Multiple Adjunct Therapies to Improve Immunotherapy Treatment in Patients With Locally Advanced or Metastatic Melanoma or Advanced Hepatocellular Cancer

PRIMARY OBJECTIVE: I. Compare levels of biomarkers of immunomodulation, specifically interleukin (IL)-8, interferon gamma (IFN-y), effector T cells (Teff)/regulatory T cell (Treg) ratio, over a 12-week period, in peripheral blood of patients undergoing standard of care PD-1/PD-L1-containing immunotherapy regimens for advanced cancers randomized to Arm A or Arm B. SECONDARY OBJECTIVE: I. Evaluate the safety and tolerability of the combination of: magnesium, vitamin D supplements; desloratadine; propranolol in patients undergoing morning infusion of standard of care PD-1/PD-L1-containing immunotherapy regimens in Arm A. EXPLORATORY OBJECTIVES: I. Compare additional biomarkers of immunomodulation (including \[incl.\] cytokines, metabolites, select metal ion levels, flow cytometry, circulating tumor deoxyribonucleic acid \[ctDNA\]) over a 12-week period, in peripheral blood of patients undergoing standard of care PD-1/PD-L1-containing immunotherapy regimens for advanced cancers randomized to Arm A or Arm B. II. Compare the preliminary clinical benefit using time to next treatment (TTNT) in patients undergoing standard of care PD-1/PD-L1-containing immunotherapy regimens for advanced cancers randomized to Arm A or Arm B. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive standard of care PD-1/PD-L1-containing immunotherapy infusion, starting before 12 PM, desloratadine orally (PO) once daily (QD), propranolol PO twice daily (BID), magnesium intravenously (IV) if magnesium level is below 1.9, and vitamin D PO QD if vitamin D level is below 30. Additional IV or oral magnesium and vitamin D supplementation may be administered at the investigator's discretion per standard of care. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) and blood sample collection throughout the study. ARM B: Patients receive standard of care PD-1/PD-L1-containing immunotherapy, starting at standard of care time. Magnesium and vitamin D levels are checked with any supplementation per investigator discretion and institutional practice, without a prespecified goal level. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months.