CompletedNCT01449461Updated Aug 17, 2021Results posted

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumor Activity of the Oral Anaplastic Lymphoma Kinase (ALK)/Epidermal Growth Factor Receptor (EGFR) Inhibitor Brigatinib (AP26113)

A Phase 1/2 interventional study of Brigatinib in Lymphoma, Large-Cell, Anaplastic and Carcinoma, Non-Small-Cell Lung, sponsored by Ariad Pharmaceuticals. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-08-17.

Sponsored by Ariad Pharmaceuticals · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 137
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

The purpose of this study is 2-fold: initially, in the dose escalation phase, the goal is to determine the safety profile of orally administered brigatinib, including: the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), recommended phase 2 dose (RP2D), and pharmacokinetic (PK) profile. Then, once the RP2D is established, an expansion phase will assess the preliminary anti-tumor activity of brigatinib, both in non-small cell lung cancer (NSCLC) with ALK gene rearrangement (including participants with active brain metastases) or mutated EGFR, and in other cancers with abnormal targets against which brigatinib is active.

Read the detailed description

The drug being tested in this study is called brigatinib (AP26113). Brigatinib is being tested to treat people with NSCLC. This study will look at the safety, tolerability and efficacy of brigatinib.

The study enrolled 137 patients. Participants were assigned to one of the following treatment groups:

Brigatinib 30 mg once daily (QD)/60 mg QD
Brigatinib 90 mg QD
Brigatinib 120 mg QD/60 mg twice daily (BID)
Brigatinib 90 mg QD-180 mg QD
Brigatinib 180 mg QD/90 mg BID
Brigatinib 240 mg QD/120 mg BID/300 mg QD

This multi-center trial will be conducted worldwide. The overall expected time to participate in this study is approximately 4 years. Participants will make multiple visits to the clinic, and 30 days after the End-of-Treatment visit. Follow-up is intended to continue for at least 2 years after the initial dose.

Conditions studied

Lymphoma, Large-Cell, Anaplastic
Carcinoma, Non-Small-Cell Lung

Browse trials for

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 137 is above the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

Ariad Pharmaceuticals is the lead sponsor of 13 studies on the registry; none are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 5 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

General Eligibility Criteria

All participants must have tumor tissue available for analysis. If sufficient tissue is not available, participants must undergo a biopsy to obtain adequate samples. For participants in expansion cohorts 2, 3 and 5, for whom failure of prior therapy is specified (crizotinib for cohorts 2 and 5, one epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for cohort 3), tumor tissue must be available following failure of the prior therapy.
Must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST).
Male or female participants ≥ 18 years old.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Minimum life expectancy of 3 months or more.
Adequate renal and hepatic function.
Adequate bone marrow function.
Normal QT interval on screening electrocardiogram (ECG) evaluation.
For females of childbearing potential, a negative pregnancy test must be documented prior to enrollment.
Female participants who are of childbearing potential and fertile male participants must agree to use an effective form of contraception with their sexual partners throughout study participation.
Signed and dated informed consent indicating that the participant has been informed of all pertinent aspects of the study.
Willingness and ability to comply with scheduled visits and study procedures.

Cohort-specific Eligibility Criteria

PART 1: Dose Escalation Phase:

Histologically confirmed advanced malignancies. All histologies except leukemia;
Refractory to available therapies or for whom no standard or available curative treatments exist;
Tumor tissue available for analysis.

PART 2: Expansion cohorts (5 additional cohorts):

Expansion cohort 1: Non-small cell lung cancer (NSCLC) participants whose tumors exhibit anaplastic lymphoma kinase (ALK) rearrangements and who have not been treated with previous ALK inhibitors.

i. Histologically or cytologically confirmed NSCLC; ii. Tumor tissue available for analysis (see General Eligibility Criterion 1; iii. History of ALK rearrangement by fluorescence in situ hybridization (FISH); iv. No prior ALK inhibitor therapy; 2. Expansion cohort 2: NSCLC participants whose tumors exhibit ALK rearrangements and who are resistant to crizotinib: i. Histologically or cytologically confirmed NSCLC; ii. Tumor tissue available for analysis (see General Eligibility Criterion 1); iii. History of ALK rearrangement by FISH; iv. Resistant to crizotinib (and have not received any other prior ALK inhibitor therapy); 3. Expansion cohort 3: NSCLC participants whose tumors exhibit an epidermal growth factor receptor EGFR-T790M mutation and who are resistant to 1 prior EGFR TKI: i. Histologically or cytologically confirmed NSCLC ii. Previous treatment with only 1 EGFR TKI for which the last administration was within 30 days of the initiation of brigatinib; iii. Documented evidence of an EGFR-T790M mutation following disease progression on the most recent EGFR TKI therapy; iv. No intervening systemic therapy between cessation of the EGFR TKI and initiating brigatinib; v. Tumor tissue available for analysis (see General Eligibility Criterion 1). 4. Expansion cohort 4: Participants with any cancers with abnormalities in ALK or other brigatinib targets. Examples include, but are not limited to, anaplastic large cell lymphoma (ALCL), diffuse large-cell lymphoma (DLCL), inflammatory myofibroblastic tumors (IMT), and other cancers with ALK abnormalities, or tumors with ROS1 fusions: i. Histologically confirmed lymphomas and other cancers, with the exception of leukemias; ii. Tumor tissue available for analysis (see General Eligibility Criterion 1). 5. Expansion Cohort 5: NSCLC participants whose tumors exhibit ALK rearrangements and who have active, measurable brain metastases: i. Histologically or cytologically confirmed NSCLC: ii. Tumor tissue available for analysis (see General Eligibility Criterion 1); iii. History of ALK rearrangement by FISH; iv. Either crizotinib naive or resistant; v. Have at least one measurable brain lesion (≥ 10 mm by contrast enhanced, T1 weighted magnetic resonance imaging [cMRI]). Previously treated brain lesions by stereotactic radiosurgery (SRS) or surgical resection should not be included as a target or non-target lesion; vi. Previously untreated brain metastases with radiologically documented new or progressing brain lesions. Unequivocal progression of previously treated lesions (non-SRS and non-surgically treated lesions) at least 3 months after the last treatment; vii. Neurologically stable. Participants must be on a stable or deceasing dose of corticosteroids and/or have no requirement for anticonvulsants for 5 days prior to the baseline MRI and for 5 days prior to initiating brigatinib.

