Trial Outcomes & Findings for Study of Lorlatinib In People With ALK-positive Non-small Cell Lung Cancer (NCT NCT04362072)
NCT ID: NCT04362072
Last Updated: 2025-06-11
Results Overview
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 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. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 millimeter (mm). Appearance of one or more new lesions was also considered sign of progression. For non-target PD: unequivocal progression of existing non-target lesions.
COMPLETED
PHASE4
71 participants
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)
2025-06-11
Participant Flow
Participant milestones
| Measure |
Lorlatinib
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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Treatment
STARTED
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71
|
|
Treatment
COMPLETED
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0
|
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Treatment
NOT COMPLETED
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71
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|
Follow up
STARTED
|
35
|
|
Follow up
COMPLETED
|
31
|
|
Follow up
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Lorlatinib
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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|---|---|
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Treatment
Adverse Event
|
1
|
|
Treatment
Death
|
9
|
|
Treatment
Physician Decision
|
2
|
|
Treatment
Progressive disease
|
27
|
|
Treatment
Withdrawal by Subject
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4
|
|
Treatment
Global deterioration of health status
|
1
|
|
Treatment
Switched to commercial Lorlatinib
|
13
|
|
Treatment
Entered Lorlatinib continuation Study
|
11
|
|
Treatment
Other
|
3
|
|
Follow up
Death
|
2
|
|
Follow up
Other
|
2
|
Baseline Characteristics
Study of Lorlatinib In People With ALK-positive Non-small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Lorlatinib
n=71 Participants
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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|---|---|
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Age, Continuous
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58.14 Years
STANDARD_DEVIATION 12.93 • n=5 Participants
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Sex: Female, Male
Female
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30 Participants
n=5 Participants
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Sex: Female, Male
Male
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41 Participants
n=5 Participants
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Race/Ethnicity, Customized
Race · Asian
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15 Participants
n=5 Participants
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Race/Ethnicity, Customized
Race · White
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54 Participants
n=5 Participants
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|
Race/Ethnicity, Customized
Race · Unknown or Not Reported
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2 Participants
n=5 Participants
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PRIMARY outcome
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)Population: Intent to treat (ITT) analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.
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 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. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 millimeter (mm). Appearance of one or more new lesions was also considered sign of progression. For non-target PD: unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Lorlatinib
n=71 Participants
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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|---|---|
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Percentage of Participants With Confirmed Overall Objective Response (OR) as Per Independent Central Review (ICR) as Assessed by RECIST v1.1
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42.3 Percentage of participants
Interval 30.6 to 54.6
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SECONDARY outcome
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)Population: ITT analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.
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. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered sign of progression. For non-target PD: unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Lorlatinib
n=71 Participants
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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|---|---|
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Percentage of Participants With Confirmed OR as Per Investigator (INV) as Assessed by RECIST v 1.1
|
36.6 Percentage of participants
Interval 25.5 to 48.9
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SECONDARY outcome
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)Population: Per-protocol analysis population based on ICR (PPICR) included all enrolled participants who took at least 1 dose of Lorlatinib and had central nervous system (CNS) metastases at study entry (i.e. with lesions having disease site = brain) according to ICR.
IC-OR based on ICR assessment was defined as IC-CR or PR according to RECIST v1.1 from date of first dose until documented IC-PD or 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 less than 4 weeks after the 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. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered sign of progression. For non-target PD: unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Lorlatinib
n=30 Participants
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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|---|---|
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Percentage of Participants With Confirmed Intracranial (IC) Objective Response (IC-OR) as Per ICR as Assessed by RECIST v 1.1
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46.7 Percentage of participants
Interval 28.3 to 65.7
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SECONDARY outcome
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)Population: Per-protocol analysis population based on (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.
