This research is being done to find out the safety of propranolol and, identify the maximum tolerated dose of propranolol that can be administered in combination with pembrolizumab in patients with unresectable stage III and stage IV melanoma. This study will evaluate this novel combination of pembrolizumab and propranolol to see what effect it may have on how your cancer responds to the treatment combination.

Phase II *propranolol twice a day. *pembrolizumab by an infusion every 3 weeks. *May receive treatment with pembrolizumab and propranolol for up to 24 months from the time they began treatment with the combination. Procedures to be done:.  A medical history  A physical exam  ECOG Performance Status  Perceived Stress Scale questionnaire  An assessment of tumor by scan. Scans may include: o Computed tomography (CT), with or without contrast. o Magnetic resonance imaging (MRI) or head CT with IV contrast  Blood tests: o Approximately 2 tablespoons for routine testing, such as a complete blood count and a comprehensive metabolic panel  Pregnancy test  Urinalysis  Electrocardiogram  A sample of tumor from a previous biopsy or sample taken Phase 1 portion of the study, these evaluations/tests will also occur on Day 8 of Cycle 1  Review concomitant medications.  Physical Exams  ECOG Performance Status  Perceived Stress Scale questionnaire  Blood tests: o Every 3 weeks o At 3 weeks and 6 months or discontinuation of treatment (whichever comes sooner) and at disease progression o Every 3 weeks: Approximately 1 tablespoon for tests that monitor your blood sugar levels and thyroid function o Every week for the first 6 weeks then every cycle for another 6 weeks  Assessment of cancer by CT or MRI. These assessments will be performed every 12 weeks(± 14 days). The first assessment will be after completing Cycle 4. If their cancer is found to be improving, repeat the CT and MRI scans in about 12 weeks.  EKG: Once treatment begins, this will be done every cycle prior to receiving pembrolizumab for the first 5 cycles.  Adverse events  Tumor Biopsy: A tumor biopsy (only in phase II) will be obtained at the 12 weeks after initiation of treatment.Tumor biopsy will be optional for phase II patients.. Safety Follow-Up: After all study treatment has stopped, end of treatment visit, which will be approximately 30 days after their last dose of study drug or before starting a new treatment  Medical History:  Concomitant medications  complete physical examination  ECOG Performance Status  Perceived Stress Scale assessment  Adverse events  Survival status  Blood tests: o Follow- Up Phase 3 Month and 6 Month Follow- up After Treatment blood collected. The following assessments will be performed at 3 months and 6 months after the safety follow-up visit. Review concomitant medications  Physical examination  ECOG Performance Status  Adverse events  Survival Status  Blood tests:  CT of chest, abdomen and pelvis, or other areas as needed Long Term Survival Follow- Up: After your 3 month and 6 month follow up visits or if they progress, will be contacted every 6 months (±30 days)