Exclusion criteria

Exclusion Criteria:

Received an investigational agent ≤ 14 days prior to initiating brigatinib.
Received systemic anticancer therapy (including monoclonal antibodies and irreversible TKIs such as afatinib or dacomitinib) or radiation therapy ≤ 14 days prior to initiating brigatinib.
a. Except for a reversible TKI (ie, erlotinib or gefitinib) or crizotinib, which are allowed up to 72 hours prior to initiating brigatinib, provided that the participant is free of treatment-related toxicity that might confound the safety evaluation of brigatinib.
Received any prior agents targeted against ALK, with the exception of crizotinib, or received more than 1 prior EGFR TKI.
a. Re-challenge with the same TKI is allowed.
Major surgery within 28 days prior to initiating brigatinib.
Brain metastases that are neurologically unstable or require anticonvulsants or an increasing dose of corticosteroids.
1. Participants with previously treated brain metastases without evidence of disease or recurrence are allowed for cohorts 1-4.
2. Participants with evaluable but non-measurable, active brain lesions who otherwise meet the criteria for cohort 5 for CNS disease can be enrolled in other cohorts.
Significant uncontrolled or active cardiovascular disease.
Uncontrolled hypertension (diastolic blood pressure [BP] > 100 mm Hg; systolic > 150 mm Hg).
Prolonged QT interval, or being treated with medications known to cause Torsades de Pointes.
History or presence of pulmonary interstitial disease or drug-related pneumonitis.
Ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection.
Known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history.
Pregnant or breastfeeding.
Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of brigatinib.
Any condition or illness that, in the opinion of the Investigator, would compromise participant safety or interfere with the evaluation of the safety of the drug.
Leptomeningeal carcinomatosis and spinal cord compression. In the case of suspected meningeal involvement, a negative lumbar puncture prior to study entry is required.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 137 participants (actual)

Study arms

Experimental
Brigatinib 30 mg QD/60 mg QD
Brigatinib 30 mg/60 mg, tablets, orally, once daily (QD) in each cycle of 28 days (Approximately up to 7.3 years).
Drug: Brigatinib
Experimental
Brigatinib 90 mg QD
Brigatinib 90 mg, tablets, orally, QD in each cycle of 28 days (Approximately up to 7.3 years).
Drug: Brigatinib
Experimental
Brigatinib 120 mg QD/60 mg BID
Brigatinib 120 mg, once daily or 60 mg, twice daily (BID), tablets, orally, in each cycle of 28 days (Approximately up to 7.3 years).
Drug: Brigatinib
Experimental
Brigatinib 90 mg QD-180 mg QD
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in cycle 2 and onward cycles of 28 days.
Drug: Brigatinib
Experimental
Brigatinib 180 mg QD/90 mg BID
Brigatinib 180 mg, once daily or 90 mg, BID, tablets, orally in each cycle of 28 days (Approximately up to 7.3 years).
Drug: Brigatinib
Experimental
Brigatinib 240 mg QD/120 mg BID/300 mg QD
Brigatinib 240 mg, QD or 120 mg, BID or 300 mg once daily, tablets, orally, in each cycle of 28 days (Approximately up to 7.3 years).
Drug: Brigatinib

Interventions

DrugBrigatinib
Brigatinib tablets and capsules.
Also known as: ALUNBRIG™, AP26113

What researchers measure

Primary outcomes

Recommended Phase 2 Dose (RP2D) of Brigatinib
The RP2D is the maximum tolerated dose (MTD) or less. The MTD is defined as the dose range at which ≤ 1 of 6 evaluable participants experience dose limiting toxicities (DLT) within the first 28 days of treatment (end of Cycle 1).
Time frame: 28 days
Objective Response Rate (ORR)
ORR assessed by the investigator, is defined as the percentage of the participants with complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid tumors (RECIST) v1.1 after the initiation of study treatment. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis. CR for non-target lesion: Disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (\<10mm short axis) and normalization of tumor marker level. PR: at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters. Crzb=Crizotinib.
Time frame: From Screening and at 8-week intervals thereafter up to end of the study (up to 8.4 years)

