Trial Outcomes & Findings for A Study of Brigatinib in Participants With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib (NCT NCT03535740)

Last Updated: 2025-07-31

Results Overview

Confirmed ORR is defined as the percentage of the participants who are confirmed to have achieved complete response (CR) or partial response (PR), per RECIST version 1.1 (confirmed ≥4 weeks after initial response), after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis and PR: at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions taking as reference the Baseline sum diameters. Percentages were rounded off to the nearest single decimal place.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

103 participants

Primary outcome timeframe

Up to approximately 20 months from the start of enrollment till data cut-off 30 September 2020

Results posted on

2025-07-31

Participant Flow

Participants took part in the study at 54 investigative sites in Canada, United States, Austria, France, Germany, Italy, Netherlands, Spain, Sweden, China, Hong Kong, Japan, Korea, Taiwan, and Australia from 31 January 2019 to 21 August 2024.

Participants with diagnosis of ALK+, advanced NSCLC were enrolled to receive brigatinib 90 milligrams(mg) followed by 180 mg up to disease progression. 102 participants discontinued study up to interim data cut-off date: 20 May 2021. By 20 May 2021, all primary\&secondary study outcome measure were met\&data collection was complete. 1 participant stayed on until study completion as means to provide access to brigatinib.

Participant milestones

Participant milestones
Measure	Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg Participants received brigatinib 90 mg, tablets, orally, once daily (QD) for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.
Overall Study STARTED	103
Overall Study Participants Who Received Escalated Dose of Brigatinib 240 mg	13
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	103

Reasons for withdrawal

Reasons for withdrawal
Measure	Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg Participants received brigatinib 90 mg, tablets, orally, once daily (QD) for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.
Overall Study Death	44
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	13
Overall Study Site terminated by Sponsor	45

Baseline Characteristics

Number analyzed signifies the number of participants with data available for weight.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=103 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.
Age, Continuous	54.7 years STANDARD_DEVIATION 11.94 • n=103 Participants
Sex: Female, Male Female	52 Participants n=103 Participants
Sex: Female, Male Male	51 Participants n=103 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=103 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	92 Participants n=103 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=103 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=103 Participants
Race (NIH/OMB) Asian	49 Participants n=103 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=103 Participants
Race (NIH/OMB) Black or African American	1 Participants n=103 Participants
Race (NIH/OMB) White	44 Participants n=103 Participants
Race (NIH/OMB) More than one race	0 Participants n=103 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=103 Participants
Region of Enrollment Canada	6 Participants n=103 Participants
Region of Enrollment United States	7 Participants n=103 Participants
Region of Enrollment Austria	1 Participants n=103 Participants
Region of Enrollment France	7 Participants n=103 Participants
Region of Enrollment Germany	3 Participants n=103 Participants
Region of Enrollment Italy	16 Participants n=103 Participants
Region of Enrollment Netherlands	2 Participants n=103 Participants
Region of Enrollment Spain	11 Participants n=103 Participants
Region of Enrollment Sweden	2 Participants n=103 Participants
Region of Enrollment China	14 Participants n=103 Participants
Region of Enrollment Hong Kong	6 Participants n=103 Participants
Region of Enrollment Japan	3 Participants n=103 Participants
Region of Enrollment Korea, South	20 Participants n=103 Participants
Region of Enrollment Taiwan, Province Of China	4 Participants n=103 Participants
Region of Enrollment Australia	1 Participants n=103 Participants
Weight	69.23 kilograms (kg) STANDARD_DEVIATION 15.409 • n=102 Participants • Number analyzed signifies the number of participants with data available for weight.
Height	165.86 centimeters (cm) STANDARD_DEVIATION 10.172 • n=100 Participants • Number analyzed signifies the number of participants with data available for height.

PRIMARY outcome

Timeframe: Up to approximately 20 months from the start of enrollment till data cut-off 30 September 2020

Population: Full Analysis Population included all participants who received at least 1 dose of brigatinib.

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=103 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Confirmed Objective Response Rate (ORR) Using RECIST v1.1 as Assessed by the Independent Review Committee (IRC)	26.2 percentage of participants Interval 18.0 to 35.8	—

SECONDARY outcome

Timeframe: Up to approximately 28 months

Population: Full Analysis Population included all participants who received at least 1 dose of brigatinib.

Confirmed ORR is defined as the percentage of the participants who are confirmed to have achieved CR or PR, per RECIST version 1.1 (confirmed ≥4 weeks after initial response), after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis and PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters. Percentages were rounded off to the nearest single decimal place.

