Treatment of Acute Leukemia with BN104

A PhaseI/II, Multicenter, Open-label Clinical Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of the Menin Inhibitor BN104 in the Treatment of Patients With Relapsed/Refractory Acute Leukemia

This study is testing a new treatment called BN104 to see if it can help people with relapsed or hard-to-treat acute leukemia feel better and improve their outcomes.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: BioNova Pharmaceuticals (Shanghai) LTD. (industry)
• Drugs / interventions: CAR T, CAR-T, chimeric antigen receptor, chemotherapy, immunotherapy
• Locations: 1 site (Suzhou)
• Trial ID: NCT06052813 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety, pharmacokinetics, and preliminary efficacy of BN104, administered once or twice daily, in patients with relapsed or refractory acute leukemia, including acute lymphocytic leukemia (ALL) and acute myeloblastic leukemia (AML). The study is divided into two phases: Phase I focuses on dose escalation to determine the maximum tolerated dose, while Phase II aims to further assess safety and efficacy in specific genetic subgroups of acute leukemia. Patients will be monitored through regular laboratory tests and efficacy assessments throughout the treatment cycles.

Who should consider this trial

Good fit: Ideal candidates include adults with relapsed or refractory acute leukemia who have specific genetic mutations and for whom no superior treatment options are available.

Not a fit: Patients with acute promyelocytic leukemia or those who have not exhausted other treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat acute leukemia.

How similar studies have performed: Other studies have shown promise in targeting specific mutations in acute leukemia, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. Have been fully informed about the study and have voluntarily signed the ICF;
2. patients with relapsed/refractory acute leukemia (including AML, ALL, and mixed-spectrum leukemias, except acute promyelocytic leukemia) diagnosed according to the 2022 World Health Organization (WHO) criteria, and for whom there are no superior therapeutic alternatives as assessed by the investigator, and who meet at least one of the following criteria:

   * Primary refractory disease;
   * First relapse with duration of first remission ≤ 12 months
   * Relapsed/refractory disease after 2 or more lines of therapy;
   * Relapse after allogeneic hematopoietic stem cell transplantation (patients who relapse after autologous hematopoietic stem cell transplantation and immune cell therapy \[including, but not limited to, chimeric antigen receptor T-cells\] may also be enrolled if there is no superior therapeutic regimen in the investigator's assessment);

   Notes:
   * Secondary AML or AML transformed by myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) may also be enrolled;
   * Control of peripheral blood leukocyte counts with hydroxyurea is allowed prior to study drug administration and for 2 weeks after initiation of study drug administration.
3. For Phase I dose-optimization and Phase II subjects, the combination of NPM1 mutation or KMT2A rearrangement should also be specified.
4. Age ≥ 18 years;
5. ECOG score 0-2;
6. Adequate hepatic, renal, and cardiac functions
7. Expected survival of more than 12 weeks as judged by the investigator
8. Be able to perform treatments, visits, and undergo study-related testing as required by the protocol
9. Female patients of childbearing potential or male patients whose female partners are of childbearing potential must agree to use an effective method of contraception, such as a double-barrier method of contraception, condoms, oral or injectable contraceptives, and intrauterine devices (IUDs), for the duration of the study and for 30 days after the last study dose. Postmenopausal women (\>45 years of age and menopause for more than 1 year) and surgically sterilized women are not subject to this condition.

Exclusion Criteria:

1. definite active central nervous system (CNS) leukemia (previous CNS leukemia that has been treated and controlled, but requires screening period lumbar puncture for cerebrospinal fluid examination for confirmation, or routine receipt of standard CNS prophylaxis are acceptable);
2. a known history of clinically significant liver disease, including viral or other hepatitis or cirrhosis
3. known human immunodeficiency virus (HIV) infection;
4. pregnant (positive screening pregnancy test) or lactating females;
5. meet any of the following cardiac-related criteria:

   * Hereditary long QT interval syndrome or QTcF \> 450 msec;
   * Various clinically significant cardiovascular diseases, including acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting within 6 months prior to enrollment, congestive heart failure graded by the New York Heart Association (NYHA) as grade 2 or higher (inclusive);
6. the patient has suffered from other malignant tumors within the past 5 years, except for radically treated basal cell carcinoma of the skin, carcinoma in situ of the breast or carcinoma in situ of the cervix;
7. has received autologous hematopoietic stem cell transplantation (ASCT) or chimeric antigen receptor T cell (CAR T) therapy within 60 days prior to screening, or has not recovered from toxicity associated with ASCT or CAR-T therapy
8. allogeneic hematopoietic stem cell transplantation has been performed within 100 days prior to screening, or the patient is still comorbid with active acute or chronic graft-versus-host disease, or the patient is still in need of immunosuppressive therapy;
9. anti-leukemia therapy, including chemotherapy, radiotherapy, hormone therapy, or immunotherapy (excluding hydroxyurea) within 2 weeks prior to the start of study treatment;
10. prior participation in a clinical study of another drug less than 2 weeks or 5 half-lives for small molecules and less than 4 weeks or 5 half-lives for large molecules (e.g., antibody-based drugs) from the last dose, whichever is shorter
11. prior treatment with targeted menin;
12. prior toxic reactions to anti-leukemia therapy that have not returned to grade 0 or 1 levels (except alopecia areata)
13. uncontrolled active infection:

    * Patients with non-serious infectious complications (e.g., oral Candida infection or uncomplicated urinary tract infection) for which oral/topical anti-infective therapy is being applied may be enrolled;
    * Patients with severe infections requiring hospitalization or intravenous antibiotic therapy within 14 days prior to enrollment, patients with no evidence of infection, and patients receiving prophylactic anti-infective, antifungal, or antiviral therapy for prolonged neutropenia may be enrolled;
    * Patients treated with intravenous antibiotics or hospitalized for febrile neutropenia, but no evidence of infectious etiology has been found, and patients with normal body temperature for more than 72 hours without antipyretic medication may be enrolled;
14. subjects with known dysphagia, short bowel syndrome, gastroparesis, or other conditions that limit oral drug intake or gastrointestinal absorption;
15. a history of severe allergy to menin inhibitors or hypersensitivity to any of the components of BN104
16. inadequate patient compliance with participation in this clinical study as judged by the investigator;
17. any other disease, metabolic abnormality, physical examination abnormality, or clinically significant laboratory test abnormality that, in the judgment of the investigator, gives reason to suspect that the patient has a disease or condition that is inappropriate for the use of the study medication, or that will interfere with the interpretation of the results of the study, or that places the patient at high risk.

Where this trial is running

Suzhou

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

Study contacts

• Principal investigator: Depei WU, Prof. — The First Affiliated Hospital of Soochow University
• Study coordinator: Yolin Pan

Conditions: ALL, Adult, AML, Adult