Secondary outcomes

Number of Participants Who Had at Least One Treatment-Emergent Adverse Event (TEAE)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: From first dose of study drug up to 30 days following the last dose of the study treatment or the investigator/participant decision to discontinue treatment, whichever occurs first (approximately up to 7.4 years)
Maximum Tolerated Dose (MTD) Assessed in Dose Escalation Phase of the Study
The MTD is defined as the highest dose at which ≤ 1 of 6 evaluable participants experience a DLT within the first 28 days of treatment (end of Cycle 1).
Time frame: Up to Cycle 1 (28 days)
Number of Participants With Dose Limiting Toxicities (DLTs) Assessed in Dose Escalation Phase of the Study
DLT include any toxicity that is possibly, probably, or definitely drug-related. Toxicity grades will be defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. DLTs are defined by the following: A) Non-hematologic toxicities: Any grade ≥3 non-hematologic toxicity, with the exception of self-limiting or medically controllable toxicities (eg, nausea, vomiting, fatigue, electrolyte disturbances, hypersensitivity reactions) lasting \< 3 days, and excluding alopecia. B) Hematologic toxicities: Febrile neutropenia not related to underlying disease (fever, \> 101°F; ANC\<500); Prolonged grade 4 neutropenia (\> 7 days); Neutropenic infection: ≥ grade 3 neutropenia with ≥ grade 3 infection; Thrombocytopenia ≥ grade 3 with bleeding or grade 4 lasting ≥ 7 days. C) Missed ≥ 25% of planned doses of brigatinib over 28 days due to treatment-related AEs in the first cycle.
Time frame: Up to Cycle 1 (28 days)
Cmax: Maximum Observed Plasma Concentration for Brigatinib at Cycle 1 Day 1
Time frame: Cycle 1 (28-days cycle): Day 1
Cmax: Maximum Observed Plasma Concentration for Brigatinib at Cycle 2 Day 1
Time frame: Cycle 2 (28-days cycle): Day 1
Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Brigatinib at Cycle 1 Day 1
Time frame: Cycle 1 (28-days cycle): Day 1
Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Brigatinib at Cycle 2 Day 1
Time frame: Cycle 2 (28-days cycle): Day 1
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Brigatinib at Cycle 1 Day 1
Time frame: Cycle 1 (28-days cycle): Day 1 multiple time points (up to 24 hours) post-dose
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Brigatinib at Cycle 2 Day 1
Time frame: Cycle 2 (28-days cycle): Day 1 multiple time points (up to 24 hours) post-dose
T1/2: Terminal Phase Elimination Half-life for Brigatinib at Cycle 2 Day 1
Time frame: Cycle 2 (28-days cycle): Day 1
Best Overall Response
Best overall response is defined as percentage of participants with CR, PR, stable disease (SD) or progressive disease (PD) as per of RECIST v1.1 as evaluated by investigator. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis. CR for non-target lesion: disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (\<10mm short axis) and normalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. Disease progression for target lesion: SLD increased by at least 20% from smallest value on study and SLD must also demonstrate an absolute increase of at least 5 mm or development of any new lesion. PD for non-target lesion: unequivocal progression of existing non-target lesions. SD for neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Screening and at 8-week intervals thereafter up to end of the study (up to 8.4 years)
Duration of Response
Duration of response is defined as time interval from time that measurement criteria are first met for CR/PR (whichever is first recorded) until first date that progressive disease is objectively documented or death due to any cause. Participants who did not progress nor die were censored at last valid response assessment.CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis.CR for non-target lesion:disappearance of all extranodal non-target lesions,all lymph nodes must be non-pathological in size(\<10mm short axis) and normalization of tumor marker level.PR:at least a 30% decrease in SLD of target lesions.PD for target lesion:SLD increased by at least 20% from smallest value and must also demonstrate an absolute increase of \>=5 mm or development of any new lesion.PD for non-target lesion:unequivocal progression of existing non-target lesions.Duration of response calculated by Kaplan-Meier estimation.
Time frame: Screening and at 8-week intervals thereafter up to end of the study (up to 8.4 years)
Progression Free Survival (PFS)
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. Disease progression for target lesion: SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest) and SLD must also demonstrate an absolute increase of at least 5 mm or development of any new lesion. Disease progression for non-target lesion: Unequivocal progression of existing non-target lesions. (Subjective judgment by experienced reader).
Time frame: Screening and at 8-week intervals thereafter up to end of the study (up to 8.4 years)
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.
Time frame: Screening and at 8-week intervals thereafter up to end of the study (up to 8.4 years)
Intracranial Objective Response Rate
Intracranial objective response rate is defined as the percentage of the participants with CR or PR in the intracranial CNS per modification of RECIST v1.1 after the initiation of study drug. CR for target lesion: disappearance of all extranodal lesions. CR for non-target lesion: disappearance of all extranodal non-target lesions and normalization of tumor marker level. PR: at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters.
Time frame: Screening and at 8-week intervals thereafter (approximately up to 50 months)
Duration of Intracranial Response
Intracranial duration of response is defined as the time interval from the time that the measurement criteria are first met for CR/PR in brain metastases (whichever is first recorded) until the first date that progressive disease is objectively documented or death due to any cause. Participants who did not progress nor die were censored at the last valid response assessment. Duration intracranial of response was calculated by Kaplan-Meier estimation.
Time frame: Screening and at 8-week intervals thereafter (approximately up to 50 months)
Intracranial Progression Free Survival (PFS)
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 in brain, or death due to any cause, whichever occurs first. Intracranial PFS was calculated by Kaplan-Meier estimation.
Time frame: Screening and at 8-week intervals thereafter (approximately up to 50 months)

Results

Posted Jun 21, 2017

Participant flow

Participants took part in the study at 9 investigative sites in the United States and Spain from 20 September 2011 to 18 February 2020.

