ALK-positive Advanced NSCLC
Conditions
Keywords
Drug Therapy
Brief summary
The primary purpose of this study is to determine the efficacy of brigatinib by confirmed objective response rate (ORR) by response evaluation criteria in solid tumors (Response Evaluation Criteria in Solid Tumors \[RECIST\]), in participants with ALK+ locally advanced or metastatic NSCLC whose disease has progressed on therapy with alectinib or ceritinib.
Detailed description
The drug being tested in this study is called brigatinib (AP26113). Brigatinib is being tested to treat people who have anaplastic lymphoma kinase-positive (ALK+), advanced non-small-cell lung cancer (NSCLC). The study will enroll approximately 103 patients. Participants will be assigned to the treatment group: • Brigatinib All participants will be asked to take brigatinib 90 mg tablet in lead-in period for 7 days, followed by brigatinib 180 mg at the same time each day throughout the study. Participants with progressive disease had an option to receive an escalated dose of brigatinib 240 mg as per investigator's discretion in case no toxicities (greater than grade 2) are experienced. This multicenter trial will be conducted worldwide. The overall time to participate in this study is approximately 3 years. Participants will make multiple visits to the clinic, and 30 days after last dose of study drug for a follow-up assessment.
Interventions
DRUGBrigatinib
Brigatinib Tablets
Sponsors
Takeda
Ariad Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have histologically or cytologically confirmed stage IIIB (locally advanced or recurrent and not a participant for curative therapy) or stage IV non-small-cell lung cancer (NSCLC). 2. Must meet both of the following 2 criteria: 1. Have documentation of anaplastic lymphoma kinase (ALK) rearrangement by a positive result from any laboratory test® approved by the food and drug administration (FDA) or Have documented ALK rearrangement by a different test (non-FDA-approved local lab tests) and have provided tumor sample to the central laboratory. (Note: Central laboratory ALK rearrangement testing results are not required to be obtained before randomization.) 2. Had been on any one of the ALK tyrosine kinase inhibitor (TKIs) (alectinib, ceritinib, crizotinib) for at least 12 weeks before progression. 3. Had progressive disease (PD) while on alectinib or ceritinib 4. Had alectinib or ceritinib as the most recent ALK inhibitor therapy. 5. Have at least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by the investigator. 6. Had recovered from toxicities related to prior anticancer therapy to national cancer institute common terminology criteria for adverse events (NCI CTCAE), version 4.03, Grade \<=1. (Note: Treatment-related alopecia or peripheral neuropathy that are Grade \>1 are allowed if deemed irreversible.) and have adequate major organ functions. 7. Have a life expectancy of ≥3 months.
Exclusion criteria
1. Had received any prior ALK-targeted TKI other than crizotinib, alectinib, or ceritinib. 2. Had received both alectinib and ceritinib. 3. Had previously received more than 3 regimens of systemic anticancer therapy for locally advanced or metastatic disease. 4. Had symptomatic brain metastasis (parenchymal or leptomeningeal). Participants with asymptomatic brain metastasis or who have stable symptoms that did not require an increased dose of corticosteroids to control symptoms in the past 7 days before the first dose of brigatinib may be enrolled. 5. Had current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed. 6. Had a cerebrovascular accident or transient ischemic attack within 6 months before first dose of brigatinib. 7. Had an ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics. 8. Had malabsorption syndrome or other gastrointestinal (GI) illness that could affect oral absorption of brigatinib.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Objective Response Rate (ORR) Using RECIST v1.1 as Assessed by the Independent Review Committee (IRC) | Up to approximately 20 months from the start of enrollment till data cut-off 30 September 2020 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) as Assessed by the IRC and the Investigator | Up to approximately 28 months | 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). |
| Progression-Free Survival (PFS) as Assessed by the IRC and the Investigator | Up to approximately 28 Months | 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. |
| Disease Control Rate (DCR) as Assessed by the IRC and the Investigator | Up to approximately 28 months | 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. |
| Time to Response as Assessed by the IRC and the Investigator | Up to approximately 28 months | 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. |
| Confirmed Intracranial Objective Response Rate (iORR) in Participants With Brain Metastases at Baseline, as Assessed by the IRC | Up to approximately 28 months | 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. |
| Confirmed ORR Using RECIST v1.1 as Assessed by the Investigator | Up to approximately 28 months | 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. |
| Intracranial Progression-Free Survival (iPFS) in Participants With Brain Metastases at Baseline, as Assessed by the IRC | Up to approximately 28 months | 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. |
| Overall Survival (OS) | Up to approximately 28 months | 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. |
| Number of Participants With One or More Treatment-emergent Adverse Event (TEAE) | First dose of study drug up to 30 days after last dose (approximately 5 years) | 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. |
| 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 | Up to approximately 28 months | 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. |
| Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 | 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. |
| Duration of Intracranial Response in Participants With Brain Metastases at Baseline, as Assessed by the IRC | Up to approximately 28 months | 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. |
Countries
Australia, Austria, Canada, China, France, Germany, Hong Kong, Italy, Japan, Netherlands, South Korea, Spain, Sweden, Taiwan, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg 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. | 103 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 44 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Site terminated by Sponsor | 45 |
| Overall Study | Withdrawal by Subject | 13 |
Baseline characteristics
| Characteristic | Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg |
|---|---|
| Age, Continuous | 54.7 years STANDARD_DEVIATION 11.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 92 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Height | 165.86 centimeters (cm) STANDARD_DEVIATION 10.172 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 49 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) White | 44 Participants |
