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

Major Inclusion Criteria:

• 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.
• 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.
• 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.
• PD-L1 expression in tumor tissue from any site determined by the Dako 22C3 assay is required for patients with NSCLC.
• Adequate organ function.
• ECOG performance status 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.
• 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.
• Patients must have normal organ and marrow function (as defined in the protocol) at the time of screening.
• 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.
• 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.

Major Exclusion Criteria:

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

Overall Exclusion Criteria:

• Symptomatic brain metastases. Any neurologic symptoms present must have resolved with local therapy by the time of administration of study drug.
• Patients with brain metastases for whom complete surgical resection is clinically appropriate.
• Patients with lung cancer with squamous histology.
• Has had prior chemotherapy or targeted small molecule therapy within 2 weeks prior to start of treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Previous radiation to extracranial sites may be completed at any time prior to initiation of pembrolizumab.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Note: Toxicity that has not r