Participant flow — Overall Study
Milestone	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD
Started	6	18	18	32	48	15
Completed	0	0	0	0	0	0
Not completed	6	18	18	32	48	15
Withdrew: Adverse event	0	3	2	3	4	4
Withdrew: Death	0	2	0	0	7	1
Withdrew: Physician decision	0	1	0	4	1	0
Withdrew: Documented progressive disease	4	7	14	15	24	5
Withdrew: Clinical progressive disease	2	2	0	3	4	2
Withdrew: Protocol violation	0	0	0	1	0	0
Withdrew: Site terminated by sponsor	0	1	2	3	4	1
Withdrew: Withdrawal by subject	0	1	0	0	2	1
Withdrew: Reason not specified	0	1	0	3	2	1

Outcome measures

PrimaryRecommended Phase 2 Dose (RP2D) of Brigatinib

The RP2D is the maximum tolerated dose (MTD) or less. The MTD is defined as the dose range at which ≤ 1 of 6 evaluable participants experience dose limiting toxicities (DLT) within the first 28 days of treatment (end of Cycle 1).

Time frame:: 28 days
Reported as:: Mean · mg

Recommended Phase 2 Dose (RP2D) of Brigatinib
mg	Brigatinib
Recommended Phase 2 Dose (RP2D) of Brigatinib	NA (90 to 180)

PrimaryObjective Response Rate (ORR)

ORR assessed by the investigator, is defined as the percentage of the participants with complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid tumors (RECIST) v1.1 after the initiation of study treatment. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis. CR for non-target lesion: Disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (\<10mm short axis) and normalization of tumor marker level. PR: at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters. Crzb=Crizotinib.

Time frame:: From Screening and at 8-week intervals thereafter up to end of the study (up to 8.4 years)
Reported as:: Number · percentage of participants

Objective Response Rate (ORR)
percentage of participants	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD
With Prior Treatment with Crizotinib	0 (0 to 0)	53.8 (25.1 to 80.8)	60.0 (14.7 to 94.7)	76.0 (54.9 to 90.6)	65.2 (42.7 to 83.6)	25.0 (0.6 to 80.6)
Without Prior Treatment with Crizotinib	—	100.0 (2.5 to 100.0)	100.0 (2.5 to 100.0)	100.0 (29.2 to 100.0)	100.0 (15.8 to 100.0)	100.0 (2.5 to 100.0)

SecondaryNumber of Participants Who Had at Least One Treatment-Emergent Adverse Event (TEAE)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Time frame:: From first dose of study drug up to 30 days following the last dose of the study treatment or the investigator/participant decision to discontinue treatment, whichever occurs first (approximately up to 7.4 years)
Reported as:: Count of participants · Participants

Number of Participants Who Had at Least One Treatment-Emergent Adverse Event (TEAE)
Participants	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD
Number of Participants Who Had at Least One Treatment-Emergent Adverse Event (TEAE)	6	18	18	32	48	15

SecondaryMaximum Tolerated Dose (MTD) Assessed in Dose Escalation Phase of the Study

The MTD is defined as the highest dose at which ≤ 1 of 6 evaluable participants experience a DLT within the first 28 days of treatment (end of Cycle 1).

Time frame:: Up to Cycle 1 (28 days)
Reported as:: Number · mg

Maximum Tolerated Dose (MTD) Assessed in Dose Escalation Phase of the Study
mg	Brigatinib
Maximum Tolerated Dose (MTD) Assessed in Dose Escalation Phase of the Study	NA

SecondaryNumber of Participants With Dose Limiting Toxicities (DLTs) Assessed in Dose Escalation Phase of the Study

DLT include any toxicity that is possibly, probably, or definitely drug-related. Toxicity grades will be defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. DLTs are defined by the following: A) Non-hematologic toxicities: Any grade ≥3 non-hematologic toxicity, with the exception of self-limiting or medically controllable toxicities (eg, nausea, vomiting, fatigue, electrolyte disturbances, hypersensitivity reactions) lasting \< 3 days, and excluding alopecia. B) Hematologic toxicities: Febrile neutropenia not related to underlying disease (fever, \> 101°F; ANC\<500); Prolonged grade 4 neutropenia (\> 7 days); Neutropenic infection: ≥ grade 3 neutropenia with ≥ grade 3 infection; Thrombocytopenia ≥ grade 3 with bleeding or grade 4 lasting ≥ 7 days. C) Missed ≥ 25% of planned doses of brigatinib over 28 days due to treatment-related AEs in the first cycle.

