Study of SX-682 Alone and in Combination with Oral or Intravenous Decitabine in Subjects with Myelodysplastic Syndrome

Inclusion Criteria

• Diagnosis of MDS by World Health Organization criteria, and either
• International Prognostic Scoring System (IPSS) low risk or intermediate-1 risk patients without 5q deletion: i. Dose escalation portion: failed prior treatment with at least 4 cycles started of a hypomethylating agent (HMA; azacitidine or decitabine) defined as no response to treatment, loss of response at any time point, or progressive disease/intolerance to therapy. ii. Dose expansion portion: failed prior treatment defined as no response to treatment with at least 4 cycles started of HMA, loss of response at any time point, or progressive disease/intolerance to therapy ("HMA failure"); or no prior treatment with HMA ("HMA naive").
• IPSS low risk or intermediate-1 risk patients with 5q deletion: i. Dose escalation portion: failed prior treatment with at least 4 cycles started of lenalidomide and 4 cycles of hypomethylating agent (azacitidine or decitabine) defined as no response to treatment, loss of response at any time point, or progressive disease/intolerance to therapy. ii. Dose expansion portion: same as non-del(5q) lower risk cohort + requirement of failed prior treatment with lenalidomide defined as no response to treatment with at least 4 cycles started of lenalidomide, loss of response at any time point, or progressive disease/intolerance to therapy.
• IPSS intermediate-2 risk or high risk patients: HMA failure or HMA naïve as defined above.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• Screening laboratory values:
• Renal glomerular filtration rate (GFR) ≥ 30 ml/min;
• Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) ≤ 3.0 times upper limit of normal;
• Bilirubin < 1.5 times upper limit of normal;
• No history of HIV being HIV positive;
• No active Hepatitis B or Hepatitis C infection.
• Life expectancy ≥ 12 weeks.
• Women of childbearing potential (WOCBP) must use study specified contraception.
• WOCBP demonstrate negative pregnancy test.
• Not breastfeeding.
• Men sexually active must use study specified contraception.

Exclusion Criteria

• Use of chemotherapeutic agents or experimental agents for MDS within 14 days of the first day of study drug treatment.
• Use of erythroid stimulating agents, Granulocyte-colony stimulating factor (G-CSF), or Granulocyte-macrophage colony-stimulating factor (GM-CSF) within 14 days of the first day of study drug treatment, or during the study.
• Mean triplicate heart rate-corrected QT interval (QTc) > 500 msec.
• Any of the following cardiac abnormalities:
• QT interval > 480 msec corrected using Fridericia's formula;
• Risk factors for Torsade de Pointes;
• Use of medication that prolongs the QT interval with the exception of drugs that are considered absolutely essential for the care of the subject;
• Myocardial infarction ≤ 6 months prior to first day of study drug treatment;
• Unstable angina pectoris or serious uncontrolled cardiac arrhythmia.
• Any serious or uncontrolled medical disorder.
• Prior malignancy within the previous 2 years except for local cancers that have been cured; or patients who have been adequately treated and have low risk of reoccurrence.
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Use of other investigational drugs within 30 days of study drug administration.
• Major surgery within 4 weeks of study drug administration.
• Live-virus vaccination within 30 days of study drug administration.
• Allergy to study drug component.