Clinical Trials List
Protocol NumberAP26113-13-301
NCT Number(ClinicalTrials.gov Identfier)NCT02737501
2017-03-14 - 2020-11-01
Phase III
Recruiting5
ICD-10C34
Malignant neoplasm of bronchus and lung
ICD-9162.0
Malignant neoplasm of trachea
A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) Versus Crizotinib in Patients With ALK-positive Advanced Lung Cancer
-
Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
-
Sponsor
ARIAD Pharmaceuticals, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yung-Hung Luo Division of Thoracic Medicine
- Chao-Hua Chiu Division of Thoracic Medicine
- Jen-Fu Shih Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
1 Recruiting
Audit
None
Co-Principal Investigator
- JENG-SEN TSENG Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
- TSUNG -YING YANG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
- Sin-Syue Li Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- 廖偉志 Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
- 陳韋成 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Chia-Chi Lin Division of Hematology & Oncology
- 廖斌志 Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- 楊景堯 Division of General Internal Medicine
- 林宗哲 Division of Hematology & Oncology
- 陳冠宇 Division of General Internal Medicine
- 蔡子修 Division of General Internal Medicine
- Jih-Hsiang Lee Division of Hematology & Oncology
- JIN-YUAN SHIH Division of General Internal Medicine
- 許嘉林 Division of General Internal Medicine
- 林育麟 Division of Hematology & Oncology
- Chong-Jen Yu Division of General Internal Medicine
- 廖唯昱 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
ALK-positive advanced lung cancer
Objectives
The primary objective of the study is to compare the efficacy of brigatinib to that of
crizotinib in ALK+ locally advanced or metastatic NSCLC patients naive to ALK
inhibitors, as evidenced by PFS.
The secondary objectives of the study are:
1. To compare the efficacy of brigatinib to that of crizotinib, as evidenced by
confirmed ORR, time to/duration of response, disease control rate (DCR),
and Overall Survival (OS)
2. To compare the efficacy in the CNS of brigatinib to that of crizotinib, as
evidenced by intracranial response and intracranial PFS in those patients
with intracranial CNS metastases at baseline
3. To assess the safety and tolerability of brigatinib in comparison with
crizotinib
4. To determine pharmacokinetic (PK) parameters of brigatinib through
population PK modeling
5. To assess patient-reported symptoms and health-related quality of life
(HRQoL) with the European Organisation for Research and Treatment of
Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 (v3.0) in
patients treated with brigatinib compared to those treated with crizotinib
Test Drug
Brigatinib (AP26113)
Active Ingredient
Brigatinib
Dosage Form
Tablet
Dosage
30mg/tablet ; 90mg/tablet ; 180mg/tablet
Endpoints
Primary Endpoint:
PFS, as assessed by the BIRC, per RECIST v1.1 (Eisenhauer et al, 2009)
Secondary Endpoints:
1. Confirmed ORR, as assessed by the BIRC, per RECIST v1.1
2. Confirmed intracranial ORR as assessed by the BIRC
3. Intracranial PFS, as assessed by the BIRC
4. OS
5. Duration of response, as assessed by the BIRC
6. Time to response, as assessed by the BIRC
7. Disease control rate, as assessed by the BIRC
8. Safety and tolerability
9. Patient-reported symptoms and HRQoL scores, assessed with the EORTC
QLQ-C30 (v3.0)
Exploratory Endpoints:
1. Confirmed ORR for brigatinib, as assessed by the BIRC, per RECIST v1.1,
in patients who crossover from Arm B (crizotinib)
2. PFS from the first dose of brigatinib, as assessed by the BIRC, per RECIST
v1.1, in patients who crossover from Arm B (crizotinib)
3. Correlation of brigatinib plasma PK with both efficacy and safety
4. Molecular determinants of efficacy and safety with brigatinib and crizotinib
PFS, as assessed by the BIRC, per RECIST v1.1 (Eisenhauer et al, 2009)
Secondary Endpoints:
1. Confirmed ORR, as assessed by the BIRC, per RECIST v1.1
2. Confirmed intracranial ORR as assessed by the BIRC
3. Intracranial PFS, as assessed by the BIRC
4. OS
5. Duration of response, as assessed by the BIRC
6. Time to response, as assessed by the BIRC
7. Disease control rate, as assessed by the BIRC
8. Safety and tolerability
9. Patient-reported symptoms and HRQoL scores, assessed with the EORTC
QLQ-C30 (v3.0)
Exploratory Endpoints:
1. Confirmed ORR for brigatinib, as assessed by the BIRC, per RECIST v1.1,
in patients who crossover from Arm B (crizotinib)
2. PFS from the first dose of brigatinib, as assessed by the BIRC, per RECIST
v1.1, in patients who crossover from Arm B (crizotinib)
3. Correlation of brigatinib plasma PK with both efficacy and safety
4. Molecular determinants of efficacy and safety with brigatinib and crizotinib
Inclution Criteria
All patients must meet all of the following eligibility criteria for study entry:
1. Have histologically or cytologically confirmed stage IIIB (and not a
candidate for definitive multimodality therapy) or stage IV NSCLC.
