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ALK-positive Advanced NSCLCPhase 2NCT03410108

Phase 2 Study of Brigatinib in Japanese Participants With Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer (NSCLC)

A Phase 2 study testing Brigatinib in people with ALK-positive Advanced NSCLC, run by Takeda at 33 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate efficacy and safety of brigatinib in Japanese participants with anaplastic lymphoma kinase (ALK)-positive NSCLC. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
ALK-positive Advanced NSCLC
What is being tested?
Brigatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
104 participants
Where
33 sitesJapan
Study dates
29 Jan 2018to 28 Jul 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female Japanese participants aged >=20 years on the day of consent.
  • Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
  • Have histologically or cytologically confirmed stage IIIB, stage IIIC (locally advanced or recurrent and not a candidate for definitive multimodality therapy), or stage IV NSCLC.
  • Have documentation of ALK rearrangement that meets following criteria.
  • For the Safety Evaluation Lead-in Part and the Refractory Expansion Part, participants must meet 1 of the following 2 criteria:
  • Have documentation of ALK rearrangement by a positive result from the Vysis ALK Break Apart fluorescence in situ hybridization (FISH) Probe Kit, the Nichirei Histofine ALK iAEP Kit, or the Ventana ALK (D5F3) Companion Diagnostics (CDx) Assay at any time during prior disease course. The sponsor may require an adequate tissue available for central laboratory testing by the Vysis ALK Break Apart FISH test if a documented ALK rearrangement is confirmed by a positive result from the Nichirei Histofine ALK iAEP Kit "ONLY".
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  • Had a documented ALK rearrangement by a different test at any time during prior disease course, and adequate tissue available for central laboratory testing by the Vysis ALK Break Apart FISH test. Central confirmation of ALK rearrangement is not required before enrollment.
  • For TKI-naïve Expansion Cohort, participants must meet the following criteria Have documentation of ALK rearrangement by a positive result from Ministry of Health, Labour and Welfare (MHLW) Approved tests (e.g Vysis ALK Break Apart FISH Probe Kit, the Nichirei Histofine ALK iAEP Kit, or the Ventana ALK [D5F3] CDx Assay) prior to enrollment, and required to submit sufficient tumor tissue for central laboratory testing upon request of sponsor. Central confirmation of ALK rearrangement is not required before enrollment
  • The Refractory Expansion Part only: had documented progressive disease (PD) during treatment or within 30 days after discontinuation of treatment with ALK inhibitor.
  • Note 1: The Refractory Expansion Part consists of the Main Cohort and a Sub-cohort based on prior ALK inhibitor treatment. The Main Cohort includes participants who had previously received alectinib (as their only ALK inhibitor) or both crizotinib and alectinib (regardless the sequence of those 2 ALK inhibitors), and a total of 47 participants will be enrolled. Participants with all other sequences of up to 2 prior ALK inhibitor(s) may be included in the Sub-cohort, and the number of participants will be limited to 20.
  • Note 2: Participants who will be included in the Main Cohort of the refractory should have documented PD during treatment or within 30 days after discontinuation of treatment with alectinib.
  • Have at least 1 measurable (ie, target) lesion per RECIST version 1.1. Note: Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy. Brain lesions may not be used as target lesions if they were 1) previously treated with whole brain radiation therapy (WBRT) within 3 months, or 2) previously treated by stereotactic radiosurgery (SRS) or surgical resection.
  • 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 is allowed.
  • Have a life expectancy of >=3 months.
  • Have adequate organ and hematologic function, as determined by:
  • Both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =<2.5 times the upper limit of the normal range (ULN) (=<5×ULN is acceptable if liver metastases are present).
  • Total serum bilirubin =<1.5×ULN (<3.0×ULN for participants with Gilbert syndrome).
  • Serum creatinine <1.5×ULN. For participants with creatinine levels above or equal to 1.5×ULN, the participant is eligible if the estimated creatinine clearance using the Cockcroft-Gault formula is >=30 mL/minute.
  • Serum lipase =<1.5×ULN and serum amylase =<1.5×ULN.
  • Absolute neutrophil count (ANC) >=1.5×10^9/Liter (L).
  • Platelet count >=75×10^9/L.
  • Hemoglobin >=9 gram (g)/ deciliter (dL).
  • Percutaneous oxygen saturation (SpO2) >=94% without oxygen support. Participants who need oxygen support are excluded.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of =<2.
  • Must meet the following criteria:
  • Female participants who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to practice 1 highly effective non-hormonal method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant, from the time of signing the informed consent through 4 months after that last dose of study drug. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
  • Male participants, even if surgically sterilized (ie, status postvasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant, during the entire study treatment period and through 4 months after that last dose of study drug. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
  • Have the willingness and ability to comply with scheduled visit and study procedures.

