SRS Timing With Immune Checkpoint Inhibition in Patients With Untreated Brain Metastases From Non-small Cell Lung Cancer (STICk-IM-NSCLC)

Inclusion Criteria:

• Patients must have 1 to 15 newly diagnosed brain metastases, ≤3 cm in the largest dimension, with at least one metastasis measuring ≥0.5 cm.

• Primary tumor histology must be one confirmed as one of the following:

  • Squamous NSCLC
  • Adenocarcinoma NSCLC
  • Not otherwise specified NSCLC
• Patient must be able and willing to undergo a thin cut MRI at Duke, which is required for study entry.
• Patient must be planned for immunotherapy treatment as their next systemic therapy, including monotherapy or in combination with chemotherapy.
• Patients previously treated with a tyrosine kinase inhibitor (TKI) may be eligible, if a second line (or later) immunotherapy regimen is planned.
• Patients must be asymptomatic or minimally symptomatic, requiring the equivalent of ≤2 mg dexamethasone/day for at least 7 days prior to enrollment.
• Female and male subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in the Duke Contraception Policy.
• Age ≥18 years of age at the time of entry into the study.
• Karnofsky Performance Score (KPS) ≥70.
• Prothrombin and Partial Thromboplastin Times ≤1.2 x normal
• Neutrophil count ≥1000
• Hemoglobin ≥9 g/dl
• Platelet count ≥100,000/µl
• Creatinine ≤1.2 x normal range.

Exclusion Criteria:

• Patients on the equivalent of >2 mg of dexamethasone daily ≤ 7 days before receiving study treatment
• Patients who have previously receive whole brain radiation therapy (WBRT).
• Patients must not have ever received immunotherapy in the stage IV setting. Prior immune therapy as part of treatment for stage I-III disease is allowed assuming an interval >6 months has passed from the completion of that therapy.
• Patients with leptomeningeal disease. However, patients with discrete dural-based lesions may be eligible.
• Females who are pregnant or breast-feeding.
• Patients with an impending, life-threatening cerebral hemorrhage or herniation, based on the assessment from a brain MRI of the study neurosurgeons or their designate.

• Patients with severe, active co-morbidity, defined as follows:

  • Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C)
  • Patients with known immunosuppressive disease or known uncontrolled human immunodeficiency virus infection
  • Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
• Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used:
• Patients with prior, unrelated malignancy requiring current active treatment in the last 3 years with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
• Patients with a known history of hypersensitivity to the physician's choice of immune checkpoint inhibitor, or any components of the inhibitor.
• Patients who have any contraindications to immunotherapy.
• Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months.
• History and/or confirmed pneumonitis, or extensive bilateral lung disease on high resolution/spiral CT scan.