Brigatinib in ALK-positive NSCLC Identified Via Blood-based Assays

• Status: Recruiting
• Trial end date: 2024-03-31
• Target enrollment: 0
• Participant gender: All

Summary

This is single-arm, open-label study design. Patients will receive brigatinib until disease progression, unacceptable toxicity, withdrawal of consent, of death.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ji-youn Han
• Collaborators: Seoul National University Bundang Hospital; Seoul National University Hospital; Severance Hospital

Criteria

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.