Oral Decitabine (ASTX727) and Durvalumab in Recurrent and/or Metastatic Head and Neck Cancer Patients

Inclusion Criteria

• Written informed consent and any locally-required authorization (e.g., HIPAA in the UEU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Age ≥ 18 years at time of study entry or adult male or female (according to age of majority as defined as ≥18 years)
• Histologically confirmed recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) not amenable to therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Patients who refuse radical resection are eligible.
• Tumor progression or recurrence during or after treatment with anti-PD1, anti-PDL1, anti-PDL2, anti-CTLA4, or other immune checkpoint inhibitor where the most recent dose was given within 3 months prior to study registration.
• Must give valid written consent to provide archival FFPE and/or newly acquired tumor tissue for the purpose of establishing baseline PD-L1 status as well as consent to provide on- and/or post-treatment tumor biopsy sample.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
• Life expectancy of > 6 months
• At least 1 lesion that can be accurately measured at baseline as > 10 mm in the longest diameter (except lymph nodes which must have a short axis >15 mm) with CT or MRI and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines.
• Adequate normal organ and marrow function as defined below (within 28 days prior to study registration):
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
• Serum creatinine level 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:

Males:

--Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)

Females:

--Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)

• Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
• Male subjects with a female partner of childbearing potential must commit to true abstinence from heterosexual contact or commit to the use of male condom plus spermicide throughout the course of the study, and avoid fathering a child during the course of the study (including dose interruptions) and for 6 months following the last dose of azacitidine.
• All men and women of childbearing potential must use acceptable methods of birth control throughout the study as described below:

Females of childbearing potential: Recommendation is for at least one highly effective contraceptive methods during the study and must agree to continue using such precautions for 180 days after the last dose of investigational product.

Non-sterilized males : Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use male condom plus spermicide from screening through 180 days after the last dose of investigational product.

-Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and e