5-Azacitidine Plus PD-1/PD-L1 Inhibitor With PD-1/PD-L1 Refractory Tumors

Inclusion Criteria: * Written and voluntary informed consent. * At least 18 years of age or older. * Histologically and radiologically confirmed locally advanced or metastatic unresectable solid tumor malignancy for which PD-1 or PD-L1 therapy is already approved by the FDA. Locally advanced is defined as unresectable in the opinion of the treating physician. A repeat biopsy is required if previous biopsy tissue is unavailable. * At least one Response Evaluation Criteria in Solid Tumors (RECIST 1.1) - defined target lesion. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry on all pre-disease performance without restriction), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as light housework or office work), or 2 (ambulatory and capable of self-care but unable to carry out any work activities, spending more than 50% of waking hours up and about). * Documented progression on PD1 or PD-L1 inhibitors. * Recovery from any acute toxicity associated with prior therapy to grade 1. * Renal function (creatinine level within normal institutional limit, or creatinine clearance \>15 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, calculated using the Cockcroft-Gault formula). * Liver function (AST/ALT \<3.0 X institutional upper limit of normal OR \<5 X institutional upper limit of normal in cases of liver metastasis; total bilirubin ≤ 1.5 times upper limit of normal). * Adequate hematological lab values including: * Absolute Neutrophil Count (ANC) ≥ 1.0 X 109/L * Platelets ≥ 100X109/L * Hemoglobin ≥ 7.0 g/dL * Female subjects of childbearing potential and non-sterilized male subjects who intend to be sexually active during the study must agree to use a highly effective method of contraception from time of screening, throughout the whole duration of the drug treatment, and during the 6-month post-treatment washout period. * Patients may have previously received a hypomethylating agent, as long as it was not given in combination with ipilimumab. * Patients may have previously received ipilimumab but must have relapsed or progressed while on therapy. * Patients must have adequate archival tissue available for the purpose of downstream methylation status assessment, immunohistochemistry, RNA expression (10 slides at 5µM). If archival tissue is not available, a repeat biopsy is required. Exclusion Criteria: * Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen. * Patients with active, untreated metastases in the central nervous system. * Patients who are pregnant or breastfeeding. * Patients who have an active infection. * Patients with significant hematologic, hepatic, and renal function impairment. * Patients who are being treated for any concurrent medical condition requiring the use of systemic steroids or history of long-term use of systemic steroids. * Patients who have a history of inflammatory bowel disease or a history of symptomatic autoimmune disease. * Patients who have had any major surgical procedure or significant traumatic injury within 28 days prior to study enrollment. * Patients who have received chemotherapy, immunosuppressive agents or any investigational drug within 28 days prior to starting the study drugs. * Patients who have any underlying medical condition which, in the treating physician's opinion, will make the administration of study drugs hazardous or obscure the interpretation of adverse events.