Testing the Addition of an Anti-cancer Drug, ASTX727 (Cedazuridine, Decitabine), to Chemotherapy (Paclitaxel) and Immunotherapy (Pembrolizumab) for Metastatic Triple-Negative Breast Cancer

Exclusion Criteria

• •Patients with prior history of peripheral neuropathy are allowed if it has recovered to grade 1 or less.
• •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
• •Patients who have received 0-3 prior lines of chemotherapy in the metastatic setting. Patients who have received prior PD-1/PD-L1 monoclonal antibodies in any disease setting are eligible.
• •For enrollment to Dose Finding Cohort: Availability and willingness to provide archival tumor tissue as required per protocol.
• •For enrollment to Dose Expansion Cohort: (i) Willingness to provide baseline and 3-week tumor tissue biopsy specimens. (ii) Patients must have a measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• •The effects of ASTX727 and pembrolizumab (MK-3475) on the developing human fetus are unknown. For this reason and because these agents as well as other therapeutic agents used in this trial 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, for the duration of study participation, and 180 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Pregnant women are excluded from this study because pembrolizumab (MK-3475) is an anti PD-1 monoclonal antibody agent, ASTX727 is a hypomethylating agent, and paclitaxel is a class D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab (MK-3475), breastfeeding should be discontinued if the mother is treated with pembrolizumab (MK-3475). These potential risks may also apply to other agents used in this study. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 180 days after completion of study treatment.
• •Ability to understand and the willingness to sign a written informed consent document (or have legally acceptable representative sign, if applicable).
• •Patients who have recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia.
• •* Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• •Has not received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor \[G-CSF\], granulocyte macrophage colony-stimulating factor \[GM-CSF\], or recombinant erythropoietin) within 4 weeks prior to registration.
• •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within the 7 days prior to registration.
• •Has a known additional malignancy that is progressing or requires active treatment.
• •Has an active autoimmune disease that has required systemic treatment within 2 years prior to registration (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Current treatment with systemic steroids up to 10 mg of prednisone daily or equivalent is allowed.
• •Patients with uncontrolled intercurrent illness (including but not limited to interstitial lung disease or active, non-infectious pneumonitis) or a history of (non-infectious) pneumonitis that required steroids.
• •History of grade 3-4 immediate hypersensitivity reaction to paclitaxel or other drugs formulated in polyoxyl 35 castor oil.
• •Patients who are receiving any other investigational agents.
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to ASTX727, pembrolizumab (MK-3475), and/or paclitaxel.
• •Has a known history of active tuberculosis (TB).
• •Gastrointestinal disorder that may impact absorption of oral medications.
• •History of solid organ or bone marrow transplantation.