ASTX727 for the Treatment of Advanced, Unresectable, or Metastatic Solid Tumors

Inclusion Criteria

• Participants must have advanced, unresectable, and/or metastatic solid tumor malignancy that is histologically or cytologically confirmed
• Patients must have received at least 2 lines of therapy in the advanced/metastatic setting (if 2 lines exist) and have no other possible therapies or refuse therapies that have shown clinical benefit for their condition
• Patients must have measurable disease per RECIST 1.1 * Patients with biopsiable disease must be amenable to mandatory research biopsies
• Archival tissue must be procured if available
• Life expectancy of greater than 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin < 3 X institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5.0 X institutional upper limit of normal with liver metastases or AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal without liver metastases
• Creatinine < 1.5X institutional upper limit of normal or creatinine clearance >= 50 mL/min/1.73 m^2 for subjects with creatinine levels above institutional normal
• The effects of ASTX727 on the developing human fetus are unknown. For this reason and because oncological agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men should be advised not to father a child while receiving treatment with cedazuridine, decitabine, the combination product ASTX727, and for 60 days after completion of treatment
• Ability to understand and the willingness to sign a written informed consent document
• Ability to swallow oral medications
• Human immunodeficiency virus (HIV)-Patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must have: * A stable regimen of highly active anti-retroviral therapy (HAART) not including drugs known to be metabolized by CDA * No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections * A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based test

Exclusion Criteria

• Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events =< grade 1 (=< grade 2 for sensory neuropathy) due to agents administered more than 3 weeks earlier
• Participants may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical to decitabine or ASTX727
• Subjects who have received prior therapy with any hypomethylating agents
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because ASTX727 is a hypomethylating agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with ASTX727, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study
• Drugs known to be metabolized by CDA (e.g., cytarabine, gemcitabine, azacytidine, vidarabine, zalcitabine, zidovudine, telbivudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, entecavir, apricitabine, idoxuridine, trifluridine, tenofovir and adefovir) should not be administered with ASTX727
• Active hepatitis B or hepatitis C infection
• Active or untreated gastric or duodenal ulcer
• Hospitalization for an acute medical issue within 4 weeks prior to screening visit that would otherwise not be managed in an infusion center or outpatient clinic setting (e.g., a patient admitted to complete a transfusion would not be ineligible)
• Symptomatic bowel obstruction within 3 months prior to screening visit
• Symptomatic ascites in the last 4 weeks (requiring a paracentesis or causing discomfort)