Who cannot join

  • Previously received the following treatments. The Refractory Expansion Part only: received any prior ALK inhibitor not specified in the protocol.
  • TKI-naïve Expansion Cohort only: received any prior TKI including but not limited to ALK inhibitor and vascular endothelial growth factor receptor (VEGFR) TKI.
  • The Refractory Expansion Part only: received more than 2 prior ALK inhibitors. Note: The Safety Evaluation Lead-in Part allows participants with any line of prior ALK inhibitor which includes treatment-naïve participants; however, ALK inhibitor-naïve participants may be enrolled after the confirmation of first 3 dose-limiting toxicity (DLT) evaluable participants to have no more than 1 DLT during Cycle 1 by investigator's judgement.
  • The Safety Evaluation Lead-in Part and the Refractory Expansion Part only: received ALK inhibitor within 7 days before the first dose of brigatinib.
  • Previously received more than 1 regimen (more than 3 regimens in the Safety Evaluation Lead-in part) of systemic anticancer therapy (other than ALK inhibitors) for locally advanced or metastatic disease. Note: A systemic anticancer therapy regimen will be counted if it is administered over at least 1 cycle. A new anticancer agent used as maintenance therapy will be counted as a new regimen unless it was previously used as initial anticancer therapy. Neoadjuvant or adjuvant systemic anticancer therapy will be counted as a prior regimen if completion of (neo) adjuvant therapy occurred <12 months before the first dose of brigatinib.
  • Treatment with any investigational products within 30 days or 5 half-lives of that investigational agent, whichever is longer, before the first dose of brigatinib.
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  • Received chemotherapy or radiation within 14 days before the first dose of brigatinib, except stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.
  • Received antineoplastic monoclonal antibodies within 30 days before the first dose of brigatinib.
  • Received systemic treatment with strong inhibitors or strong and moderate inducers of cytochrome P450 (CYP) 3A within 7 days before the first dose of brigatinib.
  • Had major surgery within 30 days before the first dose of brigatinib. Minor surgical procedures such as venous catheter placement or minimally invasive biopsies are allowed.
  • Have been diagnosed with another primary malignancy other than NSCLC, except for the following adequately/definitively treated malignancies: nonmelanoma skin cancer, cervical cancer in situ, nonmetastatic prostate cancer; or participant with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
  • Have symptomatic central nervous system (CNS) metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within 7 days before the first dose of brigatinib. Note: If a participant has worsening neurological symptoms or signs due to CNS metastasis, the participant needs to complete local therapy and be neurologically stable (with no requirement for an increasing dose of corticosteroids or use of anticonvulsants for symptomatic control) for 7 days before the first dose of brigatinib.
  • Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with asymptomatic leptomeningeal disease and without cord compression are allowed.
  • Have ongoing or history of interstitial lung disease (ILD) (including interstitial pneumonitis, pneumonitis, radiation pneumonitis, drug-related pneumonitis, organized pneumonia, and pulmonary alveolitis).
  • Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not limited to:
  • Myocardial infarction within 6 months before the first dose of brigatinib.
  • Unstable angina within 6 months before the first dose of brigatinib.
  • Congestive heart failure within 6 months before the first dose of brigatinib.
  • Uncontrolled atrial arrhythmias despite appropriate medical therapy.
  • History of ventricular arrhythmia, including history of ventricular tachycardia, ventricular fibrillation, or torsades de pointes. Participants with premature ventricular contractions are allowed.
  • Cerebrovascular accident or transient ischemic attack within 6 months before the first dose of brigatinib.
  • Have uncontrolled hypertension. Participants with hypertension should be under treatment at the start of screening and demonstrate adequate control of blood pressure.
  • Have an ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics.
  • Have a known history of human immunodeficiency virus (HIV) infection. Testing is not required in the absence of history.
  • Hepatitis B surface antigen (HBsAg) positive, detectable hepatitis B viral load, or detectable hepatitis C virus (HCV) infection viral load. Note: Participants who have positive hepatitis B core antibody (HBcAb) or hepatitis B surface antibody (HBsAb) can be enrolled but must have an undetectable hepatitis B viral load. Participants who have positive HCV antibody can be enrolled but must have an undetectable hepatitis C viral load.
  • Have malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of brigatinib.
  • Have a known or suspected hypersensitivity to brigatinib or its excipients.
  • Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period. Note: Female participants who are lactating will be excluded, even if they discontinue breastfeeding.
  • Have any condition or illness that, in the opinion of the investigator, would compromise participant safety or interfere with the evaluation of brigatinib.

