Oral Decitabine/Cedazuridine (DEC-C) in Combination With Nivolumab for Patients With Mucosal Melanoma

Inclusion Criteria: 1. Provision to sign and date the consent form. 2. Stated willingness to comply with all study procedures and be available for the duration of the study. 3. Be a male or female aged 18-100. 4. Histologically confirmed diagnosis of advanced mucosal melanoma (unresectable Stage III or Stage IV Melanoma). Anatomical locations for primary site of mucosal melanoma include oral cavity (excluding lip), nasopharynx, vagina/vulva, and rectum. 5. Prior immune checkpoint blockade therapy, including anti-PD1 and anti-CTLA4 for unresectable locally advanced or metastatic disease, is allowed. The combination of anti-PD1 and anti-CTLA4 is also allowed as a prior line of therapy. Study therapy must be initiated within 30 days of previous immune checkpoint blockade therapy (excluding adjuvant anti-PD1 and anti-CTLA4). 6. Patients must have systemic cross-sectional imaging (PET/CT or CT of chest, abdomen, and pelvis) with radiographically measurable, by immune-RECIST (RECIST) criteria, or clinically measurable disease. 7. Previously treated brain metastatic disease is allowed. Stability of brain metastases must be confirmed by MRI \> 4 weeks from most recent treatment and within 4 weeks of initiating study therapy. 8. Patients must have an ECOG performance status of 0 or 1 (Table 5). 9. Patients must have adequate bone marrow function as evidenced by all of the following: ANC ≥ 2,500 microliter (mcL); platelets ≥ 100,000/mcL; Hemoglobin ≥ 10 g/dL. 10. Patients must have adequate hepatic function as evidenced by the following: total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) (except Gilbert's Syndrome, who must have a total bilirubin \< 3.0 mg/dL), and SGOT (AST) and SGPT (ALT) and alkaline phosphatase ≤ 2.5 x ULN. 11. Patients must have adequate renal function as evidenced by ONE of the following: serum creatinine ≤ 2.0 x ULN OR measured or calculated creatinine clearance ≥ 40 mL/min. 12. Patients known to be HIV positive are eligible if they meet the following criteria within 30 days prior to registration: stable and adequate CD4 counts (≥ 350 mm3), and serum HIV viral load of \< 25,000 IU/ml. Patients may be on or off anti-viral therapy so long as they meet the CD4 count criteria. 13. Women of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. Women/men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. A woman is considered to be of "reproductive potential" as defined in section 5.3.2. 14. Patients must be willing to have archived tumor specimens utilized for correlative studies if available. 15. Patients must consent to have biopsies performed prior to treatment and around cycle 2 during study. However, in the event that tumor is inaccessible, the biopsy is not in the subject's best interest, or the patient refuses biopsy during course of the study, patients will be allowed to remain on study. Exclusion Criteria: 1. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, lobular carcinoma of the breast in situ, atypical melanocytic hyperplasia or melanoma in situ, treated and stable thyroid cancer, adequately treated Stage I cancer (including multiple primary melanomas) from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years. 2. Patients must not currently be on other drugs metabolized by CDA. 3. Prior cytotoxic chemotherapy treatment received within 30 days of study enrollment. 4. Patients with leptomeningeal disease. 5. Current immunosuppressive therapy including \>10mg/day of prednisone within 14 days of enrollment is not permitted. Inhaled or topical steroids, and adrenal replacement steroid doses ≤10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. 6. Patients must not have known active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection prior to registration. 7. Patients must not have active autoimmune disease that has required systemic treatment in past 2 years from date of enrollment (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 8. Patients must not have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 9. Patients must not have received live vaccines within 42 days prior to enrollment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza and COVID-19 vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. 10. Patients must not have a history or current evidence of any condition, therapy or laboratory abnormality that might confound the trial results, interfere with the patient's participation for the full duration of the trial, or indicate that participation in the trial is not in the patient's best interests, in the opinion of the treating investigator. 11. Patients must not be pregnant or lactating. 12. Treatment with any investigational agent within 30 days of first administration of study treatment is not permitted.