Sonrotoclax Plus Azacitidine in Patients With MDS-IB2

Prior treatment

• Prior treatment with chemotherapy, sonrotoclax, or other BCL-2 inhibitors.
• Active graft-versus-host disease (GVHD) after prior allogeneic hematopoietic stem cell transplantation or ongoing requirement for systemic immunosuppressive therapy.
• Anticipated need for continuous use of a strong CYP3A inhibitor during sonrotoclax initiation and dose ramp-up that cannot be discontinued or replaced.
• Concurrent participation in another interventional clinical study without meeting applicable discontinuation requirements.

Other illness

• Disease already transformed to acute myeloid leukemia (AML).
• Uncontrolled active infection, including severe bacterial, fungal, or viral infection.
• Active hepatitis B, hepatitis C, human immunodeficiency virus (HIV) infection, or active tuberculosis that is not adequately controlled.
• Significant uncontrolled cardiac, hepatic, renal, or other major organ dysfunction that, in the investigator's judgment, would preclude safe study treatment.
• Uncontrolled high risk of tumor lysis syndrome (TLS) that, in the investigator's judgment, makes the participant unsuitable for sonrotoclax treatment.
• Known severe hypersensitivity to sonrotoclax, azacitidine, or any of their excipients.
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in the study.

Other

• Pregnant or breastfeeding women.

• Age 18 to 70 years, male or female.
• Voluntarily willing to participate in the study, able to understand and sign written informed consent, and willing to comply with study treatment, assessments, and follow-up.
• Newly diagnosed with myelodysplastic syndromes with increased blasts-2 (MDS-IB2) according to the current World Health Organization (WHO) diagnostic criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Estimated life expectancy of at least 12 weeks.
• Adequate organ function to tolerate study treatment, including:
  • Total bilirubin ≤1.5 × upper limit of normal (ULN);
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN;
  • Creatinine clearance ≥40 mL/min;
  • Left ventricular ejection fraction (LVEF) ≥50%;
  • Baseline oxygen saturation \>92%.
• Able to take oral medication and without gastrointestinal disorders that would significantly affect drug absorption.
• Considered by the investigator to be able to safely receive sonrotoclax initiation and dose ramp-up.
• Participants of childbearing potential must have a negative pregnancy test and agree to use effective contraception during the study and for the protocol-specified period after the last dose of study treatment.