A Phase 1, Open-Label, Dose-Escalation with Expansion Study of SX-682 Alone and in Combination with Oral or Intravenous Decitabine in Subjects with Myelodysplastic Syndrome
This study will determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and recommended Phase 2 dose (RP2D) of SX-682 in the treatment of patients with Myelodysplastic Syndromes (MDS).
• 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.