Decitabine/Cedazuridine (INQOVI), an Oral DNA Demethylating Agent, in Subjects With BAP1 Cancer Predisposition Syndrome and Subclinical, Early-Stage Mesothelioma

* INCLUSION CRITERIA:
* Participants with history of germline BRCA1-Associated Protein-1 (BAP1) mutations.
* Histologically confirmed by NCI LP subclinical, early-stage (Tx-T1) mesotheliomas.
* Participants with other early-stage BAP1-associated malignancies in addition to subclinical, early-stage mesotheliomas are eligible for study.
* The extent of the disease (Tx by radiographic imaging) must be insufficient to warrant approved front-line therapies (surgery, chemotherapy, immunotherapy) per standard of care (SOC). Participants with cT1 tumors may be eligible for study if they have been offered and have refused front-line SOC treatment.
* Age \>= 18 years.
* Evaluable disease as confirmed by minimally invasive (videoscopic) assessment (thoracoscopy and/or laparoscopy) performed at screening (within 8 weeks prior to treatment initiation).
* Willingness to undergo pre- and post-treatment minimally invasive thoracoscopy and/or laparoscopy to assess treatment response.
* Willingness to co-enroll on 20C0106 (Prospective Evaluation of High Resolution Dual Energy Computed Tomographic Imaging, Noninvasive (Liquid) Biopsies, and Minimally Invasive Surgical Surveillance for Early Detection of Mesotheliomas in Patients with BAP1 Tumor Predisposition Syndrome) and/or 06C0014 (Prospective Evaluation of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies) to enable collection/processing of tumor, blood and normal pleura if applicable per PI.
* ECOG performance status 0 - 1
* Adequate pulmonary reserve evidenced by FEV1 and DLCO \>= 35% predicted on screening pulmonary function testing (PFTs).
* Oxygen saturation \>= 92% on room air by pulse oximetry at screening.
* Adequate renal, hepatic, and hematopoietic function at screening as defined below:

  * leukocytes \>= 3,000/microL
  * absolute neutrophil count \>= 1,500/microL (without transfusion or cytokine support within 2 months prior to study treatment initiation)
  * absolute lymphocyte count \> 800/microL
  * platelets \>=100,000/microL and \< 1,200,000/microL
  * prothrombin time (PT) \<=2 seconds above the upper limit of normal (ULN)
  * total bilirubin \< 1.5 X institutional upper limit of normal OR direct bilirubin \<= 1 ULN for participants with total bilirubin \> 1.5 ULN
  * serum albumin \>= 2.0 mg/dL
  * aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \<= 2.5 X institutional ULN
  * creatinine \<= 1.6 mg/ml OR creatinine clearance (eGFR) \>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal.
* Individuals of child-bearing potential (IOCBP) and those that can father children must agree to use an effective method of contraception (barrier, hormonal, intrauterine device (IUD), surgical sterilization) from the study entry and up to 6 months (IOCBP) or 3 months (those that can father children) after the last dose of the decitabine/cedazuridine.
* Nursing (including breastfeeding) participants must be willing to discontinue nursing from study treatment initiation through 2 weeks after the last dose of the study drug.
* The ability of a participant to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

* Participants with cancers requiring frontline standard of care treatment.
* Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (\< 6 months prior to study treatment initiation), myocardial infarction (\< 6 months prior to study treatment initiation), unstable angina, congestive heart failure (New York Heart Association Classification Class \>= II, serious cardiac arrhythmia, clinically significant bleeding or clinically significant pulmonary embolism.
* Therapeutic anticoagulation within 2 weeks prior to study treatment initiation.
* Active Hepatitis A (HAV), Hepatitis B (HBV) (e.g., HBsAg reactive), or Hepatitis C (HCV) (e.g., HCV RNA \[qualitative\] is detected) at screening.
* History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness.
* Other active infections requiring systemic therapy.
* Active COVID infection.
* Major surgery within 4 weeks prior to study treatment initiation.
* Immunosuppressive medications within 4 weeks prior to study treatment initiation except non-systemic corticosteroids.
* History of prior treatment with a DNA demethylating agent.
* Pregnancy (confirmed with beta human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in IOCBP at screening).
* Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.