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=103 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Confirmed ORR Using RECIST v1.1 as Assessed by the Investigator	26.2 percentage of participants Interval 18.0 to 35.8	—

SECONDARY outcome

Timeframe: Up to approximately 28 months

Population: Full Analysis Population included all participants who received at least 1 dose of brigatinib. Overall number of participants analyzed is the number of participants who were responders.

DOR is defined as the time interval from the time that the measurement criteria are first met for CR or PR until the first date that the progressive disease (PD) is objectively documented, or death. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis. PR: at least a 30% decrease in the SLD of target lesions taking as reference the Baseline sum diameters. PD: SLD increased by at least 20% from the smallest value on study (including Baseline, if that is the smallest). SLD must also demonstrate an absolute increase of at least 5 mm (2 lesions increasing from, for example, 2 mm to 3 mm, does not qualify).

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=27 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Duration of Response (DOR) as Assessed by the IRC and the Investigator IRC-Assessed DOR	6.341 months Interval 5.552 to The upper limit of 95 % confidence interval was not estimable due to insufficient number of events observed among the responding participants.	—
Duration of Response (DOR) as Assessed by the IRC and the Investigator Investigator-Assessed DOR	6.735 months Interval 4.435 to 9.232	—

SECONDARY outcome

Timeframe: Up to approximately 28 Months

Population: Full Analysis Population included all participants who received at least 1 dose of brigatinib.

PFS is defined as the time interval from the date of the first dose of the study treatment until the first date at which disease progression is objectively documented, or death due to any cause, whichever occurs first. PFS was censored for participants without documented disease progression or death.

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=103 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Progression-Free Survival (PFS) as Assessed by the IRC and the Investigator IRC-Assessed PFS	3.811 months Interval 3.515 to 5.848	—
Progression-Free Survival (PFS) as Assessed by the IRC and the Investigator Investigator-Assessed PFS	3.811 months Interval 3.154 to 5.552	—

SECONDARY outcome

Timeframe: Up to approximately 28 months

Population: Full Analysis Population included all participants who received at least 1 dose of brigatinib.

DCR is defined as the percentage of participants who have achieved CR, PR or stable disease (SD) (in the case of SD, measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks) after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis. PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages were rounded off to the nearest single decimal place.

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=103 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Disease Control Rate (DCR) as Assessed by the IRC and the Investigator IRC-Assessed DCR	54.4 percentage of participants Interval 44.3 to 64.2	—
Disease Control Rate (DCR) as Assessed by the IRC and the Investigator Investigator-Assessed DCR	59.2 percentage of participants Interval 49.1 to 68.8	—

SECONDARY outcome

Timeframe: Up to approximately 28 months

Population: Full Analysis Population included all participants who received at least 1 dose of brigatinib. Overall number of participants analyzed is the number of participants who were responders.

Time to response is defined as the time interval from the date of the first dose of the study treatment until the initial observation of CR or PR. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis. PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=27 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Time to Response as Assessed by the IRC and the Investigator IRC-Assessed Time to Response	1.807 months Interval 1.45 to 5.36	—
Time to Response as Assessed by the IRC and the Investigator Investigator-Assessed Time to Response	1.807 months Interval 1.58 to 10.87	—

SECONDARY outcome

Timeframe: Up to approximately 28 months

Population: Intracranial central nervous system (iCNS) disease population included those participants in the Full Analysis Population who were determined by the IRC to have iCNS metastases at baseline, regardless of whether they had at least 1 lesion that qualified as a target lesion in their baseline assessment by the IRC.

Confirmed iORR is defined as the percentage of the participants who have achieved CR or PR in the brain per a modification of RECIST version 1.1, after the initiation of study treatment, in participants with intracranial brain metastases at baseline. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis. or partial response or PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters. Percentages were rounded off to the nearest single decimal place.

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=55 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Confirmed Intracranial Objective Response Rate (iORR) in Participants With Brain Metastases at Baseline, as Assessed by the IRC	14.5 percentage of participants Interval 6.5 to 26.7	—

SECONDARY outcome

Timeframe: Up to approximately 28 months

Population: iCNS disease population included those participants in the Full Analysis Population who were determined by the IRC to have iCNS metastases at baseline, regardless of whether they had at least 1 lesion that qualified as a target lesion in their baseline assessment by the IRC. Overall number of participants analyzed is the number of participants who were responders.

