BY002 IIT Study in R/R Acute Leukemia

Prior treatment

• Active central nervous system (CNS) leukemia. (Prior CNS involvement allowed if treated and controlled; CNS prophylaxis permitted.)
• Autologous HSCT or CAR-T therapy within 60 days, or unresolved toxicities from ASCT/CAR-T.
• Allogeneic HSCT within 100 days, or active GVHD, or requiring ongoing immunosuppressive therapy.
• Anti-leukemia therapy within 2 weeks before study entry (hydroxyurea permitted).
• Prior investigational drug use: \<2 weeks or \<5 half-lives for small molecules; \<4 weeks or \<5 half-lives for biologics (whichever is shorter).
• Unresolved toxicities \> grade 1 from prior anti-leukemia therapy (except alopecia).

Other illness

• History of significant liver disease, including viral hepatitis or cirrhosis:
• HBsAg positive must have negative HBV DNA.
• HCV antibody positive must have negative HCV RNA.
• Known HIV infection.
• Significant cardiac disease:
• Acute myocardial infarction, unstable angina, or coronary artery bypass within 6 months.
• Congestive heart failure ≥ NYHA class II.
• History of another malignancy within 5 years, except adequately treated basal cell carcinoma of the skin, in-situ breast cancer, or in-situ cervical cancer.
• Uncontrolled active infection:
• Mild infections manageable with oral/topical treatment are allowed.
• Serious infections requiring hospitalization/IV antibiotics within 14 days excluded, unless resolved.
• Febrile neutropenia without infection evidence may be eligible if afebrile \>72 h without antipyretics.
• Active tuberculosis excluded.
• Conditions impairing oral intake or absorption (e.g., swallowing difficulty, short bowel syndrome, gastroparesis).
• Known severe allergy to Menin inhibitors or any component of BY002.
• Any other serious disease, abnormality, or condition that may increase risk, interfere with study drug, confound results, or expected survival ≤6 months.

Lab values

• Congenital long QT syndrome or QTcF \>450 msec.

Other

• Pregnant or breastfeeding women.
• Investigator judges poor compliance or inability to complete study.

• Age ≥16 years.
• Confirmed diagnosis of AML, ALL, or MPAL per WHO 2022 criteria.
• Relapsed or refractory disease after ≥1 prior therapy.
• Presence of KMT2A rearrangement or NPM1 mutation (preferred, but not exclusive).
• ECOG performance status 0-2.
• Adequate organ function:
• ANC ≥1.0 × 10⁹/L (unless cytopenia due to leukemia)
• Platelets ≥50 × 10⁹/L (unless due to leukemia)
• ALT/AST ≤2.5 × ULN, bilirubin ≤1.5 × ULN
• Creatinine clearance ≥50 mL/min
• Negative pregnancy test for women of childbearing potential.
• Willing to use effective contraception during study and 90 days after last dose.
• Signed informed consent.