Time frame:: Up to Cycle 1 (28 days)
Reported as:: Number · participants

Number of Participants With Dose Limiting Toxicities (DLTs) Assessed in Dose Escalation Phase of the Study
participants	Brigatinib 30 mg	Brigatinib 60 mg	Brigatinib 90 mg	Brigatinib 120 mg	Brigatinib 180 mg	Brigatinib 240 mg	Brigatinib 300 mg
Number of Participants With Dose Limiting Toxicities (DLTs) Assessed in Dose Escalation Phase of the Study	0	0	0	0	0	1	1

SecondaryCmax: Maximum Observed Plasma Concentration for Brigatinib at Cycle 1 Day 1

Time frame:: Cycle 1 (28-days cycle): Day 1
Reported as:: Mean · ng/mL

Cmax: Maximum Observed Plasma Concentration for Brigatinib at Cycle 1 Day 1
ng/mL	Brigatinib 30 mg	Brigatinib 60 mg	Brigatinib 90 mg	Brigatinib 120 mg	Brigatinib 180 mg	Brigatinib 240 mg	Brigatinib 300 mg
Cmax: Maximum Observed Plasma Concentration for Brigatinib at Cycle 1 Day 1	125.6 ± 41.07	406.3 ± 102	493 ± 289.5	793.7 ± 828.7	1185 ± 607.6	1515 ± 637.9	895 ± 487.9

SecondaryCmax: Maximum Observed Plasma Concentration for Brigatinib at Cycle 2 Day 1

Time frame:: Cycle 2 (28-days cycle): Day 1
Reported as:: Mean · ng/mL

Cmax: Maximum Observed Plasma Concentration for Brigatinib at Cycle 2 Day 1
ng/mL	Brigatinib 30 mg	Brigatinib 60 mg	Brigatinib 90 mg	Brigatinib 120 mg	Brigatinib 180 mg	Brigatinib 240 mg	Brigatinib 300 mg
Cmax: Maximum Observed Plasma Concentration for Brigatinib at Cycle 2 Day 1	249.50 ± 167.58	491.67 ± 223.95	634.07 ± 310.05	942.30 ± 472.33	1694.3 ± 1014.3	2280.0 ± 1308.5	—

SecondaryTmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Brigatinib at Cycle 1 Day 1

Time frame:: Cycle 1 (28-days cycle): Day 1
Reported as:: Median · hours

Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Brigatinib at Cycle 1 Day 1
hours	Brigatinib 30 mg	Brigatinib 60 mg	Brigatinib 90 mg	Brigatinib 120 mg	Brigatinib 180 mg	Brigatinib 240 mg	Brigatinib 300 mg
Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Brigatinib at Cycle 1 Day 1	3.9 (3.8 to 4.0)	1.0 (0.48 to 4.0)	2.0 (0.48 to 24)	2.0 (0.98 to 6.0)	2.0 (0.60 to 25)	2.0 (1.0 to 4.0)	4.05 (4 to 4.1)

SecondaryTmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Brigatinib at Cycle 2 Day 1

Time frame:: Cycle 2 (28-days cycle): Day 1
Reported as:: Median · hours

Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Brigatinib at Cycle 2 Day 1
hours	Brigatinib 30 mg	Brigatinib 60 mg	Brigatinib 90 mg	Brigatinib 120 mg	Brigatinib 180 mg	Brigatinib 240 mg	Brigatinib 300 mg
Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Brigatinib at Cycle 2 Day 1	2.49 (0.98 to 4.0)	1.00 (0.50 to 1.8)	2.00 (0.98 to 8.0)	3.00 (0.50 to 6.1)	2.10 (0.50 to 6.2)	2.00 (1.0 to 4.0)	—

SecondaryAUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Brigatinib at Cycle 1 Day 1

Time frame:: Cycle 1 (28-days cycle): Day 1 multiple time points (up to 24 hours) post-dose
Reported as:: Mean · h*ng/mL

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Brigatinib at Cycle 1 Day 1
h*ng/mL	Brigatinib 30 mg	Brigatinib 60 mg	Brigatinib 90 mg	Brigatinib 120 mg	Brigatinib 180 mg	Brigatinib 240 mg	Brigatinib 300 mg
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Brigatinib at Cycle 1 Day 1	1320.9 ± 576.29	3900 ± 430.31	5710.1 ± 3268.4	9895.5 ± 11772	13204 ± 6306.9	16800 ± 7571.1	12356 ± 5869

SecondaryAUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Brigatinib at Cycle 2 Day 1

Time frame:: Cycle 2 (28-days cycle): Day 1 multiple time points (up to 24 hours) post-dose
Reported as:: Mean · h*ng/mL

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Brigatinib at Cycle 2 Day 1
h*ng/mL	Brigatinib 30 mg	Brigatinib 60 mg	Brigatinib 90 mg	Brigatinib 120 mg	Brigatinib 180 mg	Brigatinib 240 mg	Brigatinib 300 mg
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Brigatinib at Cycle 2 Day 1	2689.0 ± 1145.5	5069.0 ± 1664.7	9142.1 ± 4076.7	13888 ± 7011.4	23478 ± 14463	30117 ± 19921	—

SecondaryT1/2: Terminal Phase Elimination Half-life for Brigatinib at Cycle 2 Day 1