IC-OR based on derived investigator assessment was defined as IC-CR or PR according to RECIST v1.1 from date of first dose until documented IC-PD or 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 less than 4 weeks after the 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. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered sign of progression. For non-target PD: unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Lorlatinib
n=23 Participants
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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|---|---|
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Percentage of Participants With Confirmed IC-OR as Per INV as Assessed by RECIST v 1.1
|
56.5 Percentage of participants
Interval 34.5 to 76.8
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SECONDARY outcome
Timeframe: From date of first dose until first documented objective response, CR or PR (maximum treatment exposure up to 42.78 months)Population: Analysis population included all enrolled participants who took at least 1 dose of Lorlatinib and had confirmed CR or PR as per ICR.
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.
Outcome measures
| Measure |
Lorlatinib
n=30 Participants
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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|---|---|
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Time to Response (TTR) as Per ICR as Assessed by RECIST v 1.1
|
1.5 Months
Interval 1.2 to 8.4
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SECONDARY outcome
Timeframe: From date of first dose until first documented objective response, CR or PR (maximum treatment exposure up to 42.78 months)Population: Analysis population included all enrolled participants who took at least 1 dose of Lorlatinib and had confirmed CR or PR as per INV.
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 and non-target lesions. PR: at least 30 % decrease in sum of diameters of target, taking as reference baseline sum diameters.
Outcome measures
| Measure |
Lorlatinib
n=26 Participants
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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|---|---|
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TTR as Per INV as Assessed by RECIST v 1.1
|
1.6 Months
Interval 1.2 to 8.3
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SECONDARY outcome
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)Population: Analysis population included all enrolled participants who took at least 1 dose of Lorlatinib and had confirmed CR or PR as per ICR.
DOR: for participants with confirmed OR per ICR, as time from first documentation of OR (CR/PR whichever was earlier) to date of first documentation of PD/death due to any cause, whichever occurred 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. Addition to relative increase of 20%, sum must also demonstrate absolute increase of at least 5mm. Appearance of one/ more 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. Analysis:Kaplan-Meier method.
Outcome measures
| Measure |
Lorlatinib
n=30 Participants
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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|---|---|
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Duration of Response (DOR) as Per ICR as Assessed by RECIST v 1.1
|
NA Months
Interval 8.6 to
Median and upper limit of 95% confidence interval (CI) is not estimable due to insufficient data.
|
SECONDARY outcome
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)Population: Analysis population included all enrolled participants who took at least 1 dose of Lorlatinib and had confirmed CR or PR as per INV.
DOR: for participants with confirmed OR per investigator,as time from first documentation of OR(CR/PR whichever was earlier) to date of first documentation of PD/death due to any cause, whichever occurred 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. Addition to relative increase of 20%,sum must also demonstrate absolute increase of at least 5mm. Appearance of one/more 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. Analysis:Kaplan-Meier method.
Outcome measures
| Measure |
Lorlatinib
n=26 Participants
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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|---|---|
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DOR as Per INV as Assessed by RECIST v 1.1
|
20.9 Months
Interval 9.9 to
Upper limit of 95% CI is not estimable due to insufficient data.
|
SECONDARY outcome
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)Population: Per-protocol analysis population based on ICR (PPICR) included all enrolled participants who took at least 1 dose of Lorlatinib and had central nervous system (CNS) metastases at study entry (i.e. with lesions having disease site = brain) according to ICR. Here "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.
IC-DoR: for participants with confirmed objective intra-cranial response per ICR, as time from first documentation of objective intra-cranial response (CR/PR whichever is earlier) to date of first documentation of PD in brain or death due to any cause, whichever occurs 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 one/more new lesions: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: Kaplan-Meier method.
Outcome measures
| Measure |
Lorlatinib
n=14 Participants
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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|---|---|
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Duration of Intracranial Response (IC-DoR) as Per ICR as Assessed by RECIST v 1.1
|
NA Months
Median, upper and lower limit of 95% CI is not estimable due to insufficient data.
|
SECONDARY outcome
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)Population: Per-protocol analysis population based on (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. Here "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.
