RecruitingPhase 1NCT07270770

BY002 IIT Study in R/R Acute Leukemia

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

Sponsor

The First Affiliated Hospital of Soochow University

Enrollment

18 participants

Start Date

Mar 15, 2026

Study Type

INTERVENTIONAL

Conditions

Acute Leukemia KMT2A Rearrangements or NPM1 Mutations Acute Leukemia

Summary

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) , 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.

Eligibility

Min Age: 16 Years

Inclusion Criteria13

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.

Exclusion Criteria25

Active central nervous system (CNS) leukemia. (Prior CNS involvement allowed if treated and controlled; CNS prophylaxis permitted.)
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.
Pregnant or breastfeeding women.
Significant cardiac disease:
Congenital long QT syndrome or QTcF \>450 msec.
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.
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).
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.
Investigator judges poor compliance or inability to complete study.
Any other serious disease, abnormality, or condition that may increase risk, interfere with study drug, confound results, or expected survival ≤6 months.

Interventions

DRUGBY002

BY002 capsule (oral) * Starting dose: 50 mg BID * Dose escalation: 100 mg BID → 150 mg BID → 200 mg BID (3+3 design) * Treatment cycle: 28 days, repeated until disease progression, unacceptable toxicity, HSCT, withdrawal, or death