Time frame:: Cycle 2 (28-days cycle): Day 1
Reported as:: Mean · hours

T1/2: Terminal Phase Elimination Half-life for Brigatinib at Cycle 2 Day 1
hours	Brigatinib 30 mg	Brigatinib 60 mg	Brigatinib 90 mg	Brigatinib 120 mg	Brigatinib 180 mg	Brigatinib 240 mg	Brigatinib 300 mg
T1/2: Terminal Phase Elimination Half-life for Brigatinib at Cycle 2 Day 1	31.55 ± 2.758	30.93 ± 5.873	28.69 ± 10.06	25.52 ± 7.958	24.90 ± 7.437	21.77 ± 4.007	—

SecondaryBest Overall Response

Best overall response is defined as percentage of participants with CR, PR, stable disease (SD) or progressive disease (PD) as per of RECIST v1.1 as evaluated by investigator. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis. CR for non-target lesion: disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (\<10mm short axis) and normalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. Disease progression for target lesion: SLD increased by at least 20% from smallest value on study and SLD must also demonstrate an absolute increase of at least 5 mm or development of any new lesion. PD for non-target lesion: unequivocal progression of existing non-target lesions. SD for neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Time frame:: Screening and at 8-week intervals thereafter up to end of the study (up to 8.4 years)
Reported as:: Number · percentage of participants

Best Overall Response
percentage of participants	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD
With Prior Treatment with Crizotinib: Complete Response	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	12.0 (2.5 to 31.2)	8.7 (1.1 to 28.0)	0.0 (0.0 to 0.0)
Without Prior Treatment with Crizotinib: Complete Response	—	0.0 (0.0 to 0.0)	100.0 (2.5 to 100.0)	33.3 (0.8 to 90.6)	0.0 (0.0 to 0.0)	100.0 (2.5 to 100.0)
With Prior Treatment with Crizotinib: Partial Response	0.0 (0.0 to 0.0)	53.8 (25.1 to 80.8)	60.0 (14.7 to 94.7)	64.0 (42.5 to 82.0)	56.5 (34.5 to 76.8)	25.0 (0.6 to 80.6)
Without Prior Treatment with Crizotinib: Partial Response	—	100.0 (2.5 to 100.0)	0.0 (0.0 to 0.0)	66.7 (9.4 to 99.2)	100.0 (15.8 to 100.0)	0.0 (0.0 to 0.0)
With Prior Treatment with Crizotinib: Stable Disease	100.0 (2.5 to 100.0)	23.1 (5.0 to 53.8)	0.0 (0.0 to 0.0)	12.0 (2.5 to 31.2)	13.0 (2.8 to 33.6)	75.0 (19.4 to 99.4)
Without Prior Treatment with Crizotinib: Stable Disease	—	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)
With Prior Treatment with Crizotinib: Progressive Disease	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	8.0 (1.0 to 26.0)	21.7 (7.5 to 43.7)	0.0 (0.0 to 0.0)
Without Prior Treatment with Crizotinib: Progressive Disease	—	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)

SecondaryDuration of Response

Duration of response is defined as time interval from time that measurement criteria are first met for CR/PR (whichever is first recorded) until first date that progressive disease is objectively documented or death due to any cause. Participants who did not progress nor die were censored at last valid response assessment.CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis.CR for non-target lesion:disappearance of all extranodal non-target lesions,all lymph nodes must be non-pathological in size(\<10mm short axis) and normalization of tumor marker level.PR:at least a 30% decrease in SLD of target lesions.PD for target lesion:SLD increased by at least 20% from smallest value and must also demonstrate an absolute increase of \>=5 mm or development of any new lesion.PD for non-target lesion:unequivocal progression of existing non-target lesions.Duration of response calculated by Kaplan-Meier estimation.

Time frame:: Screening and at 8-week intervals thereafter up to end of the study (up to 8.4 years)
Reported as:: Median · months

Duration of Response
months	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD
With Prior Treatment with Crizotinib	—	11.1 (3.8 to 16.7)	4.0 (3.7 to 29.5)	14.8 (7.9 to 25.1)	20.4 (7.5 to 51.6)	29.7 (NA to NA)
Without Prior Treatment with Crizotinib	—	30.4 (NA to NA)	60.3 (NA to NA)	52.0 (5.6 to 52.0)	20.8 (9.2 to 32.4)	NA (NA to NA)

SecondaryProgression Free Survival (PFS)

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. Disease progression for target lesion: SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest) and SLD must also demonstrate an absolute increase of at least 5 mm or development of any new lesion. Disease progression for non-target lesion: Unequivocal progression of existing non-target lesions. (Subjective judgment by experienced reader).

Time frame:: Screening and at 8-week intervals thereafter up to end of the study (up to 8.4 years)
Reported as:: Median · months

Progression Free Survival (PFS)
months	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD
Progression Free Survival (PFS)	1.8 (1.0 to 5.5)	12.6 (0.9 to 47.9)	5.4 (0.8 to 63.9)	11.0 (0.5 to 53.6)	5.4 (0.1 to 69.9)	5.4 (1.8 to 31.5)

SecondaryOverall 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.

