BY002 for relapsed or refractory acute leukemia with KMT2A rearrangements or NPM1 mutations

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 trial tests an oral menin inhibitor, BY002, in adults with relapsed or refractory AML, ALL, or MPAL who have KMT2A rearrangements or NPM1 mutations to see if it is safe and shows early signs of benefit.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 16 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (other)
• Drugs / interventions: CAR-T
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07270770 on ClinicalTrials.gov

What this trial studies

This single-center, open-label phase 1 trial uses a 3+3 dose-escalation design with an expansion cohort to define the recommended phase 2 dose of BY002. Eligible adults with relapsed or refractory AML, ALL, or MPAL (excluding APL) who harbor KMT2A rearrangements or NPM1 mutations will receive oral BY002 in 28-day cycles until disease progression, unacceptable toxicity, hematopoietic stem cell transplant, withdrawal, or death. Primary endpoints are dose-limiting toxicities, serious adverse events, and determination of the maximum tolerated dose and RP2D, and secondary endpoints include pharmacokinetics, comprehensive safety monitoring, and preliminary anti-leukemia activity. Safety evaluations include adverse event reporting, laboratory tests, vital signs, and ECGs performed at scheduled visits.

Who should consider this trial

Good fit: Adults (≥16 years) with relapsed or refractory AML, ALL, or MPAL (not APL) who carry KMT2A rearrangements or NPM1 mutations, have ECOG 0–2, adequate organ function, and no better treatment options are ideal candidates.

Not a fit: Patients without KMT2A rearrangements or NPM1 mutations, those with active uncontrolled CNS leukemia, significant liver disease, inadequate organ function, or who have better standard treatment options or immediate transplant plans are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, BY002 could offer a targeted oral therapy that overcomes resistance and induces remissions in patients with KMT2A-rearranged or NPM1-mutant relapsed/refractory acute leukemia.

How similar studies have performed: Other menin inhibitors have shown promising responses in early-phase trials for KMT2A- or NPM1-mutant leukemias, so the approach has supportive early clinical data, although BY002 itself is a newer agent.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (RECRUITING)

Study contacts

• Principal investigator: Suning Chen, MD, PhD — The First Affiliated Hospital of Soochow University
• Study coordinator: Jing Lu Doctor, MD, PhD

Conditions: Acute Leukemia, KMT2A Rearrangements or NPM1 Mutations Acute Leukemia, KMT2A rearrangements or NPM1 mutations, relapsed or refractory acute leukemia, Menin Inhibitor