2. Must meet one of the following two criteria:
a. Have documentation of ALK rearrangement by a positive result from
the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH)
Probe Kit or the Ventana ALK (D5F3) CDx Assay. The test must have
been performed according to the product’s instructions for use (IFU).
b. Have documented ALK rearrangement by a different test and adequate
tissue available for central laboratory testing by an FDA-approved test.
Confirmation of central test positivity is not required prior to
randomization.
3. Have sufficient tumor tissue available for central analysis (see the Study
Reference Manual for minimum requirements)
4. Have at least 1 measurable (i.e., target) lesion per RECIST v1.1 (see
Appendix C).
5. Recovered from toxicities related to prior anticancer therapy to NCI CTCAE
v 4.0 grade ≤1.
6. Are a male or female patient ≥18 years old.
7. Have adequate organ function, as determined by:
a. ALT/AST ≤2.5 × upper limit of normal (ULN); ≤5 × ULN is acceptable
if liver metastases are present
b. Total serum bilirubin ≤1.5 × ULN (<3.0×ULN for patients with Gilbert
syndrome)
c. Serum creatinine ≤1.5 × ULN
d. Serum lipase/amylase ≤1.5 × ULN
e. Absolute neutrophil count (ANC) ≥1.5 × 109
/L
f. Platelet count ≥75 × 109
/L
g. Hemoglobin ≥10 g/dL
8. Have Eastern Cooperative Oncology Group (ECOG) performance status <2
(see Appendix B).
9. Have normal QT interval on screening ECG evaluation, defined as QT
interval corrected (Fridericia) (QTcF) of ≤450 milliseconds (msec) in males
or ≤470 msec in females.
10. For female patients of childbearing potential, have a negative pregnancy test
documented prior to randomization.
11. For female and male patients who are fertile, agree to use a highly effective
form of contraception with their sexual partners throughout study
participation (Section 14.3.1).
12. Provide signed and dated informed consent indicating that the patient has
been informed of all pertinent aspects of the study, including the potential
risks, and is willingly participating.
13. Have the willingness and ability to comply with scheduled visit and study
procedures.
1. Have histologically or cytologically confirmed stage IIIB (and not a
candidate for definitive multimodality therapy) or stage IV NSCLC.
2. Must meet one of the following two criteria:
a. Have documentation of ALK rearrangement by a positive result from
the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH)
Probe Kit or the Ventana ALK (D5F3) CDx Assay. The test must have
been performed according to the product’s instructions for use (IFU).
b. Have documented ALK rearrangement by a different test and adequate
tissue available for central laboratory testing by an FDA-approved test.
Confirmation of central test positivity is not required prior to
randomization.
3. Have sufficient tumor tissue available for central analysis (see the Study
Reference Manual for minimum requirements)
4. Have at least 1 measurable (i.e., target) lesion per RECIST v1.1 (see
Appendix C).
5. Recovered from toxicities related to prior anticancer therapy to NCI CTCAE
v 4.0 grade ≤1.
