BY002 IIT Study in R/R Acute Leukemia

NCT07270770 | Recruiting Phase 1 DMC

• 1 other identifier: 2nd_Menin inhibitor
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Leukemia; KMT2A Rearrangements or NPM1 Mutations Acute Leukemia

Keywords

KMT2A rearrangements or NPM1 mutations; relapsed or refractory acute leukemia; Menin Inhibitor

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLT)

  A DLT is defined as any ≥Grade 3 non-hematologic or ≥Grade 4 hematologic toxicity considered related to BY002, occurring during the DLT evaluation period. The number and proportion of participants with DLTs will be summarized.

  From Cycle 1 Day 1 (C1D1) through the end of the DLT observation period (Day 1-28; may extend to Day 42 if toxicity evaluation is delayed).

• Incidence of serious adverse events (SAEs)

  SAEs will be defined and classified according to ICH E2A and CTCAE v5.0. The number and proportion of participants experiencing ≥1 SAE will be summarized.

  From Cycle 1 Day 1 (C1D1) until 30 days after the last dose.

Secondary Outcomes (3)

• Incidence, type, and severity of all adverse events (AEs)

  From first dose until 30 days after the last dose.

• Plasma concentrations of BY002 and its primary metabolite (M1)

  Cycle 0 Day 1 (single-dose PK) and throughout treatment cycles, up to 30 days after the last dose.

• Proportion of participants achieving complete remission (CR/CRi) per ELN 2022 criteria

  From first dose until disease progression, relapse, or death, assessed up to approximately 24 months.

Other Outcomes (1)

• Pharmacodynamic biomarker changes and correlation of baseline genomic mutations with clinical efficacy

  From baseline until end of study (up to 24 months).

Study Arms (1)

BY002 treatment

EXPERIMENTAL

BY002 capsule (oral) * 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

Drug: BY002

Interventions

BY002 DRUG

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

BY002 treatment

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215000, China

RECRUITING

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Suning Chen, MD, PhD

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jing Lu Doctor, MD, PhD

CONTACT

86+0512-67781137; gloriajlu@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: October 2, 2025
• First Posted: December 8, 2025
• Study Start: March 15, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

CN (1)