Pembrolizumab and Stereotactic Radiosurgery for Melanoma or Non-Small Cell Lung Cancer Brain Metastases

Inclusion Criteria

• Be willing and able to provide written informed consent/assent for the trial
• Eastern Cooperative Oncology Group (ECOG) performance scale (PS) of 0-1; Karnofsky performance status ≥ 70%
• Patients must have histological diagnosis of melanoma or non-small cell lung cancer (biopsy will be done per standard of care, if needed to prove metastatic melanoma and/or NSCLC as well as for clinically relevant mutation analysis); additional biopsy will be per standard of care
• Patients can be treated either in first line or in the refractory setting; programmed death-ligand 1 (PD-L1) positivity is not required for enrollment
• All melanoma patients may be tested for proto-oncogene B-Raf (BRAF) as part of routine standard of care, but is not a requirement for the trial; all NSCLC patients may be tested for with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) as part of standard of care, but is not a requirement of the trial
• Having gotten prior programmed cell death protein 1 (PD1) therapy is allowed for, especially if they have previously progressed on it; progression may include extra-cranial as well as intra-cranial progression; after progressing on PD1 therapy, intervening chemotherapy and/or targeted therapy (BRAF inhibitors [BRAFi], etc) is allowed; if they are on intervening chemotherapy and/or targeted therapy (BRAFi, etc), they have to have progression intra-cranially and/or extra-cranially and must be off intervening therapy for at least 2 weeks
• Patient must be asymptomatic at time of getting SRS (day 0) on trial; prednisone 1.5 X institutional ULN (creatinine clearance should be calculated per institutional standard)
• Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• Albumin ≥ 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 X 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 partial thromboplastin time (aPTT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 2 weeks prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
• Abstinence is acceptable, if this is the usual life style and preferred contraception for the patient

Exclusion Criteria

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• If they have brain metastases located in the brain stem (including midbrain, pons, or medulla)
• Inability to undergo magnetic resonance imaging (MRI) evaluation for treatment planning and follow-up
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device wit