Safety and Efficacy of RVU120 for Treatment of Relapsed/Refractory AML

Prior treatment

• Previous treatment with CDK8 and/or CDK19-targeted therapy.
• Major surgery within 28 days prior to first dose of study drug.
• Hematopoietic stem cell transplant within 120 days prior to first dose of study drug.
• Concurrent participation in another investigational clinical trial.
• Taking any medications, herbal supplements, or other substances (including smoking) that may interfere with the metabolism of the study drug

Other illness

• Active, ≥Grade 2 acute graft versus host disease (GVHD), active moderate-to-severe chronic GVHD, or requirement for systemic immunosuppressive medications for GVHD
• Evidence of ongoing and uncontrolled systemic bacterial, fungal, or viral infection and acute inflammatory conditions (including pancreatitis).
• Known seropositivity or history of active viral infection with human immunodeficiency virus (HIV).
• Ongoing significant liver disease
• Impairment of gastrointestinal function or gastrointestinal disease
• Ongoing drug-induced pneumonitis.
• Prior history of malignancies other than AML, unless the participant has been free of the disease for 5 years or more prior to Screening

Lab values

• Significant cardiac dysfunction defined as myocardial infarction within 12 months of first dose of study drug, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled dysrhythmias, poorly controlled angina or left ventricular ejection fraction (LVEF) <40% as per echocardiography or multiple gated acquisition (MUGA) scan.
• History of ventricular arrhythmia, or QTc ≥470 ms (Bazett's formula).

Other

• Active central nervous system (CNS) leukemia.
• Diagnosis of acute promyelocytic leukemia (APL), the M3 subtype of AML.
• Pregnant or breast-feeding.

• Subjects must sign a written informed consent document and complete study related procedures
• Patients must have a diagnosis of AML or HR-MDS (per 2022 WHO classification) with MDS confirmed as high risk with IPSS-R
• Patients must have relapsed or refractory AML (per ELN 2022 criteria)
• Patients must have relapsed or progressing HR-MDS (per IWG response criteria)
• Patients must have failed first-line treatment and have no alternative therapeutic options likely to produce clinical benefit
• Patients must have ECOG performance status of 0 to 2
• Patients must have adequate end organ function defined as:
  • WBC < 30 x 10(9)/L on Day 1 prior to first dose of study drug
  • Platelet count > 10,000/mcL on Day 1 prior to first dose of study drug
  • Serum albumin ≥ 25 g/L (2.5 g/dL)
  • Normal coagulation (elevated international normalized ratio [INR], prothrombin time or activated partial thromboplastin time [APTT] <1.3 x the upper limit of normal [ULN] acceptable)
  • AST (aspartate transaminase) and ALT (alanine transaminase) ≤ 3 x ULN (upper limit of normal)
  • Total bilirubin ≤ 3 x ULN
  • Creatinine clearance (Cockcroft \& Gault formula) ≥ 30 mL/min