Time frame:: Screening and at 8-week intervals thereafter up to end of the study (up to 8.4 years)
Reported as:: Median · months

Overall Survival (OS)
months	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD
Overall Survival (OS)	5.3 (2.3 to 12.6)	11.6 (4.0 to 47.6)	7.3 (0.5 to 28.6)	17.9 (1.4 to 35.0)	7.3 (0.1 to 55.0)	8.3 (3.3 to 22.3)

SecondaryIntracranial Objective Response Rate

Intracranial objective response rate is defined as the percentage of the participants with CR or PR in the intracranial CNS per modification of RECIST v1.1 after the initiation of study drug. CR for target lesion: disappearance of all extranodal lesions. CR for non-target lesion: disappearance of all extranodal non-target lesions and normalization of tumor marker level. PR: at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters.

Time frame:: Screening and at 8-week intervals thereafter (approximately up to 50 months)
Reported as:: Number · percentage of participants

Intracranial Objective Response Rate
percentage of participants	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD
Measurable Brain Metastases	—	100 (15.8 to 100)	—	80 (28.4 to 99.5)	42.9 (9.9 to 81.6)	100 (2.5 to 100)
Only Non-Measurable Brain Metastases	—	16.7 (0.4 to 64.1)	100 (2.5 to 100)	46.2 (19.2 to 74.9)	44.4 (13.7 to 78.8)	50.0 (1.3 to 98.7)

SecondaryDuration of Intracranial Response

Intracranial duration of response is defined as the time interval from the time that the measurement criteria are first met for CR/PR in brain metastases (whichever is first recorded) until the first date that progressive disease is objectively documented or death due to any cause. Participants who did not progress nor die were censored at the last valid response assessment. Duration intracranial of response was calculated by Kaplan-Meier estimation.

Time frame:: Screening and at 8-week intervals thereafter (approximately up to 50 months)
Reported as:: Median · months

Duration of Intracranial Response
months	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD
Duration of Intracranial Response	—	12.9 (NA to NA)	5.0 (NA to NA)	11.4 (7.5 to 11.4)	29.2 (5.5 to 29.2)	11.3 (3.6 to 18.9)

SecondaryIntracranial Progression Free Survival (PFS)

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 in brain, or death due to any cause, whichever occurs first. Intracranial PFS was calculated by Kaplan-Meier estimation.

Time frame:: Screening and at 8-week intervals thereafter (approximately up to 50 months)
Reported as:: Median · months

Intracranial Progression Free Survival (PFS)
months	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD
Intracranial Progression Free Survival (PFS)	—	36.8 (5.5 to 36.8)	6.7 (NA to NA)	NA (9.4 to NA)	14.4 (7.3 to 31.1)	7.3 (3.1 to 22.3)

Adverse events

Collected over All-Cause Mortality: From first dose up to the End of the Study (Up to 8.4 years). Serious and other adverse events: From first dose of study drug up to 30 days following the last dose of the study treatment or the investigator/participant decision to discontinue treatment, whichever occurs first (approximately up to 7.4 years). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Brigatinib 30 mg QD/60 mg QD	6/6 (100%)	1/6 (16.7%)	6/6 (100%)
Brigatinib 90 mg QD	11/18 (61.1%)	10/18 (55.6%)	17/18 (94.4%)
Brigatinib 120 mg QD/60 mg BID	12/18 (66.7%)	10/18 (55.6%)	17/18 (94.4%)
Brigatinib 90 mg QD-180 mg QD	17/32 (53.1%)	14/32 (43.8%)	31/32 (96.9%)
Brigatinib 180 mg QD/90 mg BID	25/48 (52.1%)	30/48 (62.5%)	45/48 (93.8%)
Brigatinib 240 mg QD/120 mg BID/300 mg QD	11/15 (73.3%)	11/15 (73.3%)	15/15 (100%)

Most frequent serious events

Showing 10 of 103

Most frequent serious events
Event	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD
DyspnoeaRespiratory, thoracic and mediastinal disorders	0/6	0/18	1/18	1/32	2/48	4/15
Neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/6	4/18	1/18	1/32	5/48	0/15
PneumoniaInfections and infestations	0/6	2/18	3/18	1/32	4/48	0/15
Metastases to central nervous systemNeoplasms benign, malignant and unspecified (incl cysts and polyps)	1/6	0/18	0/18	0/32	1/48	0/15
HypoxiaRespiratory, thoracic and mediastinal disorders	0/6	1/18	0/18	1/32	1/48	2/15
CoughRespiratory, thoracic and mediastinal disorders	0/6	0/18	0/18	0/32	0/48	2/15
Pericardial effusion malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/6	0/18	0/18	3/32	1/48	0/15
Pleural effusionRespiratory, thoracic and mediastinal disorders	0/6	0/18	1/18	0/32	1/48	1/15
PneumothoraxRespiratory, thoracic and mediastinal disorders	0/6	0/18	0/18	0/32	0/48	1/15
BronchitisInfections and infestations	0/6	1/18	0/18	0/32	0/48	1/15

