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

This is a Phase II study to determine the rate of stabilization or disease improvement from investigational decitabine/cedazuridine (INQOVI) treatment in subjects with BRCA1-Associated Protein-1 (BAP1) Cancer Predisposition Syndrome (CPDS) and subclinical, early-stage mesothelioma. Progression-free survival (PFS) will also be determined for treated subjects, and the treatment safety (toxicity) evaluated....

* 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) \= 2.0 mg/dL * aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \= 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.