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 theduration of the study.

3. Be a male or female aged 18-100.

4. Histologically confirmed diagnosis of advanced mucosal melanoma (unresectable StageIII or Stage IV Melanoma). Anatomical locations for primary site of mucosal melanomainclude oral cavity (excluding lip), nasopharynx, vagina/vulva, and rectum.

5. Prior immune checkpoint blockade therapy, including anti-PD1 and anti-CTLA4 forunresectable locally advanced or metastatic disease, is allowed. The combination ofanti-PD1 and anti-CTLA4 is also allowed as a prior line of therapy. Study therapymust 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, orclinically measurable disease.

7. Previously treated brain metastatic disease is allowed. Stability of brainmetastases 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 thefollowing: ANC ≥ 2,500 microliter (mcL); platelets ≥ 100,000/mcL; Hemoglobin ≥ 10g/dL.

10. Patients must have adequate hepatic function as evidenced by the following: totalbilirubin ≤ 1.5 x institutional upper limit of normal (IULN) (except Gilbert'sSyndrome, 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 ≥ 40mL/min.

12. Patients known to be HIV positive are eligible if they meet the following criteriawithin 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-viraltherapy so long as they meet the CD4 count criteria.

13. Women of childbearing potential must have a negative urine or serum pregnancy testwithin 72 hours prior to receiving the first dose of study medication. Women/men ofreproductive potential must have agreed to use an effective contraceptive method forthe 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 partneris participating in this study, she should inform her treating physicianimmediately. A woman is considered to be of "reproductive potential" as defined insection 5.3.2.

14. Patients must be willing to have archived tumor specimens utilized for correlativestudies 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 notin the subject's best interest, or the patient refuses biopsy during course of thestudy, patients will be allowed to remain on study.

Exclusion Criteria:

1. No other prior malignancy is allowed except for the following: adequately treatedbasal cell or squamous cell skin cancer, in situ cervical cancer, lobular carcinomaof the breast in situ, atypical melanocytic hyperplasia or melanoma in situ, treatedand stable thyroid cancer, adequately treated Stage I cancer (including multipleprimary melanomas) from which the patient is currently in complete remission, or anyother 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 daysof enrollment is not permitted. Inhaled or topical steroids, and adrenal replacementsteroid doses ≤10 mg daily prednisone equivalent, are permitted in the absence ofactive 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 systemictreatment in past 2 years from date of enrollment (i.e., with use of diseasemodifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy foradrenal or pituitary insufficiency, etc.) is not considered a form of systemictreatment.

8. Patients must not have a history of (non-infectious) pneumonitis that requiredsteroids 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 killedvirus 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 orlaboratory abnormality that might confound the trial results, interfere with thepatient's participation for the full duration of the trial, or indicate thatparticipation in the trial is not in the patient's best interests, in the opinion ofthe treating investigator.

11. Patients must not be pregnant or lactating.

12. Treatment with any investigational agent within 30 days of first administration ofstudy treatment is not permitted.