A Study to Evaluate the Efficacy of Brigatinib (AP26113) in Participants With Anaplastic Lymphoma Kinase (ALK)-Positive, Non-small Cell Lung Cancer (NSCLC) Previously Treated With Crizotinib

NCT02094573 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: AP26113-13-2012013-002134-21U1111-1196-8246
• Study Type: interventional
• Target: 222
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of two different dosing regimens of brigatinib (AP26113) in participants with ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on therapy with crizotinib.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Confirmed Objective Response Rate (ORR) as Assessed by Investigator

  ORR assessed by the investigator, was defined as percentage of the participants with confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST) v1.1 (confirmed ≥4 weeks after initial response), after 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 norrmalization of tumor marker level. PR: at least 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters. The exact 2-sided 97.5% confidence interval was calculated. The treatment regimen was considered to have achieved the primary objective when lower bound of the 97.5% confidence interval for ORR assessed by investigator is greater than 20%.

  Screening, at 8-week intervals thereafter (on Day 1 of every odd-numbered Cycle of 28-days) through 15 Cycles and every 3 Cycles thereafter until disease progression or up to end of the study (approximately up to 69 months)

Secondary Outcomes (13)

• Confirmed Objective Response Rate (ORR) as Assessed by Independent Review Committee (IRC)

  Screening, at 8-week intervals thereafter (on Day 1 of every odd-numbered Cycle of 28-days) through 15 Cycles and every 3 Cycles thereafter until disease progression or up to end of the study (approximately up to 69 months)

• Confirmed Intracranial Central Nervous System Objective Response Rate (CNS ORR) in Participants With Measurable Active Brain Metastases

  Screening, at 8-week intervals thereafter (on Day 1 of every odd-numbered Cycle of 28-days) through 15 Cycles and every 3 Cycles thereafter until disease progression or approximately up to 29 months

• Confirmed Intracranial Central Nervous System Objective Response Rate (CNS ORR) in Participants With Only Non-measurable Active Brain Metastases

  Screening, at 8-week intervals thereafter (on Day 1 of every odd-numbered Cycle of 28-days) through 15 Cycles and every 3 Cycles thereafter until disease progression or approximately up to 29 months

• Intracranial CNS Progression Free Survival (PFS) in Participants With Active Brain Metastases

  Screening, at 8-week intervals thereafter (on Day 1 of every odd-numbered Cycle of 28-days) through 15 Cycles and every 3 Cycles thereafter until disease progression or approximately up to 29 months

• Time to Response

  Up to approximately 69 months

Study Arms (2)

Brigatinib 90 mg

EXPERIMENTAL

Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).

Drug: Brigatinib

Brigatinib 90 mg - 180 mg

EXPERIMENTAL

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 until disease progression or intolerable toxicity (median duration of exposure was 522 days).

Drug: Brigatinib

Interventions

Brigatinib DRUG

Brigatinib tablets

Also known as: AP26113, ALUNBRIG™

Brigatinib 90 mg; Brigatinib 90 mg - 180 mg

Eligibility Criteria

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

You may qualify if:

• Have histologically or cytologically confirmed locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is anaplastic lymphoma kinase (ALK+).
• Must meet one of the following two criteria:
• Have documented ALK rearrangement by a positive result from the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit; or
• Have documented ALK positivity by a different test and tissue available for the Vysis® FISH test. Tissue should be derived preferably from a biopsy taken after progression with crizotinib. If such a sample is not available, testing may be performed with archived tumor tissue.
• Had progressive disease while on crizotinib, as assessed by the investigator or treating physician.
• Have at least 1 measurable lesion per RECIST v1.1. 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 (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0) grade ≤2.
• Are a male or female participants ≥18 years old.
• Have a life expectancy ≥3 months.
• Have adequate organ and hematologic function, as determined by:
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN; ≤5 x ULN is acceptable if liver metastases are present)
• Total serum bilirubin ≤1.5 x ULN (\<3.0 x ULN for participants with Gilbert syndrome)
• Serum creatinine ≤1.5 x ULN
• Serum lipase/amylase ≤1.5 x ULN
• Absolute neutrophil count (ANC) ≥1500/µL

You may not qualify if:

• Received any prior ALK-targeted TKI other than crizotinib.
• Received crizotinib within 3 days of the first dose of brigatinib (Day 1, Cycle 1).
• Received cytotoxic chemotherapy, investigational agents, or radiation within 14 days, except SRS or stereotactic body radiosurgery.
• Received monoclonal antibodies or had major surgery within 30 days of the first dose of brigatinib (Day 1, Cycle 1).
• Have been diagnosed with another primary malignancy within the past 3 years (except for adequately treated non-melanoma skin cancer, cervical cancer in situ, or prostate cancer, which are allowed within 3 years).
• Have symptomatic CNS metastases that are neurologically unstable or require an increasing dose of corticosteroids.
• Have current spinal cord compression.
• Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
• Myocardial infarction (MI) within 6 months prior to the first dose of brigatinib
• Unstable angina within 6 months prior to first dose
• Congestive heart failure (CHF) within 6 months prior to first dose
• History of clinically significant (as determined by the treating physician) atrial arrhythmia
• Any history of ventricular arrhythmia
• Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose
• Have a history or the presence of pulmonary interstitial disease or drug-related pneumonitis.

Sponsors & Collaborators

• Ariad Pharmaceuticals: lead

Related Publications (2)

• Kawata AK, Lenderking WR, Eseyin OR, Kerstein D, Huang J, Huang H, Zhang P, Lin HM. Converting EORTC QLQ-C30 scores to utility scores in the brigatinib ALTA study. J Med Econ. 2019 Sep;22(9):924-935. doi: 10.1080/13696998.2019.1624080. Epub 2019 Jun 25.

  PMID: 31125274 DERIVED

• 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.

  PMID: 29768119 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

brigatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2014
• First Posted: March 24, 2014
• Study Start: June 4, 2014
• Primary Completion: February 29, 2016
• Study Completion: February 27, 2020
• Last Updated: March 15, 2021
• Results First Posted: June 21, 2017

Record last verified: 2021-02