Trial locations and contacts

33 sites in 1 country.

33 sites in 1 country

Japan33 sites

  • Hyogo Cancer Center

    Akashi, Hyōgo

  • Juntendo University Hospital

    Bunkyo-ku, Tokyo

  • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

    Bunkyo-ku, Tokyo

  • Chiba University Hospital

    Chiba

  • National Cancer Center Hospital

    Chuo-ku, Tokyo

  • Kyushu University Hospital

    Fukuoka

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka

  • Kansai Medical University Hospital

    Hirakata, Osaka

  • Kanazawa University Hospital

    Kanazawa, Ishikawa-ken

  • National Cancer Center Hospital East

    Kashiwa, Chiba

  • Kobe City Medical Center General Hospital

    Kobe, Hyōgo

  • Cancer Institute Hospital

    Koto-ku, Tokyo

  • Kurashiki Central Hospital

    Kurashiki, Okayama-ken

  • Kurume University Hospital

    Kurume, Fukuoka

  • Kyoto University Hospital

    Kyoto

  • National Hospital Organization Shikoku Cancer Center

    Matsuyama, Ehime

  • Matsuzaka Citizen's Hospital

    Matsuzaka, Mie-ken

  • Iwate Medical University Hospital

    Morioka, Iwate

  • Shizuoka Cancer Center

    Nagaizumi-cho, Shizuoka

  • Aichi Cancer Center Hospital

    Nagoya, Aichi-ken

  • Nagoya University Hospital

    Nagoya, Aichi-ken

  • Niigata Cancer Center Hospital

    Niigata

  • Okayama University Hospital

    Okayama

  • Osaka City General Hospital

    Osaka

  • Osaka International Cancer Institute

    Osaka

  • Hokkaido Cancer Center

    Sapporo, Hokkaido

  • Kindai University Hospital

    Sayama, Osaka

  • Sendai Kousei Hospital

    Sendai, Miyagi

  • Jichi Medical University Hospital

    Shimotsuke, Tochigi

  • Saitama Cancer Center

    Shinden, Saitama

  • Fujita Health University Hospital

    Toyoake, Aichi-ken

  • Wakayama Medical University Hospital

    Wakayama

  • Kanagawa Cancer Center

    Yokohama, Kanagawa

Other trials in Japan

About this study

Official title: A Single-Arm, Multicenter, Phase 2 Study of Brigatinib in Japanese Patients With ALK-Positive Non-Small Cell Lung Cancer (NSCLC)

The purpose of this study is to evaluate efficacy and safety of brigatinib in Japanese participants with anaplastic lymphoma kinase (ALK)-positive NSCLC.

Read the detailed description

The drug being tested in this study is called brigatinib. Brigatinib is being tested in participants with ALK-positive NSCLC in order to evaluate efficacy and safety of oral doses of brigatinib in Japanese participants with ALK-positive NSCLC.

The study will enroll approximately 110 participants. Participants will be enrolled in non-randomized and opened manner:

  • Brigatinib 90 mg for the first 7 days, followed by Brigatinib 180 mg of Brigatinib tablets, once daily in a 28-days cycle.

All participants will be asked to take tablets of brigatinib once daily with or without food throughout the study.

This multi-center trial will be conducted in Japan. The overall time to participate in this study is approximately 53 months. Participants will make multiple visits to the clinic during the treatment period, and posttreatment period including a follow-up assessment after last dose of study drug.