Duration of intracranial response is defined as the time interval from the time that the measurement criteria are first met for CR or PR until the first date that PD (including baseline, if that is the smallest). SLD must also demonstrate an absolute increase of at least 5 mm. (2 lesions increasing from, for example, 2 mm to 3 mm, does not qualify) in the brain is objectively documented or death, in participants with intracranial metastases at baseline. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis. or partial response or PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters in the brain. PD: SLD increased by at least 20% from the smallest value on study.

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=8 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Duration of Intracranial Response in Participants With Brain Metastases at Baseline, as Assessed by the IRC	NA months Interval 5.717 to The median and upper limit of 95 % confidence interval was not estimable due to insufficient number of events observed among the responding participants.	—

SECONDARY outcome

Timeframe: Up to approximately 28 months

Population: iCNS disease population included of those participants in the Full Analysis Population who were determined by the IRC to have iCNS metastases at baseline, regardless of whether they had at least 1 lesion that qualified as a target lesion in their baseline assessment by the IRC.

iPFS is defined as the time interval from the date of the first dose of the study treatment until the first date at which intracranial brain disease progression is objectively documented, or death due to any cause, whichever occurs first, in participants with intracranial metastases at enrollment. iPFS will be censored for participants without documented intracranial disease progression or death.

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=55 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Intracranial Progression-Free Survival (iPFS) in Participants With Brain Metastases at Baseline, as Assessed by the IRC	5.224 months Interval 3.515 to 7.392	—

SECONDARY outcome

Timeframe: Up to approximately 28 months

Population: Full Analysis Population included all participants who received at least 1 dose of brigatinib.

OS is defined as the time interval from the date of the first dose of the study treatment until death due to any cause. It was censored on the date of last contact for those participants who were alive.

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=103 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Overall Survival (OS)	21.290 months Interval 12.189 to The upper limit of 95 % confidence interval was not estimable due to insufficient number of events observed among the responding participants.	—

SECONDARY outcome

Timeframe: First dose of study drug up to 30 days after last dose (approximately 5 years)

Population: Safety Analysis Population included all participants who received at least 1 dose of brigatinib. As pre-specified in protocol, AEs are reported for 2 sets/arms. Arm 1 (brigatinib 90/180 mg) and Arm 2 (brigatinib 240 mg).

An adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. TEAE: any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=103 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg n=13 Participants Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Number of Participants With One or More Treatment-emergent Adverse Event (TEAE)	103 Participants	12 Participants

SECONDARY outcome

Timeframe: Up to approximately 28 months

Population: Full Analysis Population included all participants who received at least 1 dose of brigatinib. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis for the specified category.

EORTC QLQ-C30 incorporates 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all \[best\] to 4=Very Much \[worst\]) and 2 questions (7-point scale where 1=Very poor \[worst\] to 7= Excellent \[best\]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status scale, higher scores represent better quality of life (QOL); for the symptom scales, lower scores represent better QOL. Improvement is defined as a change from baseline of 10 or more points higher for functional scales and 10 or more points lower for symptom scales.

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=93 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Global Health Status/QoL	52 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Physical Functioning	55 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Role Functioning	53 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Emotional Functioning	36 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Cognitive Functioning	47 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Social Functioning	53 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Fatigue	55 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Nausea and Vomiting	21 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Pain	48 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Dyspnoea Raw	26 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Insomnia	40 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Appetite Loss	30 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Constipation	23 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Diarrhoea	27 Participants	—
Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Financial Difficulties	27 Participants	—

SECONDARY outcome

Timeframe: Up to approximately 28 months

HRQOL scores will be assessed with EORTC, its lung cancer module QLQ-LC13. QLQ-LC13 contains 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Scale score range: 0 to 100. Higher symptom score = greater degree of symptom severity. Improvement is defined as a change from baseline of 10 or more points lower for symptom scales.

Outcome measures

Outcome measures
Measure	Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg n=93 Participants Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.	Brigatinib 240 mg Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator's discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.
Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 Coughing	37 Participants	—
Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 Haemoptysis	4 Participants	—
Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 Sore Mouth	6 Participants	—
Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 Dysphagia	4 Participants	—
Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 Peripheral Neuropathy	25 Participants	—
Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 Alopecia	14 Participants	—
Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 Pain in Chest	24 Participants	—
Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 Pain in Arm or Shoulder	23 Participants	—
Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 Pain in Other Parts	41 Participants	—
Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 Composite Endpoint Score	61 Participants	—
Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 Dyspnoea	45 Participants	—

Adverse Events

Brigatinib 90/180 mg

Serious events: 48 serious events

Other events: 98 other events

Deaths: 39 deaths

Brigatinib 240 mg

Serious events: 3 serious events

Other events: 12 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER