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.

Intent to treat (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.

ITT analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.

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.

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 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.

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.

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.

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.

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 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.

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 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.

Analysis population included all enrolled participants who took at least 1 dose of Lorlatinib and had confirmed CR or PR as per INV.

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.

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 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.

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.

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.

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.

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.

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.

ITT analysis population included all enrolled participants who took at least 1 dose of Lorlatinib.

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.

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 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.

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.

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.

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.

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.

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.

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).

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.

Safety analysis set included all enrolled participants who took at least 1 dose of study intervention.