| Eligibility |
Inclusion Criteria:
1. The participant(or legally acceptable representative if applicable) provides written
informed consent for the study
2. Patients who have disease progression with prior one ALK-TKI treatment for inoperable
Stage III (locally advanced) or metastatic ALK+ NSCLC.(Previous treatment only allowed
one ALK-inhibitor) Patients who have received prior neo-adjuvant, adjuvant
chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for
non-metastatic disease must have experienced a treatment-free interval of at least 6
months since the last chemotherapy, radiotherapy, or chemoradiotherapy cycle.
3. ALK rearrangement , as detected via the blood somatic mutation assay
4. One prior ALK inhibitor therapy
5. Have at least 1 measurable lesion per RECIST version 1.1
6. Have Eastern Cooperative Oncology Group (ECOG) performance status 0-2
7. Recovered from toxicities related to prior anticancer therapy to NCI CTCAE, version
5.0, Grade=1(Note : Alopecia, sensory neuropathy Grade=2, or other Grade=2 AEs not
constituting a safety risk based on Investigator's judgement are acceptable
8. Have a life expectancy of =3 months
9. Have adequate organ and hematologic function as determined by:
1. ALT/AST=2.5×ULN; =5×ULN is acceptable if liver metastases are present
2. Total serum bilirubin=1.5×ULN (<3.0×ULN for patients with Gilbert syndrome)
3. Estimated glomerular filtration rate (eGFR) =30 mL/min/1.73 m2, using the MDRD
equation
4. Absolute neutrophil count =1.5×109/L.
5. Platelet count =75×109/L.
6. Hemoglobin =9 g/dL.
7. Serum lipase =1.5×ULN
10. For female patients of childbearing potential, have a negative pregnancy test(urine or
serum) documented =3 days before start of study medication.
non-childbearing potential which is defined as :
- female patient=45 years of age and has not had menses for greater than 1 year
- a female who is status post hysterectomy, oophorectomy
11. Female patients of childbearing potential and male patients with partners of
childbearing potential must agree to use 2 effective methods of contraception, 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 completely abstain from heterosexual
intercourseHave the willingness and ability to comply with scheduled visit and study
procedures.
Male patients, even if surgically sterilized (i.e., status post-vasectomy), 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 completely abstain from heterosexual intercourse
12. Have the willingness and ability to comply with scheduled visit and study procedures.
13. Be = 18 years of age
Exclusion Criteria:
1. Has received ALK-targeted TKI within 7 days before the first dose of study
treatment(If clinically justified, 3 days wash-out period could be allowed).
2. Has received radiotherapy within 14 days before the first dose of study treatment
except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy
(SBRT). A 1-week washout is permitted for palliative radiation(=2 weeks of
radiotherapy) to non-CNS disease.
3. Had major surgery within 28 days of the first dose of study treatment. Minor surgical
procedures are allowed.
4. Has symptomatic brain metastasis or leptomeningeal disease. Prior brain metastasis or
leptomeningeal disease allowed if asymptomatic or stable symptoms that did not require
an increased dose of corticosteroids to control symptoms within 7 days prior to study
enrollment. If patients have neurological symptoms or signs due to CNS metastasis,
patients need to complete whole brain radiation or stereotactic radiosurgery treatment
before enrollment and be clinically stable.
5. Has current spinal cord compression
6. Other malignancy within 3 years, except for adequately treated carcinoma in situ of
the cervix, basal or squamous cell skin cancer, localized prostate cancer treated
surgically with curative intent, and ductal carcinoma in situ treated surgically with
curative intent
7. Any gastrointestinal (GI) disorder that may affect absorption of oral medications,
such as malabsorption syndrome or status post-major bowel resection
8. Have significant, uncontrolled, or active cardiovascular disease, specifically
including, but not restricted to:
1. Myocardial infarction within 6 months before the first dose of brigatinib.
2. Unstable angina within 6 months before first dose of brigatinib.
3. Congestive heart failure within 6 months before first dose of brigatinib.
4. History of clinically significant atrial arrhythmia (including clinically
significant bradyarrhythmia).
5. Any history of clinically significant ventricular arrhythmia.
9. Has uncontrolled hypertension.
10. Had a cerebrovascular accident or transient ischemic attack within 6 months before
first dose brigatinib.
11. Have a history or the presence of pulmonary interstitial disease, drug-related
pneumonitis, or radiation-related pneumonitis
12. Active infection requiring systemic therapy.
13. Known history of HIV infection.
14. Has a known or suspected hypersensitivity to brigatinib or its excipients.
15. Female patients who are both lactating and breastfeeding or have a positive serum
pregnancy test during the screening period or a positive urine pregnancy test on Day 1
before first dose of study drug (if applicable).
16. Have any condition or illness that, in the opinion of the investigator, would
compromise
17. patient safety or interfere with the evaluation of brigatinib
18. Received systemic treatment with strong cytochrome P-450 (CYP)3A inhibitors, strong
CYP3A inducers, or moderate CYP3A inducers within 14 days before enrollment.
|