Being tested
Brigatinib
Keywords
Drug therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BrigatinibDrug

    Brigatinib tablet

Study groups in NCT03410108
Study groupRoleWhat they receive
Brigatinib 90 mg + Brigatinib 180 mgExperimentalBrigatinib 90 milligram (mg), tablets, orally, once daily (QD) for first 7 days followed by brigatinib, 180 mg, tablets, orally, QD in Cycle 1 of 28 days followed by brigatinib 180 mg, tablets, orally, QD in Cycle 2 and onward cycles of 28 days until investigator-assessed progressive disease (PD) or intolerable toxicity, withdrawal of consent, or discontinuation for any other reason, whichever comes first up to Cycle 34 of 28-day cycle, until data cut-off date 29 September 2020.
Receives: Drug: Brigatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Confirmed Objective Response Rate (ORR) in the Main Cohort of the Refractory Expansion Part

    Confirmed ORR: Percentage of participants confirmed to have achieved complete response(CR) or partial response(PR) per Independent Review Committee(IRC) using Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1 after the initiation of study treatment(confirmed ≥4 weeks after initial response). CR(target lesion response): disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to <10 mm in short axis. CR(non-target lesion response): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size(<10 mm short axis) and normalization of tumor marker level. PR(target lesions): at least 30% decrease in sum of the longest diameters(SLD) of target lesions, taking as reference Baseline sum diameters. As pre-specified in the protocol, this outcome measure was assessed and reported data only in the participants with at least 1 line of prior treatment(called as Main Cohort) of the Refractory Expansion Part.

    Measured: From the start of study treatment up to confirmed CR or PR (Up to approximately 23 months)

  2. 12 Months Progression-Free Survival (PFS) Rate in the Tyrosine Kinase Inhibitor (TKI) Naïve Expansion Cohort

    12 months PFS rate was defined as the percentage of the participants who did not have PFS events (PD per IRC using RECIST version 1.1, or death by any cause) at 12 months after the start of study treatment. PD for target lesion: SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm. PD for non-target lesion: unequivocal progression of existing nontarget lesions. Kaplan-Meier method was used for analysis of percentage of participants who achieved PFS of 12 months. As pre-specified in the protocol, this outcome measure was assessed and reported data only in the TKI-Naïve Expansion Cohort (participants with no prior treatment).

    Measured: From the start of study treatment up to Month 12

Secondary outcomes (19)

  1. Confirmed ORR as Assessed by an IRC in All Refractory Participants and TKI-Naïve Expansion Cohort

    Confirmed ORR was defined as percentage of participants who were confirmed to have achieved CR or PR per an IRC using RECIST version 1.1 after initiation of study treatment (confirmed ≥4 weeks after initial response). CR for target lesion response: disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to <10 mm in short axis. CR for non-target lesion response: disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (<10 mm short axis) and normalization of tumor marker level. PR: at least a 30% decrease in SLD of target lesions, taking as reference baseline sum diameters. As pre-specified in the protocol, the data for this outcome measure is reported based on previous treatment as: All Refractory Participants, and TKI-Naive Expansion Cohort.

    Measured: From the start of study treatment up to confirmed CR or PR till data cut-off date: 29 September 2020 (Up to approximately 32 months)

  2. Confirmed ORR as Assessed by the Investigator in Main Cohort of the Refractory Expansion Part, Safety Evaluation Lead-in Part, and TKI-Naive Expansion Cohort

    Confirmed ORR was defined as the percentage of the participants who were confirmed to have achieved CR or PR per the investigator using RECIST version 1.1 after the initiation of study treatment (confirmed ≥4 weeks after initial response). CR for target lesion response: disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to <10 mm in short axis. CR for non-target lesion response: disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (<10 mm 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. As pre-specified in the protocol, this outcome measure assessed and reports data per cohort: Main Cohort of the Refractory Expansion Part and TKI-Naive Expansion Cohort. The Safety Evaluation Lead-in Part was excluded from the analysis.

    Measured: From the start of study treatment up to confirmed CR or PR till data cut-off date: 29 September 2020 (Up to approximately 32 months)

  3. Duration of Response (DOR) as Assessed by an IRC in the Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort

    DOR was assessed by an IRC, per RECIST version 1.1. DOR was defined as the time between the first documentation of objective tumor response (CR or PR) and the first subsequent documentation of objective PD or death due to any cause, whichever occurs first. PD for target lesion: SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm. PD for non-target lesion: unequivocal progression of existing nontarget lesions. Only responders were analyzed for this outcome measure. As pre-specified in the protocol, this outcome measure assessed and reports data per cohort: Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort.

