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

NCT03410108 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: Brigatinib-2001U1111-1204-8752JapicCTI-183823
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 33

Brief Summary

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

Conditions

ALK-positive Advanced NSCLC

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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).

  From the start of study treatment up to Month 12

Secondary Outcomes (19)

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

  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)

• 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

  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)

• 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

  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)

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

  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)

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

  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)

Study Arms (1)

Brigatinib 90 mg + Brigatinib 180 mg

EXPERIMENTAL

Brigatinib 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.

Drug: Brigatinib

Interventions

Brigatinib DRUG

Brigatinib tablet

Brigatinib 90 mg + Brigatinib 180 mg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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".
• 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:

You may not qualify if:

• 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.
• 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:

Sponsors & Collaborators

• Takeda: lead

Study Sites (33)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, Japan

Location

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

Location

Fujita Health University Hospital

Toyoake, Aichi-ken, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Location

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, Japan

Location

Kurume University Hospital

Kurume, Fukuoka, Japan

Location

Hokkaido Cancer Center

Sapporo, Hokkaido, Japan

Location

Hyogo Cancer Center

Akashi, Hyōgo, Japan

Location

Kobe City Medical Center General Hospital

Kobe, Hyōgo, Japan

Location

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, Japan

Location

Iwate Medical University Hospital

Morioka, Iwate, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Location

Matsuzaka Citizen's Hospital

Matsuzaka, Mie-ken, Japan

Location

Sendai Kousei Hospital

Sendai, Miyagi, Japan

Location

Kurashiki Central Hospital

Kurashiki, Okayama-ken, Japan

Location

Kansai Medical University Hospital

Hirakata, Osaka, Japan

Location

Kindai University Hospital

Sayama, Osaka, Japan

Location

Saitama Cancer Center

Shinden, Saitama, Japan

Location

Shizuoka Cancer Center

Nagaizumi-cho, Shizuoka, Japan

Location

Jichi Medical University Hospital

Shimotsuke, Tochigi, Japan

Location

Juntendo University Hospital

Bunkyo-ku, Tokyo, Japan

Location

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

Bunkyo-ku, Tokyo, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Location

Cancer Institute Hospital

Koto-ku, Tokyo, Japan

Location

Chiba University Hospital

Chiba, Japan

Location

Kyushu University Hospital

Fukuoka, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, Japan

Location

Kyoto University Hospital

Kyoto, Japan

Location

Niigata Cancer Center Hospital

Niigata, Japan

Location

Okayama University Hospital

Okayama, Japan

Location

Osaka City General Hospital

Osaka, Japan

Location

Osaka International Cancer Institute

Osaka, Japan

Location

Wakayama Medical University Hospital

Wakayama, Japan

Location

Related Publications (2)

• 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.

  PMID: 41110382 DERIVED

• 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.

  PMID: 36036294 DERIVED

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Interventions

brigatinib

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: January 25, 2018
• Study Start: January 29, 2018
• Primary Completion: September 29, 2020
• Study Completion: July 28, 2021
• Last Updated: May 8, 2024
• Results First Posted: December 14, 2021

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

JP (33)