Low Dose Ipilimumab With Pembrolizumab in Treating Patients With Melanoma That Has Spread to the Brain

Inclusion Criteria

• Life expectancy > 12 weeks.
• Subjects must have signed and dated an IRB/IEC (Institutional Review Board/Independent Ethics Committee) approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
• Histologically confirmed malignant melanoma with measurable metastases in the brain (>= 0.5 cm).
• At least one measurable intracranial target lesion, which previously was not treated with local therapy (no prior stereotactic radiosurgery [SRS] to this lesion). Largest diameter of >= 0.5 cm, but = = 2 weeks before the start of dosing for this study.
• Prior radiation to non-central nervous system (non-CNS) is allowed, and does not require a washout period for treatment initiation.
• Subjects must be free of neurologic signs and symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroid therapy in the 10 days prior to beginning protocol therapy.
• ECOG (Eastern Cooperative Oncology Group) performance status = = 1500/uL.
• Platelets >= 100,000/uL.
• Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L.
• Creatinine = = 30 L/min with creatinine levels > 1.5 x institutional ULN. GFR (glomerular filtration rate) can also be used in place of creatinine or CrCl (creatinine clearance).
• Total bilirubin = 1.5 x ULN.
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) = 5 lesions in the brain
• Brain lesion size > 3 cm.
• Prior checkpoint inhibitor therapy. Allowable prior therapy: Approved adjuvant therapies, which may include molecularly-targeted agents, IFN-·, and ipilimumab.
• Patients who received ipilimumab as adjuvant or neoadjuvant therapy must have a 6 month washout before receiving any dosing on this study.
• Cohort A: Prior anti-PD in the adjuvant setting is allowed, but washout period is 6 months.
• For Cohort B: Patients with unresectable metastatic melanoma who received either anti-PD-1 or PDL-1 in the past are eligible. Washout period a minimum 3 weeks.
• Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled.
• Subject has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Note: The time requirement does not apply to participants who underwent successful treatment of superficial bladder cancer, in situ cervical cancer, or other in-situ cancers. Subjects with a completely treated prior malignancy and no evidence of disease for >= 2 years are eligible.
• Skin cancer exclusion: Please note that basal cell carcinoma and squamous cell carcinoma is exempt from needing resection prior to treatment. (Resection can be completed after the start of treatment).
• Has a known history of or is positive for hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (hepatitis C virus [HCV] ribonucleic acid (RNA) [qualitative] is detected). Note: Without known history, testing needs to be performed to determine eligibility. Hepatitis C antibody (Ab) testing is allowed for screening purposes in countries where HCV RNA is not part of standard of care.
• Has a known history of human immunodeficiency virus (HIV) infection. No HIV tes