    Measured: From first dose at 8-week intervals through Cycle 15 (each cycle=28 days) and at 12-week intervals thereafter until disease progression or death, whichever occurs first till data cut-off date: 29 September 2020 (Up to approximately 32 months)

  4. Progression-Free Survival (PFS) as Assessed by an IRC in the Main Cohort of the Refractory Expansion Part, and All Refractory Participants

    PFS was assessed by an IRC, per RECIST version 1.1. PFS was defined as the time from the start of study treatment to the first documentation of objective PD or to death due to any cause, whichever occurs first. PD for target lesion: SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm. PD for non-target lesion: unequivocal progression of existing nontarget lesions. This outcome measure reports the data in refractory participants only and data is reported per cohort separately for Main Cohort of the Refractory Expansion Part, and for All Refractory Participants.

    Measured: From the start of the treatment up to disease progression or death due to any cause, whichever comes first till data cut-off date: 29 September 2020 (Up to approximately 32 months)

  5. PFS as Assessed by an IRC in the TKI-Naive Expansion Cohort

    PFS was assessed by an IRC, per RECIST version 1.1. PFS was defined as the time from the start of study treatment to the first documentation of objective PD or to death due to any cause, whichever occurs first. PD for target lesion: SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm. PD for non-target lesion: unequivocal progression of existing nontarget lesions. This outcome measure reports data only in the TKI-Naive Expansion Cohort.

    Measured: From the start of the treatment up to disease progression or death due to any cause, whichever comes first till data cut-off date: 29 September 2020 (Up to approximately 32 months)

  6. Disease Control Rate (DCR) as Assessed by an IRC in the Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort

    DCR was assessed by an IRC, per RECIST version 1.1. DCR: percentage of participants confirmed to have achieved CR or PR or have best overall response of stable disease (SD), for 6 weeks or more after initiation of study drug. CR (target lesion): disappearance of all target lesions. CR (non-target lesions): the nontarget lesion(s) has fully resolved. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. SD (target lesion): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD (target lesion): SLD increased by at least 20% from the smallest value on study, the SLD must also demonstrate an absolute increase of at least 5 mm. As pre-specified in the protocol, this outcome measure assessed and reports data per cohort: Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort.

    Measured: From the start of the treatment up to confirmed CR or PR or SD till data cut-off date: 29 September 2020 (Up to approximately 32 months)

  7. Time to Response as Assessed by an IRC in the Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort

    Time to response was assessed by an IRC, per RECIST version 1.1. and was defined as the time interval from the date of the first dose of study treatment until the initial observation of CR or PR for participants with confirmed CR/PR. CR(target lesion response):disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to <10 mm in short axis. CR(non-target lesion response):disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (<10 mm 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. As pre-specified in the protocol, this outcome measure assessed and reports data per cohort: Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort.

    Measured: From the start of the treatment up to confirmed CR or PR till data cut-off date: 29 September 2020 (Up to approximately 32 months)

  8. Overall Survival (OS) as Assessed by an IRC in the Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort

    OS is defined as the time interval from the date of the first dose of the study treatment until death due to any cause. As pre-specified in the protocol, this outcome measure assessed and reports data per cohort: Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort.

    Measured: From the start of the treatment up to death due to any cause till data cut-off date: 29 September 2020 (Up to approximately 32 months)

  9. Intracranial Objective Response Rate (iORR) in Participants With Measurable Central Nervous System (CNS) Metastases at Baseline in the Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort

    Confirmed iORR was defined as the percentage of the participants who had achieved confirmed CR or PR in the intracranial CNS per modified RECIST version 1.1 as evaluated by an IRC after the initiation of study treatment. CR for target lesion: disappearance of all target lesions. CR for non-target lesions: the nontarget lesion(s) has fully resolved. PR for target lesion: at least a 30% decrease in SLD of target lesions, taking as reference the Baseline SLD. Additionally, progression of target lesions must not be present. As pre-specified in the protocol, this outcome measure assessed and reports data per cohort: Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort.

    Measured: From the start of the treatment up to confirmed CR or PR till data cut-off date: 29 September 2020 (Up to approximately 32 months)

  10. Duration of Intracranial Response (iDOR) in Participants With Measurable CNS Metastases at Baseline in the Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-naive Expansion Cohort

    iDOR was assessed by an IRC, per modified RECIST version 1.1 and was defined as the time between first documentation of objective intracranial tumor response (CR or PR) and first subsequent documentation of objective intracranial PD or death due to any cause. Participants who had systemic PD without intracranial PD were censored. CR (target lesion): disappearance of all target lesions. CR (non-target lesions):the nontarget lesion(s) has fully resolved. PR (target lesion):at least a 30% decrease in SLD of target lesions, taking as reference Baseline SLD. Progression of target lesions must not be present. CNS PD (target lesions):at least a 20% increase in SLD of target lesions, taking as reference the nadir SLD (or the baseline) and SLD must also demonstrate an absolute increase of ≥5 mm. As pre-specified in the protocol, this outcome measure assessed and reports data per cohort: Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort.

