Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non–Small-Cell Lung Cancer (NSCLC) MedDRA version: 20.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Brigatinib
Product Code: AP26133
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Brigatinib
CAS Number: 1197953-54-0
Current Sponsor code: AP26113
Other descriptive name: AP
Sponsors
ARIAD Pharmaceuticals, Inc.(a wholly-owned subsidiary of Takeda Pharmaceutical Ltd.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have histologically or cytologically confirmed stage IIIB (locally advanced or recurrent and not a participant for curative therapy) or stage IV non–small-cell lung cancer (NSCLC). 2. Must meet both of the following 2 criteria: a. Have documentation of anaplastic lymphoma kinase (ALK) rearrangement by a positive result from any laboratory test® approved by the food and drug administration (FDA) or Have documented ALK rearrangement by a different test (non–FDA-approved local lab tests) and have provided tumor sample to the central laboratory. (Note: Central laboratory ALK rearrangement testing results are not required to be obtained before randomization.) b. Had been on any one of the ALK tyrosine kinase inhibitor (TKIs) (alectinib, ceritinib, crizotinib) for at least 12 weeks before progression. 3. Had progressive disease (PD) while on alectinib or ceritinib 4. Had alectinib or ceritinib as the most recent ALK inhibitor therapy. 5. Have at least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by the investigator. 6. Had recovered from toxicities related to prior anticancer therapy to national cancer institute common terminology criteria for adverse events (NCI CTCAE), version 4.03, Grade =1. (Note: Treatment-related alopecia or peripheral neuropathy that are Grade >1 are allowed if deemed irreversible.) and have adequate major organ functions. 7. Have a life expectancy of =3 months. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 83 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Had received any prior ALK-targeted TKI other than crizotinib, alectinib, or ceritinib. 2. Had received both alectinib and ceritinib. 3. Had previously received more than 3 regimens of systemic anticancer therapy for locally advanced or metastatic disease. 4. Had symptomatic brain metastasis (parenchymal or leptomeningeal). Participants with asymptomatic brain metastasis or who have stable symptoms that did not require an increased dose of corticosteroids to control symptoms in the past 7 days before the first dose of brigatinib may be enrolled. 5. Had current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed. 6. Had a cerebrovascular accident or transient ischemic attack within 6 months before first dose of brigatinib. 7. Had an ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics. 8. Had malabsorption syndrome or other gastrointestinal (GI) illness that could affect oral absorption of brigatinib.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Overall timeframe will be pending on final sample size.;Secondary Objective: 1. To characterize the durability of efficacy with brigatinib. 2. To assess intracranial efficacy of brigatinib. 3. To assess the overall survival (OS). 4. To assess the safety and tolerability of brigatinib. 5. To collect plasma concentration-time data for brigatinib to contribute to population pharmacokinetic analyses. 6. To assess patient-reported symptoms and health-related quality of life (HRQOL).;Main Objective: To determine the efficacy of brigatinib, as evidenced by confirmed objective response rate (ORR), in patients with ALK+ locally advanced or metastatic NSCLC whose disease has progressed on therapy with alectinib or ceritinib as determined by investigator.;Primary end point(s): The primary endpoint is confirmed ORR, as assessed by the IRC, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the full analysis set population. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Confirmed ORR, as assessed by the investigator, per RECIST version 1.1. 2. DOR as assessed by the investigator and IRC. 3. PFS as assessed by the investigator and IRC. 4. Disease control rate (DCR), defined as best overall response of complete response (CR), partial response (PR) or stable disease (SD) =6 weeks by RECIST version 1.1, as assessed by the investigator and IRC. 5. Time to response as assessed by the investigator and IRC. 6. Confirmed iORR in patients with brain metastases at baseline, as assessed by the IRC. 7. Duration of intracranial response in patients with brain metastases at baseline, as assessed by the IRC. 8. Intracranial progression-free survival (iPFS) in patients with brain metastases at baseline, as assessed by the IRC. 9. OS. 10. Safety/tolerability (CTCAE version 4.03). 11. HRQOL assessed with the global health status/quality of life (QOL) and other function and symptom from EORTC QLQ-C30 (version 3.0), and EORTC QLQ-LC13.;Timepoint(s) of evaluation of this end point: Overall timeframe will be pending on final sample size. | — |
Countries
Australia, Austria, Canada, China, France, Germany, Hong Kong, Israel, Italy, Korea, Republic of, Netherlands, Spain, Sweden, Taiwan, United States
Contacts
Public ContactAshwata Pokhrel
Takeda Pharmaceuticals Inc.
Outcome results
None listed