Clinical Trial Finder

Inclusion Criteria:

1. Patients must have 1 to 15 newly diagnosed brain metastases, ≤5 cm in the largest dimension, with at least one metastasis measuring ≥0.3 cm. 2. Primary tumor histology must be one confirmed as one of the following: 1. Squamous NSCLC. 2. Adenocarcinoma NSCLC. 3. Not otherwise specified NSCLC. 3. Patient must have an MRI of the brain within 4 weeks (28 days) of signing the study consent. 4. Patient must be planned for immunotherapy treatment as their next systemic therapy, including monotherapy or in combination with chemotherapy. 5. Patients previously treated with a tyrosine kinase inhibitor (TKI) may be eligible, if a second line (or later) immunotherapy regimen is planned. 6. Patients must be asymptomatic or minimally symptomatic, requiring the equivalent of ≤2 mg dexamethasone/day for at least 7 days prior to enrollment. 7. Female and male subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in the Duke Contraception Policy. 8. Age ≥18 years of age at the time of entry into the study. 9. Karnofsky Performance Score (KPS) ≥70.

Exclusion Criteria:

1. Patients on the equivalent of >2 mg of dexamethasone (or prednisone/steroid equivalent) daily ≤ 7 days before receiving study treatment. 2. Patients who have previously received whole brain radiation therapy (WBRT). 3. 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 after an interval of >6 months has passed from the completion of that therapy. 4. Patients with leptomeningeal carcinomatosis. However, patients with discrete dural-based lesions may be eligible at the discretion of the treating radiation oncologist. 5. Females who are pregnant or breastfeeding. 6. Patients with an impending, life-threatening cerebral hemorrhage or herniation, based on the assessment from a brain MRI of the study neurosurgeons or their designee. 7. Patients with severe, active co-morbidity, defined as follows: 1. Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C) 2. Patients with known immunosuppressive disease or known uncontrolled human immunodeficiency virus infection. 3. Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4) 8. 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. 9. Patients with prior, unrelated malignancy requiring current active treatment in the last 3 years with the exception of cervical carcinoma in situ, prostate cancer at stage I-III and adequately treated basal cell or squamous cell carcinoma of the skin. 10. Patients with a known history of hypersensitivity to the physician's choice of immune checkpoint inhibitor, or any components of the inhibitor. 11. Patients who have any contraindications to immunotherapy. 12. Patients with active autoimmune disease requiring systemic immunomodulatory treatment, including steroid of >10 mg prednisone daily or equivalent, within the past 3 months.

Arms

Experimental: Immediate SRS followed by IO

Participants will receive SRS followed by physician's choice of standard of care immunotherapy, given at the FDA-approved dose within 14 days of SRS.

Experimental: Immediate IO followed by SRS

Participants will receive physician's choice of immunotherapy, given at the FDA-approved dose followed by SRS, if deemed appropriate, at the time of intracranial progression.

Interventions

Radiation: - Stereotactic Radiosurgery

Timing of stereotactic radiosurgery relative to immunotherapy

Drug: - Immunotherapy

Physician's choice of immunotherapy per standard of care