    Measured: From first dose at 8-week intervals through Cycle 15 (each cycle=28 days) and at 12-week intervals thereafter until intracranial disease progression or death due to any cause till data cut-off date: 29 September 2020 (Up to approximately 32 months)

  11. Intracranial Progression-free Survival (iPFS) in the Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort

    iPFS was assessed by an IRC, per modified RECIST version 1.1 and was defined as the time from the start of study treatment to the first documentation of objective intracranial PD or death due to any cause, whichever occurred first. The participant who had systemic PD and withdrawn from study without intracranial PD was censored. CNS PD for target lesions: at least a 20% increase in the SLD of target lesions, taking as reference the nadir SLD (or the baseline, if the baseline is the nadir value) and the SLD must also demonstrate an absolute increase of ≥5 mm. PD for non-target lesions: the nontarget site of disease has shown unequivocal progression. As pre-specified in the protocol, this outcome measure was assessed and reports data per cohort in all participants with measurable or not measurable intracranial metastases at Baseline: Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort.

    Measured: From the start of the treatment up to intracranial disease progression or death due to any cause, whichever comes first till data cut-off date: 29 September 2020 (Up to approximately 32 months)

  12. Time on Treatment in the Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort

    Time on treatment was defined as the time interval from the first dose to the last dose of brigatinib. As pre-specified in the protocol, this outcome measure assessed and reports data per cohort: Main Cohort of the Refractory Expansion Part, All Refractory Participants, and TKI-Naive Expansion Cohort.

    Measured: From the first dose up to last dose of study drug till data cut-off date: 29 September 2020 (Up to approximately 32 months)

  13. Change From Baseline in Patient-Reported Outcomes (PROs) of Health-Related Quality of Life (HRQOL) Scores and Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQC30) Subscale Score

    EORTC QLQ-C30 contains 30 items - 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a QOL scale. Out of 30, 28 questions had 4 response levels (not at all, a little, quite a bit, and very much); 2 questions for global health status had score of 1 to 7 (very poor to excellent) to evaluate overall health and QOL. Each subscale raw score including global health status was transformed to a total score of 0 to 100. For functional scales, global health status scale, higher scores=better QOL (positive change from Baseline=improvement). For symptom scales, lower scores=better QOL (negative change from Baseline=improvement). As pre-specified in protocol, this outcome measure was assessed and reports data per cohort: Refractory Expansion Participants (including Main Cohort and Sub-Cohort), and TKI-Naive Expansion Cohort.

    Measured: Refractory Expansion Participants: Baseline and Cycle 22 - each cycle was of 28 days; TKI-Naive Participants: Baseline and Cycle 19 - each cycle was of 28 days

  14. Change From Baseline in HRQOL Scores and Symptoms of Lung Cancer as Assessed With the EORTC QLQ- Lung Cancer (LC) 13 (QLQ-LC13) Subscale Score

    HRQOL scores was assessed with EORTC, its lung cancer module QLQ-LC13. QLQ-LC13 contains 13 questions (4-point scale where 1=Not at all [best] to 4=Very much [worst]) assessing lung cancer-associated symptoms [cough, hemoptysis, dyspnea, and site-specific pain (chest, arm or shoulder, other parts)], treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Subscale score range: 0 to 100. Higher symptom score = greater degree of symptom severity. As pre-specified in the protocol, this outcome measure assessed and reports data per cohort only in the Refractory Expansion Participants (including Main Cohort and Sub-cohort), and TKI-Naive Expansion Cohort.