6. Are a male or female patient ≥18 years old.
7. Have adequate organ function, as determined by:
a. ALT/AST ≤2.5 × upper limit of normal (ULN); ≤5 × ULN is acceptable
if liver metastases are present
b. Total serum bilirubin ≤1.5 × ULN (<3.0×ULN for patients with Gilbert
syndrome)
c. Serum creatinine ≤1.5 × ULN
d. Serum lipase/amylase ≤1.5 × ULN
e. Absolute neutrophil count (ANC) ≥1.5 × 109
/L
f. Platelet count ≥75 × 109
/L
g. Hemoglobin ≥10 g/dL
8. Have Eastern Cooperative Oncology Group (ECOG) performance status <2
(see Appendix B).
9. Have normal QT interval on screening ECG evaluation, defined as QT
interval corrected (Fridericia) (QTcF) of ≤450 milliseconds (msec) in males
or ≤470 msec in females.
10. For female patients of childbearing potential, have a negative pregnancy test
documented prior to randomization.
11. For female and male patients who are fertile, agree to use a highly effective
form of contraception with their sexual partners throughout study
participation (Section 14.3.1).
12. Provide signed and dated informed consent indicating that the patient has
been informed of all pertinent aspects of the study, including the potential
risks, and is willingly participating.
13. Have the willingness and ability to comply with scheduled visit and study
procedures.
Exclusion Criteria
Patients meeting any of the criteria below are ineligible for the study:
1. Previously received an investigational antineoplastic agent for NSCLC.
2. Previously received any prior TKI, including ALK-targeted TKIs.
3. Previously received more than 1 regimen of systemic anticancer therapy 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 antineoplastic agent used as
maintenance therapy will be counted as a new regimen. Neo-adjuvant or
adjuvant systemic anticancer therapy will be counted as a prior regimen if
completion of (neo) adjuvant therapy occurred <12 months prior to
randomization.
4. Received chemotherapy or radiation within 14 days of first dose of study
drug, except stereotactic radiosurgery (SRS) or stereotactic body radiation
therapy (SBRT).
5. Received anti-neoplastic monoclonal antibodies within 30 days of the first
dose of study drug.
6. Had major surgery within 30 days of the first dose of study drug, minor
surgical procedures such as catheter placement or minimally invasive
biopsies are allowed.
7. Have been diagnosed with another primary malignancy other than NSCLC,
except for adequately treated non-melanoma skin cancer or cervical cancer in
situ; definitively treated non-metastatic prostate cancer; or patients with
another primary malignancy who are definitively relapse-free with at least
3 years elapsed since the diagnosis of the other primary malignancy.
8. Have symptomatic CNS metastases (parenchymal or leptomeningeal) at
screening or asymptomatic disease requiring an increasing dose of
corticosteroids to control symptoms within 7 days prior to randomization.
Note: If a patient has worsening neurological symptoms or signs due to CNS
metastasis, the patient needs to complete local therapy and be neurologically
stable (with no requirement for an increasing dose of corticosteroids or use
of anticonvulsants) for 7 days prior to randomization.
9. Have current spinal cord compression (symptomatic or asymptomatic and
detected by radiographic imaging). Patients with leptomeningeal disease and
without cord compression are allowed.
10. Be pregnant, planning a pregnancy, or breastfeeding
11. Have significant, uncontrolled, or active cardiovascular disease, specifically
including, but not restricted to:
a. Myocardial infarction (MI) within 6 months prior to the first dose of
study drug
b. Unstable angina within 6 months prior to first dose of study drug
c. Congestive heart failure (CHF) within 6 months prior to first dose of
study drug
d. History of clinically significant atrial arrhythmia (including clinically
significant bradyarrhythmia), as determined by the treating physician
e. Any history of ventricular arrhythmia
f. Cerebrovascular accident or transient ischemic attack within 6 months
prior to first dose of study drug
12. Have uncontrolled hypertension. Patients with hypertension should be under
treatment on study entry to control blood pressure.