Most frequent other events

Showing 10 of 307

Most frequent other events
Event	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD
FatigueGeneral disorders	2/6	9/18	9/18	16/32	19/48	12/15
NauseaGastrointestinal disorders	3/6	8/18	9/18	16/32	33/48	8/15
DiarrhoeaGastrointestinal disorders	1/6	8/18	7/18	17/32	21/48	8/15
CoughRespiratory, thoracic and mediastinal disorders	1/6	7/18	6/18	13/32	14/48	8/15
Abdominal painGastrointestinal disorders	3/6	1/18	2/18	6/32	5/48	2/15
HeadacheNervous system disorders	0/6	8/18	7/18	14/32	18/48	6/15
VomitingGastrointestinal disorders	1/6	1/18	5/18	9/32	19/48	5/15
Aspartate aminotransferase increasedInvestigations	0/6	3/18	7/18	10/32	9/48	2/15
Upper respiratory tract infectionInfections and infestations	1/6	0/18	3/18	12/32	7/48	3/15
Lipase increasedInvestigations	0/6	5/18	4/18	12/32	6/48	3/15

Baseline characteristics

Safety population included all enrolled participants who received at least one dose of study drug.

Age, Continuous
Age, Continuous(years)	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD	Total
Mean	66.8 ± 9.30	57.9 ± 12.93	57.8 ± 10.91	55.7 ± 11.41	53.9 ± 11.10	58.5 ± 15.60	56.4 ± 12.02

Age, Customized
Age, Customized(Participants)	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD	Total
Adults [18-64 years]	2	11	12	25	39	9	98
From 65 to 84 years	4	7	6	7	9	6	39

Sex: Female, Male
Sex: Female, Male(Participants)	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD	Total
Female	3	12	13	14	29	8	79
Male	3	6	5	18	19	7	58

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD	Total
American Indian or Alaska Native	0	0	0	1	1	0	2
Asian	0	4	3	3	5	2	17
Black or African American	0	1	2	0	1	1	5
Native Hawaiian or Other Pacific Islander	0	0	0	0	1	0	1
White	6	13	13	27	39	12	110
Unknown	0	0	0	0	1	0	1
Other	0	0	0	1	0	0	1

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD	Total
Hispanic or Latino	1	0	0	1	1	0	3
Not Hispanic or Latino	5	18	18	31	47	15	134

Region of Enrollment
Region of Enrollment(Participants)	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD	Total
United States	6	18	18	32	41	15	130
Spain	0	0	0	0	7	0	7

Eastern Cooperative Oncology Group (ECOG) Performance Score
Eastern Cooperative Oncology Group (ECOG) Performance Score(Participants)	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD	Total
0	0	3	3	13	13	2	34
1	6	15	15	19	33	13	101
2	0	0	0	0	2	0	2

Time Since Diagnosis of Cancer
Time Since Diagnosis of Cancer(years)	Brigatinib 30 mg QD/60 mg QD	Brigatinib 90 mg QD	Brigatinib 120 mg QD/60 mg BID	Brigatinib 90 mg QD-180 mg QD	Brigatinib 180 mg QD/90 mg BID	Brigatinib 240 mg QD/120 mg BID/300 mg QD	Total
Mean	2.48 ± 3.303	3.33 ± 2.184	2.41 ± 1.346	3.19 ± 2.726	2.77 ± 2.053	3.27 ± 1.913	2.93 ± 2.192

4 further baseline measures are reported on the registry.

Study locations

No study locations are listed for this record.

References and documents

Publications

Camidge DR, Kim DW, Tiseo M, Langer CJ, Ahn MJ, Shaw AT, Huber RM, Hochmair MJ, Lee DH, Bazhenova LA, Gold KA, Ou SI, West HL, Reichmann W, Haney J, Clackson T, Kerstein D, Gettinger SN. Exploratory Analysis of Brigatinib Activity in Patients With Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer and Brain Metastases in Two Clinical Trials. J Clin Oncol. 2018 Sep 10;36(26):2693-2701. doi: 10.1200/JCO.2017.77.5841. Epub 2018 May 16. PubMed 29768119 ↗
Gettinger SN, Bazhenova LA, Langer CJ, Salgia R, Gold KA, Rosell R, Shaw AT, Weiss GJ, Tugnait M, Narasimhan NI, Dorer DJ, Kerstein D, Rivera VM, Clackson T, Haluska FG, Camidge DR. Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial. Lancet Oncol. 2016 Dec;17(12):1683-1696. doi: 10.1016/S1470-2045(16)30392-8. Epub 2016 Nov 8. PubMed 27836716 ↗
Yu HA, Riely GJ. Second-generation epidermal growth factor receptor tyrosine kinase inhibitors in lung cancers. J Natl Compr Canc Netw. 2013 Feb 1;11(2):161-9. doi: 10.6004/jnccn.2013.0024. PubMed 23411383 ↗

Study documents

Study protocol · Mar 20, 2017
Statistical analysis plan · Apr 14, 2016

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting information: Study protocol, Sap, Icf, Csr

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 17, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01449461
Lead sponsor: Ariad Pharmaceuticals
Responsible party: Sponsor
First posted: Oct 10, 2011
Start date: Sep 20, 2011
Primary completion: Nov 16, 2015
Completion: Feb 18, 2020
Results posted: Jun 21, 2017
Last update: Aug 17, 2021

Study contacts

Medical Director

study director · Takeda

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2021. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Lymphoma→

Other studies from this sponsor

Ariad Pharmaceuticals

Start the discussion