IC-DoR: for participants with confirmed objective intra-cranial response, per investigator as time from first documentation of objective intra-cranial response (CR or PR whichever is earlier) to date of first documentation of PD in brain or death due to any cause, whichever occurs 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 one/more new lesions: 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 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: Kaplan-Meier method.
Outcome measures
| Measure |
Lorlatinib
n=13 Participants
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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|---|---|
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IC-DoR as Per INV as Assessed by RECIST v 1.1
|
NA Months
Median, upper and lower limit of 95% CI is not estimable due to insufficient data.
|
SECONDARY outcome
Timeframe: From date of first dose until first documented PD or censoring date, whichever occurred first (maximum treatment exposure up to 42.78 months)Population: ITT analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.
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. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. 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.
Outcome measures
| Measure |
Lorlatinib
n=71 Participants
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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|---|---|
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Time to Tumor Progression (TTP) as Per ICR as Assessed by RECIST v 1.1
|
18.0 Months
Interval 9.7 to
Upper limit of 95% CI is not estimable due to insufficient data.
|
SECONDARY outcome
Timeframe: From date of first dose until first documented PD or censoring date, whichever occurred first (maximum treatment exposure up to 42.78 months)Population: ITT analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.
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. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. 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.
Outcome measures
| Measure |
Lorlatinib
n=71 Participants
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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|---|---|
|
TTP as Per INV as Assessed by RECIST v 1.1
|
12.2 Months
Interval 8.3 to 24.8
|
SECONDARY outcome
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)Population: ITT analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.
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. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. 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.
Outcome measures
| Measure |
Lorlatinib
n=71 Participants
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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|---|---|
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Progression-Free Survival (PFS) as Per ICR as Assessed by RECIST v 1.1
|
12.2 Months
Interval 6.9 to 22.1
|
SECONDARY outcome
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)Population: ITT analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.
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 investigator 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. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. 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.
Outcome measures
| Measure |
Lorlatinib
n=71 Participants
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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|---|---|
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PFS as Per INV as Assessed by RECIST v 1.1
|
9.7 Months
Interval 6.9 to 18.4
|
SECONDARY outcome
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)Population: PPICR included all enrolled participants who took at least 1 dose of Lorlatinib and had central nervous system (CNS) metastases at study entry (i.e. with lesions having disease site = brain) according to ICR. Here "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.
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. 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.
Outcome measures
| Measure |
Lorlatinib
n=14 Participants
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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|---|---|
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Time to Intra-Cranial Response (IC-TTR) as Per ICR as Assessed by RECIST v 1.1
|
2.8 Months
Interval 1.3 to 12.6
|
SECONDARY outcome
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)Population: 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. Here "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.
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. 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.
Outcome measures
| Measure |
Lorlatinib
n=13 Participants
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.
|
|---|---|
|
IC-TTR as Per INV as Assessed by RECIST v 1.1
|
2.8 Months
Interval 1.3 to 15.3
|
SECONDARY outcome
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)Population: Safety analysis set included all enrolled participants who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Lorlatinib
n=71 Participants
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.
|
|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
|
69 Participants
Interval 1.3 to 15.3
|
SECONDARY outcome
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)Population: Safety analysis set included all enrolled participants who took at least 1 dose of study intervention.
An 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. An AE was considered treatment related if investigator considered event related to study drugs or the information was unknown.
Outcome measures
| Measure |
Lorlatinib
n=71 Participants
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.
|
|---|---|
|
Number of Participants With Treatment-Related TEAEs
|
64 Participants
Interval 1.3 to 15.3
|
SECONDARY outcome
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)Population: Safety analysis set included all enrolled participants who took at least 1 dose of study intervention.
An 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, 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.
Outcome measures
| Measure |
Lorlatinib
n=71 Participants
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.
|
|---|---|
|
Number of Participants With Maximum Grade 3 or 4 TEAEs by National Cancer Institute Common Terminology Criteria for AEs [NCI CTCAE] v.4.03
|
28 Participants
Interval 1.3 to 15.3
|
SECONDARY outcome
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)Population: Safety analysis set included all enrolled participants who took at least 1 dose of study intervention.