    Measured: Refractory Expansion Participants: Baseline and Cycle 22 - each cycle was of 28 days; TKI-Naive Participants: Baseline and Cycle 19 - each cycle was of 28 days

  15. Number of Participants With Responses to HRQOL Scores and Symptoms of Lung Cancer as Assessed With the EuroQol 5-Dimensional Questionnaire (EQ-5D-5L) Score

    EQ-5D-5L comprises of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, 5= extremely severe problems. Higher scores indicated greater levels of problems across the five dimensions. As pre-specified in the protocol, this outcome measure assessed and reports data per cohort only in the Refractory Expansion Participants (including Main Cohort and Sub-cohort), and TKI-Naive Expansion Cohort. Number of participants with a particular score at the given timepoint is reported. Only categories with data are reported.

    Measured: Refractory Expansion Participants: Cycle 22 - each cycle was of 28 days; TKI-Naive Participants: Cycle 19 - each cycle was of 28 days

  16. Change From Baseline in HRQOL Scores and Symptoms of Lung Cancer as Assessed With the EuroQol Visual Analogue Scale (EQ VAS) Score

    The EQ VAS records the respondent's self-rated health on a 20 centimeter (cm), vertical, visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). As pre-specified in the protocol, this outcome measure assessed and reports data per cohort only in the Refractory Expansion Participants (including Main Cohort and Sub-cohort), and TKI-Naive Expansion Cohort.

    Measured: Refractory Expansion Participants: Baseline and Cycle 22 - each cycle was of 28 days; TKI-Naive Participants: Baseline and Cycle 19 - each cycle was of 28 days

  17. Cmax: Maximum Observed Plasma Concentration for Brigatinib on Cycle 1 Days 1 and 22

    As pre-specified in the protocol, this outcome measure was assessed only in the participants with or without prior ALK-TKI treatment called as the Safety Evaluation Lead-in Part.

    Measured: Pre-dose and at multiple time points (0.5, 1, 2, 4, 6, 8, 12, 24; up to 24 hrs) post-dose of Cycle 1 Days 1 and 22 (each cycle = 28 days)

  18. Tmax: Time of First Occurrence of Cmax for Brigatinib on Cycle 1 Days 1 and 22

    As pre-specified in the protocol, this outcome measure was assessed only in the participants with or without prior ALK-TKI treatment called as the Safety Evaluation Lead-in Part.

    Measured: Pre-dose and at multiple time points (0.5, 1, 2, 4, 6, 8, 12, 24; up to 24 hrs) post-dose of Cycle 1 Days 1 and 22 (each cycle = 28 days)

  19. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Brigatinib on Cycle 1 Days 1 and 22

    As pre-specified in the protocol, this outcome measure was assessed only in the participants with or without prior ALK-TKI treatment called as the Safety Evaluation Lead-in Part.

    Measured: Pre-dose and at multiple time points (0.5, 1, 2, 4, 6, 8, 12, 24; up to 24 hrs) post-dose of Cycle 1 Days 1 and 22 (each cycle = 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2018
  2. Study start29 Jan 2018
  3. Primary completion29 Sep 2020
  4. Study completion28 Jul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
104 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03410108
Sponsor's protocol ID
Brigatinib-2001
Other IDs
U1111-1204-8752, JapicCTI-183823
Status last verified
Jun 2022
First submitted
11 Jan 2018
Last updated
8 May 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
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.

Publications

  • Mok T, Nishio M, Yoshida T, Ahn MJ, Kudou K, Asato T, Yang H, Tong X, Vincent S, Zhang P, Yamamoto N, Kim ES. Efficacy and safety of brigatinib after alectinib in patients with ALK-positive NSCLC: Integrated analysis of the ALTA-2 and J-ALTA studies. Lung Cancer. 2025 Nov;209:108793. doi: 10.1016/j.lungcan.2025.108793. Epub 2025 Oct 9.

    PubMed 41110382

  • Sugawara S, Kondo M, Yokoyama T, Kumagai T, Nishio M, Goto K, Nakagawa K, Seto T, Yamamoto N, Kudou K, Asato T, Zhang P, Ohe Y. Brigatinib in Japanese patients with tyrosine kinase inhibitor-naive ALK-positive non-small cell lung cancer: first results from the phase 2 J-ALTA study. Int J Clin Oncol. 2022 Dec;27(12):1828-1838. doi: 10.1007/s10147-022-02232-7. Epub 2022 Aug 29.

    PubMed 36036294

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brigatinib in people with ALK-positive Advanced NSCLC, run by Takeda at 33 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Confirmed Objective Response Rate (ORR) in the Main Cohort of the Refractory Expansion Part (time frame: From the start of study treatment up to confirmed CR or PR (Up to approximately 23 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03410108, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.

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