Pembrolizumab Plus Bevacizumab for Treatment of Brain Metastases in Metastatic Melanoma or Non-small Cell Lung Cancer (NSCLC)

Major 1. Biopsy proven metastatic melanoma or non-squamous NSCLC with at least one untreated brain metastasis that is at least 5 mm AND twice the MRI slice thickness, but less than 20 mm, which is asymptomatic and not requiring immediate local therapy or steroids. 2. Patients who have had prior resection or biopsy of a CNS metastasis will be required to provide a paraffin embedded specimen from tumor taken at the time of surgery, if available. 3. Patients will be required to undergo biopsy or submit archival tumor tissue from a systemic site of disease for correlative studies. When not feasible, this requirement can be waived after discussion with the principal investigators. 4. PD-L1 expression in tumor tissue from any site determined by the Dako 22C3 assay is required for patients with NSCLC. 5. Adequate organ function. 6. ECOG performance status \< 2. 7. Any number of previous treatments with the exception of previous inhibitors of PD-1 or PD-L1. 8. Life expectancy of at least 3 months. 9. Understanding and willingness to consent. 10. A history of radiotherapy for brain metastases is allowed, but any lesion present at the time of WBRT or included in the stereotactic radiotherapy field will NOT be considered evaluable unless documented to have progressed since treatment. Overall Inclusion Criteria: 1. Biopsy proven metastatic melanoma or non-squamous NSCLC with at least one untreated cerebral metastasis that is at least 5 mm AND twice the MRI slice thickness, but less than 20 mm, that is asymptomatic and does not require local therapy at the time of enrollment ("clinically evaluable lesion(s)"). An untreated brain metastasis is defined as a lesion not present at the time of whole brain radiation therapy or included in a stereotactic radiotherapy field (or within 2mm of a treated lesion), or any lesion that is new or unequivocally progressing since prior radiation therapy. 2. ECOG performance status \< 2 3. Any number of previous treatments with the exception of previous inhibitors of PD-1, PD-L1, or PD-L2. Other prior systemic therapies must have been administered at least 2 weeks before administration of pembrolizumab; the exception to this is ipilimumab which must have been administered at least 4 weeks prior to the start of pembrolizumab. Patients are not required to have had prior systemic therapy. 4. Life expectancy of at least 3 months 5. A history of previously treated brain metastases is allowed, provided that at least 7 days have lapsed between radiation and initiation of pembrolizumab. Any brain metastasis ≥ 20mm or causing symptoms must be treated with local therapy (i.e. radiation or surgical resection, as clinically appropriate) prior to study enrollment. Any lesion present at the time of WBRT or included in the stereotactic radiotherapy field (or within 2mm of the treated lesion) will NOT be considered evaluable unless it is new or documented to have progressed since treatment. 6. PD-L1 expression \>1% in tumor tissue from any site is required for patients with NSCLC. Tumor tissue can be archival if no intercurrent systemic therapy was administered, however if no archival tissue is available or if intercurrent systemic therapy was administered, then a biopsy must be obtained for PD-L1 testing. PD-L1 expression must be obtained using the Dako 22C3 assay in a CLIA-certified laboratory. PD-L1 expression is not required for patients with melanoma. 7. All patients are required to submit a tumor specimen for analysis (brain or extra-cerebral). A formalin-fixed paraffin-embedded (FFPE) tissue block, or a 4mm punch from an FFPE block must be submitted. If it is not possible to safely obtain a biopsy due to anatomic location of tumors, and no prior tissue is available, this requirement may be waived upon discussion with the study PI or co-PI. 8. Patients must have normal organ and marrow function (as defined in the protocol) at the time of screening. 9. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours 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. 10. 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. 11. 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. Major

1. Symptomatic brain metastases at the time of initiation of systemic therapy. 2. Other systemic therapy within 14 days of initiation of study drug. 3. Use of corticosteroids to control CNS symptoms. Low-dose steroid use (≤10 mg of prednisone or equivalent) is allowed. 4. Presence of leptomeningeal disease. 5. Presence of active autoimmune disease. Autoimmune thyroid disease will be allowed if thyroid function is within normal range. Overall