13. Have a history or the presence at baseline of pulmonary interstitial disease,
drug-related pneumonitis, or radiation pneumonitis.
14. Have an ongoing or active infection, including, but not limited to, the
requirement for intravenous (IV) antibiotics.
15. Have a known history of human immunodeficiency virus (HIV) infection.
Testing is not required in the absence of history.
16. Have a known or suspected hypersensitivity to brigatinib or its excipients.
17. Have a known or suspected hypersensitivity to crizotinib or its excipients.
18. Have malabsorption syndrome or other gastrointestinal (GI) illness or
condition that could affect oral absorption of the study drug.
19. Have any condition or illness that, in the opinion of the investigator, would
compromise patient safety or interfere with the evaluation of the study drug.
1. Previously received an investigational antineoplastic agent for NSCLC.
2. Previously received any prior TKI, including ALK-targeted TKIs.
3. Previously received more than 1 regimen of systemic anticancer therapy 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 antineoplastic agent used as
maintenance therapy will be counted as a new regimen. Neo-adjuvant or
adjuvant systemic anticancer therapy will be counted as a prior regimen if
completion of (neo) adjuvant therapy occurred <12 months prior to
randomization.
4. Received chemotherapy or radiation within 14 days of first dose of study
drug, except stereotactic radiosurgery (SRS) or stereotactic body radiation
therapy (SBRT).
5. Received anti-neoplastic monoclonal antibodies within 30 days of the first
dose of study drug.
6. Had major surgery within 30 days of the first dose of study drug, minor
surgical procedures such as catheter placement or minimally invasive
biopsies are allowed.
7. Have been diagnosed with another primary malignancy other than NSCLC,
except for adequately treated non-melanoma skin cancer or cervical cancer in
situ; definitively treated non-metastatic prostate cancer; or patients with
another primary malignancy who are definitively relapse-free with at least
3 years elapsed since the diagnosis of the other primary malignancy.
8. Have symptomatic CNS metastases (parenchymal or leptomeningeal) at
screening or asymptomatic disease requiring an increasing dose of
corticosteroids to control symptoms within 7 days prior to randomization.
Note: If a patient has worsening neurological symptoms or signs due to CNS
metastasis, the patient needs to complete local therapy and be neurologically
stable (with no requirement for an increasing dose of corticosteroids or use
of anticonvulsants) for 7 days prior to randomization.
9. Have current spinal cord compression (symptomatic or asymptomatic and
detected by radiographic imaging). Patients with leptomeningeal disease and
without cord compression are allowed.
10. Be pregnant, planning a pregnancy, or breastfeeding
11. Have significant, uncontrolled, or active cardiovascular disease, specifically
including, but not restricted to:
a. Myocardial infarction (MI) within 6 months prior to the first dose of
study drug
b. Unstable angina within 6 months prior to first dose of study drug
c. Congestive heart failure (CHF) within 6 months prior to first dose of
study drug
d. History of clinically significant atrial arrhythmia (including clinically
significant bradyarrhythmia), as determined by the treating physician
e. Any history of ventricular arrhythmia
f. Cerebrovascular accident or transient ischemic attack within 6 months
prior to first dose of study drug
12. Have uncontrolled hypertension. Patients with hypertension should be under
treatment on study entry to control blood pressure.
13. Have a history or the presence at baseline of pulmonary interstitial disease,
drug-related pneumonitis, or radiation pneumonitis.
14. Have an ongoing or active infection, including, but not limited to, the
requirement for intravenous (IV) antibiotics.
15. Have a known history of human immunodeficiency virus (HIV) infection.
Testing is not required in the absence of history.
16. Have a known or suspected hypersensitivity to brigatinib or its excipients.
17. Have a known or suspected hypersensitivity to crizotinib or its excipients.
18. Have malabsorption syndrome or other gastrointestinal (GI) illness or
condition that could affect oral absorption of the study drug.
19. Have any condition or illness that, in the opinion of the investigator, would
compromise patient safety or interfere with the evaluation of the study drug.
The Estimated Number of Participants
-
Taiwan
8 participants
-
Global
270 participants
