A Single-center, Open-label, Investigator-Initiated Trial to Evaluate the Safety, Pharmacokinetics, and Efficacy of Menin Inhibitor BY002 in Patients With Relapsed or Refractory Acute Leukemia
This is a single-center, open-label, investigator-initiated phase 1 study designed to evaluate the safety, pharmacokinetics (PK), and preliminary efficacy of the menin inhibitor BY002 in patients with relapsed or refractory acute leukemia. Eligible subjects include adult patients (≥18 years) with AML, ALL, or MPAL, excluding APL, who carry KMT2A rearrangement or NPM1 mutation and have no better treatment options. The study will be conducted in a dose-escalation design (3+3) with an accelerated titration at the starting dose, followed by expansion at the recommended dose. BY002 is administered orally in 28-day cycles until disease progression, unacceptable toxicity, HSCT, withdrawal, or death. The primary objectives are to determine the incidence of dose-limiting toxicities (DLTs) and serious adverse events (SAEs), and to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Secondary objectives include characterization of PK parameters, evaluation of safety (AEs, laboratory tests, vital signs, ECG), and assessment of efficacy endpoints such as complete remission (CR), composite remission (CRc), overall response rate (ORR), duration of response (DOR), event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), and cumulative incidence of relapse (CIR). Exploratory objectives include analysis of pharmacodynamic biomarkers (e.g., HOXA9, MEIS1, CD11b) and correlation of baseline genetic mutations (e.g., NPM1, KMT2A, FLT3, TP53, NUP98) with clinical outcomes.
• Age ≥18 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.