An 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. 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.
Outcome measures
| Measure |
Lorlatinib
n=71 Participants
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.
|
|---|---|
|
Number of Participants With Maximum Grade 3 or 4 Treatment-Related AEs
|
19 Participants
Interval 1.3 to 15.3
|
SECONDARY outcome
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)Population: Safety analysis set included all enrolled participants who took at least 1 dose of study intervention.
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).
Outcome measures
| Measure |
Lorlatinib
n=71 Participants
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.
|
|---|---|
|
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)
|
23 Participants
Interval 1.3 to 15.3
|
SECONDARY outcome
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)Population: Safety analysis set included all enrolled participants who took at least 1 dose of study intervention.
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/ 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.
Outcome measures
| Measure |
Lorlatinib
n=71 Participants
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.
|
|---|---|
|
Number of Participants With Treatment-Related TESAEs
|
1 Participants
Interval 1.3 to 15.3
|
Adverse Events
Lorlatinib 100mg
Serious adverse events
| Measure |
Lorlatinib 100mg
n=71 participants at risk
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.
|
|---|---|
|
Cardiac disorders
Right ventricular dysfunction
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Gastrointestinal disorders
Dysphagia
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
General disorders
Disease progression
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
General disorders
General physical health deterioration
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Infections and infestations
COVID-19
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Infections and infestations
COVID-19 pneumonia
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Infections and infestations
Infectious pleural effusion
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Infections and infestations
Pneumonia
|
2.8%
2/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Infections and infestations
Pneumonia viral
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Nervous system disorders
Cerebrovascular accident
|
2.8%
2/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Nervous system disorders
Cranial nerve disorder
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Nervous system disorders
Guillain-Barre syndrome
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Nervous system disorders
Intracranial pressure increased
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Nervous system disorders
Syncope
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Renal and urinary disorders
Acute kidney injury
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Renal and urinary disorders
Hydronephrosis
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial haemorrhage
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.2%
3/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
4.2%
3/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.4%
1/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
Other adverse events
| Measure |
Lorlatinib 100mg
n=71 participants at risk
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.
|
|---|---|
|
General disorders
Asthenia
|
19.7%
14/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
General disorders
Fatigue
|
7.0%
5/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
General disorders
Oedema
|
8.5%
6/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
General disorders
Oedema peripheral
|
36.6%
26/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
General disorders
Pyrexia
|
16.9%
12/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Infections and infestations
COVID-19
|
11.3%
8/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Investigations
Alanine aminotransferase increased
|
5.6%
4/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Investigations
Blood cholesterol increased
|
26.8%
19/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Investigations
Blood creatinine increased
|
7.0%
5/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Investigations
Blood glucose increased
|
5.6%
4/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Investigations
Blood triglycerides increased
|
22.5%
16/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Investigations
SARS-CoV-2 test positive
|
7.0%
5/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Investigations
Weight increased
|
9.9%
7/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
33.8%
24/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
16.9%
12/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
38.0%
27/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
5.6%
4/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.7%
9/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.6%
4/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.7%
9/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Nervous system disorders
Dizziness
|
5.6%
4/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Nervous system disorders
Headache
|
7.0%
5/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Nervous system disorders
Paraesthesia
|
9.9%
7/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.3%
8/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.9%
12/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
5.6%
4/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.5%
6/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Vascular disorders
Hypertension
|
5.6%
4/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Blood and lymphatic system disorders
Anaemia
|
16.9%
12/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Gastrointestinal disorders
Diarrhoea
|
18.3%
13/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Gastrointestinal disorders
Nausea
|
8.5%
6/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
|
Gastrointestinal disorders
Vomiting
|
8.5%
6/71 • 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)
Safety analysis set. Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. All-cause mortality: number of deaths are reported from Day 1 of the study up to 28-35 days post last dose and deaths which occurred after 28-35 days post last dose of study drug are also included.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER