Local Consolidative Therapy and Brigatinib in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer

Korábbi kezelés

• Previously received any prior TKI, including ALK-targeted TKIs. Note: on-going first-line brigatinib use as specified in the Inclusion criteria is allowed.
• Previously received more than 1 regimen of chemotherapy or immunotherapy for locally advanced or metastatic disease. Note that history of consolidative immunotherapy after concurrent chemoradiotherapy (for locally advanced disease) is allowed.
• Symptomatic CNS metastasis. Asymptomatic CNS disease requiring increasing dose of corticosteroids within 7 days prior to study enrollment is also not permitted.
• 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 study drug
  • Unstable angina within 6 months prior to first dose of study drug
  • Decompensated congestive heart failure (CHF) within 6 months prior to first dose of study drug
  • History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician
  • Any history of ventricular arrhythmia
  • Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose of study drug

Más betegség

• 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 2 years elapsed since the diagnosis of the other primary malignancy.
• Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression are allowed.
• The presence of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis at screening.
• Have a known or suspected hypersensitivity to brigatinib or its excipients.
• Have malabsorption syndrome or other gastrointestinal (GI) illness or condition that could affect oral absorption of the study drug.
• Have uncontrolled hypertension. Patients with hypertension should be under treatment on study entry to control blood pressure
• Have an ongoing or active infection, including, but not limited to, the requirement for intravenous (IV) antibiotics.
• Have a known history of human immunodeficiency virus (HIV) infection. Testing is not required in the absence of history.
• 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.

Egyéb

• Be pregnant, planning a pregnancy, or breastfeeding.

• Histologically or cytologically confirmed diagnosis of stage IV NSCLC (or recurrent NSCLC not a candidate for definitive multimodality therapy)
• Documented ALK re-arrangement as detected by: (1) FISH, (2) IHC, (3) tissue NGS, or (4) cfDNA NGS
• Subjects can be enrolled as (1) TKI naïve or (2) after ≤ 8 weeks of first-line brigatinib treatment without disease progression.
• Candidate for local consolidative therapy to at least one site of residual disease
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Males or females aged at least 18 years.
• Adequate organ function laboratory values, defined as:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L or at least 1500/mm3 or at least 1.5 x 109/L
  • Platelet count at least 75,000/mm3 or at least 75 x 109/L
  • Hemoglobin (Hb) at least 9 g/dL (or 5.69 mmol/L) at baseline
  • Serum creatinine ≤ 1.5 × ULN or ≥ 60 mL/minute for subjects with creatinine levels \> 1.5 × the institutional ULN
  • Serum total bilirubin less than or equal to ≤ 1.5 × ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 × ULN
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN except for subjects with liver mets for whom ALT and AST should be ≤ 5× ULN
  • International Normalized Ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated PTT (aPTT) ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulant
• Female patients of childbearing potential must have a negative pregnancy test documented at time of screening.
• Female patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to use a highly effective method of contraception 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 intercourse
• 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
• 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.
• Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.