secondary
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End point timeframe |
From first documented IC-OR (CR or PR) to date of first documented PD or death due to any cause or censoring date, whichever occurred first (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
DOR as per INV as Assessed by RECIST v 1.1 | ||||||||
End point description |
DOR: as time from first documentation of OR per INV (CR/PR whichever was earlier) to date of first documentation of PD/death due to any cause, whichever came first. CR: disappearance of all target and non-target lesions.PR:at least 30% decrease in sum of diameters of target,taking as reference baseline sum diameters. PD:at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. Appearance of >=1 new lesions: sign of progression. For non-target PD:unequivocal progression of existing non-target lesions. Participants who completed/discontinued study without PD/death, as well as who received alternate anti-cancer therapy prior to PD, were censored at their last adequate response assessment date/last adequate assessment prior to start date of alternate anti-cancer therapy. Kaplan-Meier method used. Participants who took at least 1 dose of Lorlatinib with confirmed CR/PR as per INV. 99999: Upper limit of 95% inestimable due to insufficient data.
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End point type |
Secondary
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End point timeframe |
From first documented OR (CR or PR) to date of first documented PD or death due to any cause or censoring date, whichever occurred first (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
IC-DoR as per INV as Assessed by RECIST v 1.1 | ||||||||
End point description |
IC-DoR:for participants with confirmed objective intra-cranial response per INV,as time from first documentation of objective intra-cranial response to date of first documentation of PD in brain/death due to any cause,whichever occurs first. IC-CR:disappearance of all T & NT lesions. IC-PR:at least 30%decrease in sum of diameters of T,taking as reference baseline sum diameter. IC-PD:at least 20%increase in sum of diameters of T lesions, taking reference smallest sum on study/appearance of new IC lesions. IC-NT PD:unequivocal progression of existing IC-NT lesions.Participants who completed/discontinued study without PD/death,who received alternate anti-cancer therapy prior to IC-PD,were censored at last adequate response assessment date/last adequate assessment prior to start date of alternate anti-cancer therapy. Analysis:Kaplan-Meier. Subjects analyzed=no.of participants evaluable for endpoint.PPINV used.99999=Median,upper,lower limit of 95%CI not estimable due to insufficient data.
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End point type |
Secondary
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End point timeframe |
From first documented IC-OR (CR or PR) to date of first documented PD or death due to any cause or censoring date, whichever occurred first (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Tumor Progression (TTP) as per ICR as Assessed by RECIST v 1.1 | ||||||||
End point description |
TTP according to RECIST v1.1 as time from date of first dose to the date of the first documentation of PD per IRC. PD was defined as at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. Appearance of one or more new lesions was also considered sign of progression. For non-target PD: unequivocal progression of existing non-target lesions. Participants who completed or discontinued study without PD or death, as well as participants who received alternate anti-cancer therapy prior to PD, were censored at their last adequate response assessment date or last adequate assessment prior to start date of alternate anti-cancer therapy. Analysis was performed using Kaplan-Meier method. ITT analysis population included all enrolled participants who took at least 1 dose of Lorlatinib. Here, 99999= Upper limit of 95% CI is not estimable due to insufficient data.
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End point type |
Secondary
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End point timeframe |
From date of first dose until first documented PD or censoring date, whichever occurred first (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
TTP as per INV as Assessed by RECIST v 1.1 | ||||||||
End point description |
TTP according to RECIST v1.1 as time from date of first dose to the date of the first documentation of PD per investigator. PD was defined as at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. Appearance of one or more new lesions was also considered sign of progression. For non-target PD: unequivocal progression of existing non-target lesions. Participants who completed or discontinued study without PD or death, as well as participants who received alternate anti-cancer therapy prior to PD, were censored at their last adequate response assessment date or last adequate assessment prior to start date of alternate anti-cancer therapy. Analysis was performed using Kaplan-Meier method. ITT analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.
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End point type |
Secondary
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End point timeframe |
From date of first dose until first documented PD or censoring date, whichever occurred first (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-Free Survival (PFS) as per ICR as Assessed by RECIST v 1.1 | ||||||||
End point description |
PFS according to RECIST v1.1 was defined as the time from date of first dose to the date of the first documentation of PD per ICR or death due to any cause, whichever occurred first. PD was defined as at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. Appearance of one or more new lesions was also considered sign of progression. For non-target PD: unequivocal progression of existing non-target lesions. Participants who completed or discontinued study without PD or death, as well as participants who received alternate anti-cancer therapy prior to PD, were censored at their last adequate response assessment date or last adequate assessment prior to start date of alternate anti-cancer therapy. Analysis was performed using Kaplan-Meier method. ITT analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.
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End point type |
Secondary
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End point timeframe |
From date of first dose until first documented PD or death or censoring date, whichever occurred first (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
PFS as per INV as Assessed by RECIST v 1.1 | ||||||||
End point description |
PFS according to RECIST v1.1 was defined as the time from date of first dose to the date of the first documentation of PD per INV or death due to any cause, whichever occurred first. PD was defined as at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. Appearance of one or more new lesions was also considered sign of progression. For non-target PD: unequivocal progression of existing non-target lesions. Participants who completed or discontinued study without PD or death, as well as participants who received alternate anti-cancer therapy prior to PD, were censored at their last adequate response assessment date or last adequate assessment prior to start date of alternate anti-cancer therapy. Analysis was performed using Kaplan-Meier method. ITT analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.
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End point type |
Secondary
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End point timeframe |
From date of first dose until first documented PD or death or censoring date, whichever occurred first (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
IC-TTR as per INV as Assessed by RECIST v 1.1 | ||||||||
End point description |
IC-TTR: for participants with a confirmed IC-OR per investigator, was defined as the time from the date of first dose to the first documentation of objective intra-cranial response (CR or PR) which is subsequently confirmed. For participants whose IC-OR proceeds from PR to CR, the onset of PR was taken as the onset of response. IC-CR: disappearance of all target and non-target lesions. IC-PR: at least 30 % decrease in sum of diameters of target, taking as reference baseline sum diameters. Here subjects analyzed signifies number of participants evaluable for this endpoint. PPINV included all enrolled participants who took at least 1 dose of Lorlatinib and had CNS metastases at study entry (i.e. with lesions having disease site = brain) according to investigator.
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End point type |
Secondary
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End point timeframe |
From date of first dose to the first documented objective intra-cranial response (CR or PR) (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Intra-Cranial Response (IC-TTR) as per ICR as Assessed by RECIST v 1.1 | ||||||||
End point description |
IC-TTR: for participants with a confirmed IC-OR per ICR, was defined as the time from the date of first dose to the first documentation of objective intra-cranial response (CR or PR) which is subsequently confirmed. For participants whose IC-OR proceeds from PR to CR, the onset of PR was taken as the onset of response. IC-CR: disappearance of all target and non-target lesions. IC-PR: at least 30 % decrease in sum of diameters of target, taking as reference baseline sum diameters. Here subjects analyzed signifies number of participants evaluable for this endpoint. PPICR included all enrolled participants who took at least 1 dose of Lorlatinib and had CNS metastases at study entry (i.e. with lesions having disease site = brain) according to ICR.
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End point type |
Secondary
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End point timeframe |
From date of first dose to the first documented objective intra-cranial response (CR or PR) (maximum treatment exposure up to 42.78 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) | ||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in participant or clinical study participant, temporally associated with use of study intervention, whether or not considered related to study intervention. A TEAE was defined as any event that occurs for first time during on-treatment period or AEs that were observed prior to start of study treatment but increased in severity during on-treatment period (defined as time from first dose of study treatment through end of safety follow-up period, ie at least 28 days, and no more than 35 days after discontinuation of treatment, or start of new anti-cancer therapies [follow up systemic therapy, follow up radiation therapy or follow-up surgery], whichever occurs first). Adverse events occurring on same day as first dose of study treatment were also considered to have occurred during the on-treatment period. Safety analysis set included all enrolled participants who took at least 1 dose of study intervention.
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End point type |
Secondary
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End point timeframe |
From first dose of the study treatment (Day 1) maximum up to 28-35 days after last dose of study drug or the new anti-cancer therapy date, whichever is earlier (maximum treatment exposure up to 43.78 months)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants With Treatment-Related TEAEs | ||||||
End point description |
An AE was any untoward medical occurrence in participant or clinical study participant, temporally associated with use of study intervention, considered related to study intervention. A TEAE was defined as any event that occurs for first time during on-treatment period/ AEs that were observed prior to start of study treatment but increased in severity during on-treatment period (defined as time from first dose of study treatment through end of safety follow-up period, ie at least 28 days, and no more than 35 days after discontinuation of treatment, or start of new anti-cancer therapies [follow up systemic therapy, follow up radiation therapy or follow-up surgery], whichever occurs first). Adverse events occurring on same day as first dose of study treatment were also considered to have occurred during the on-treatment period. An AE was considered treatment related if investigator considered event related to study drugs/ information was unknown. Safety analysis set used.
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End point type |
Secondary
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End point timeframe |
From first dose of the study treatment (Day 1) maximum up to 28-35 days after last dose of study drug or the new anti-cancer therapy date, whichever is earlier (maximum treatment exposure up to 43.78 months)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants With Maximum Grade 3 or 4 TEAEs by National Cancer Institute Common Terminology Criteria for AEs [NCI CTCAE] v.4.03 | ||||||
End point description |
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with use of study intervention, whether or not considered related to study intervention. A TEAE was defined as any event that occurs for first time during on-treatment period or AEs that were observed prior to start of study treatment but increased in severity during on-treatment period (defined as time from first dose of study treatment through end of safety follow-up period, ie at least 28 days, and no more than 35 days after discontinuation of treatment, or start of new anti-cancer therapies, whichever occurs first). Adverse events occurring on same day as first dose of study treatment were also considered to have occurred during the on-treatment period. TEAEs were graded according to NCI CTCAE v4.03 as grade 3= severe AE and grade 4= life threatening consequences; urgent intervention indicated. Safety analysis set used.
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End point type |
Secondary
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End point timeframe |
From first dose of the study treatment (Day 1) maximum up to 28-35 days after last dose of study drug or the new anti-cancer therapy date, whichever is earlier (maximum treatment exposure up to 43.78 months)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants With Maximum Grade 3 or 4 Treatment-Related AEs | ||||||
End point description |
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with use of study intervention, considered related to study intervention. An AE was considered treatment related if investigator considered event related to study drugs or the information was unknown. TEAEs were graded according to CTCAE v4.03 as grade 3= severe AE and grade 4= life threatening consequences. Safety analysis set included all enrolled participants who took at least 1 dose of study intervention.
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End point type |
Secondary
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End point timeframe |
From first dose of the study treatment (Day 1) maximum up to 28-35 days after last dose of study drug or the new anti-cancer therapy date, whichever is earlier (maximum treatment exposure up to 43.78 months)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) | ||||||
End point description |
A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) or resulted in congenital anomaly/birth defect or was considered an important medical event. TESAEs were defined as any event that occurs for first time during on-treatment period or SAEs that were observed prior to start of study treatment but increased in severity during on-treatment period (defined as time from first dose of study treatment through end of safety follow-up period, ie at least 28 days, and no more than 35 days after discontinuation of treatment, or start of new anti-cancer therapies, whichever occurs first). Safety analysis set included all enrolled participants who took at least 1 dose of study intervention.
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End point type |
Secondary
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End point timeframe |
From first dose of the study treatment (Day 1) maximum up to 28-35 days after last dose of study drug or the new anti-cancer therapy date, whichever is earlier (maximum treatment exposure up to 43.78 months)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of participants With Treatment-Related TESAEs | ||||||
End point description |
SAE was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions)/ resulted in congenital anomaly/birth defect/ was considered an important medical event. TESAEs: any event that occurs for first time during on-treatment period/ SAEs that were observed prior to start of study treatment but increased in severity during on-treatment period (defined as time from first dose of study treatment through end of safety follow-up period, ie at least 28 days, and no more than 35 days after discontinuation of treatment/ start of new anti-cancer therapies, whichever occurs first). SAE was considered treatment related if investigator considered event related to study drugs or information was unknown. Safety analysis set used.
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End point type |
Secondary
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End point timeframe |
From first dose of the study treatment (Day 1) maximum up to 28-35 days after last dose of study drug or the new anti-cancer therapy date, whichever is earlier (maximum treatment exposure up to 43.78 months)
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of the study treatment (Day 1) maximum up to 28-35 days after last dose of study drug or the new anti-cancer therapy date, whichever was earlier (maximum treatment exposure up to 43.78 months)
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Adverse event reporting additional description |
Safety analysis set. Same event may appear as both non-SAE & SAE. Presented are distinct events. Event may be categorized: serious in 1 participant and non-serious in other/may have experienced both SAE & non-SAE.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
v27.1
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Reporting groups
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Reporting group title |
Lorlatinib
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Reporting group description |
Participants received Lorlatinib 100 mg (25 mg*4 tablets) orally QD in 21-day cycles. Participants continued to receive study treatment until objective disease progression, unacceptable toxicity, participant refusal, lost to follow up or death, whichever occurred first. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Sep 2022 |
Permitted participants meeting criteria who continued to experience clinical benefit from the study intervention to continue therapy after disease progression and to provide clarity around reasons for discontinuation of study intervention. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