| Region of Enrollment Australia | 1 Participants |
| Region of Enrollment Austria | 1 Participants |
| Region of Enrollment Canada | 6 Participants |
| Region of Enrollment China | 14 Participants |
| Region of Enrollment France | 7 Participants |
| Region of Enrollment Germany | 3 Participants |
| Region of Enrollment Hong Kong | 6 Participants |
| Region of Enrollment Italy | 16 Participants |
| Region of Enrollment Japan | 3 Participants |
| Region of Enrollment Korea, South | 20 Participants |
| Region of Enrollment Netherlands | 2 Participants |
| Region of Enrollment Spain | 11 Participants |
| Region of Enrollment Sweden | 2 Participants |
| Region of Enrollment Taiwan, Province Of China | 4 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 52 Participants |
| Sex: Female, Male Male | 51 Participants |
| Weight | 69.23 kilograms (kg) STANDARD_DEVIATION 15.409 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 39 / 103 | 5 / 13 |
| other Total, other adverse events | 98 / 103 | 12 / 13 |
| serious Total, serious adverse events | 48 / 103 | 3 / 13 |
Outcome results
Primary
Confirmed Objective Response Rate (ORR) Using RECIST v1.1 as Assessed by the Independent Review Committee (IRC)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Confirmed Objective Response Rate (ORR) Using RECIST v1.1 as Assessed by the Independent Review Committee (IRC) | 26.2 percentage of participants |
p-value: 0.0763Exact Binomial Test
Secondary
Confirmed Intracranial Objective Response Rate (iORR) in Participants With Brain Metastases at Baseline, as Assessed 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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Confirmed Intracranial Objective Response Rate (iORR) in Participants With Brain Metastases at Baseline, as Assessed by the IRC | 14.5 percentage of participants |
Secondary
Confirmed ORR Using RECIST v1.1 as Assessed by the Investigator
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.
Time frame: Up to approximately 28 months
Population: Full Analysis Population included all participants who received at least 1 dose of brigatinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Confirmed ORR Using RECIST v1.1 as Assessed by the Investigator | 26.2 percentage of participants |
Secondary
Disease Control Rate (DCR) as Assessed by the IRC and the Investigator
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.
Time frame: Up to approximately 28 months
Population: Full Analysis Population included all participants who received at least 1 dose of brigatinib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Disease Control Rate (DCR) as Assessed by the IRC and the Investigator | IRC-Assessed DCR | 54.4 percentage of participants |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Disease Control Rate (DCR) as Assessed by the IRC and the Investigator | Investigator-Assessed DCR | 59.2 percentage of participants |
Secondary
Duration of Intracranial Response in Participants With Brain Metastases at Baseline, as Assessed by the IRC
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Duration of Intracranial Response in Participants With Brain Metastases at Baseline, as Assessed by the IRC | NA months |
Secondary
Duration of Response (DOR) as Assessed by the IRC and the Investigator
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Duration of Response (DOR) as Assessed by the IRC and the Investigator | IRC-Assessed DOR | 6.341 months |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Duration of Response (DOR) as Assessed by the IRC and the Investigator | Investigator-Assessed DOR | 6.735 months |
Secondary
Intracranial Progression-Free Survival (iPFS) in Participants With Brain Metastases at Baseline, as Assessed 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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Intracranial Progression-Free Survival (iPFS) in Participants With Brain Metastases at Baseline, as Assessed by the IRC | 5.224 months |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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 |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | 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
Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 | Composite Endpoint Score | 61 Participants |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 | Dyspnoea | 45 Participants |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 | Coughing | 37 Participants |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 | Haemoptysis | 4 Participants |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 | Sore Mouth | 6 Participants |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 | Dysphagia | 4 Participants |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 | Peripheral Neuropathy | 25 Participants |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 | Alopecia | 14 Participants |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 | Pain in Chest | 24 Participants |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 | Pain in Arm or Shoulder | 23 Participants |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13 | Pain in Other Parts | 41 Participants |
Secondary
Number of Participants With One or More Treatment-emergent Adverse Event (TEAE)
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.
Time frame: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Number of Participants With One or More Treatment-emergent Adverse Event (TEAE) | 103 Participants |
| Brigatinib 240 mg | Number of Participants With One or More Treatment-emergent Adverse Event (TEAE) | 12 Participants |
Secondary
Overall Survival (OS)
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.
Time frame: Up to approximately 28 months
Population: Full Analysis Population included all participants who received at least 1 dose of brigatinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Overall Survival (OS) | 21.290 months |
Secondary
Progression-Free Survival (PFS) as Assessed by the IRC and the Investigator
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.
Time frame: Up to approximately 28 Months
Population: Full Analysis Population included all participants who received at least 1 dose of brigatinib.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Progression-Free Survival (PFS) as Assessed by the IRC and the Investigator | IRC-Assessed PFS | 3.811 months |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Progression-Free Survival (PFS) as Assessed by the IRC and the Investigator | Investigator-Assessed PFS | 3.811 months |
Secondary
Time to Response as Assessed by the IRC and the Investigator
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Time to Response as Assessed by the IRC and the Investigator | IRC-Assessed Time to Response | 1.807 months |
| Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg | Time to Response as Assessed by the IRC and the Investigator | Investigator-Assessed Time to Response | 1.807 months |