Study of BMF-219, a Covalent Menin Inhibitor, in Adult Patients With AML, ALL (With KMT2A/ MLL1r, NPM1 Mutations), DLBCL, MM, and CLL/SLL

Biomea Fusion

Status and phase: Enrolling; Phase 1

Conditions: Myelomatosis; Acute Mixed-Phenotype Leukemia; Small Lymphocytic Lymphoma; Cancer; Lymphoma, Non-Hodgkin; Plasma Cell Myeloma; Multiple Myeloma; Refractory; Progression; Myeloma, Plasma-Cell; Lymphoma; Chronic Lymphocytic Leukemia; Acute Lymphoblastic Leukemia; Diffuse Large B Cell Lymphoma; Acute Myeloid Leukemia

Treatments: Drug: BMF-219

Study type: Interventional

Funder types: Industry

Identifiers

NCT05153330

COVALENT-101

Details and patient eligibility

About

A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-219, an oral covalent menin inhibitor, in adult patients with AML, ALL (with KMT2A/ MLL1r, NPM1 mutations), DLBCL, MM, and CLL/SLL.

Full description

A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-219, an oral covalent menin inhibitor, in adult patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) with mixed lineage leukemia 1-rearranged (KMT2A/ MLL1r), nucleophosmin 1 (NPM1), diffuse large b-cell lymphoma (DLBCL), multiple myeloma (MM), and chronic lymphocytic lymphoma (CLL)/ small lymphocytic lymphoma (SLL).

Enrollment: 177 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥ 18 years.

• All subjects must have histologically or pathologically confirmed diagnosis of their malignancy and/ or measurable R/ R disease, as follows:

  1. Cohort 1 only: Refractory or relapsed acute leukemia defined as > 5% blasts in the bone marrow or reappearance of blasts in the peripheral blood.
  2. Cohort 2 only: Previously treated, pathologically confirmed de novo DLBCL, or DLBCL transformed from previously indolent lymphoma (e.g., follicular lymphoma) with documented clinical or radiological evidence of progressive or persistent disease. At study entry, subjects must have measurable disease as per the revised criteria for response assessment of lymphoma.
  3. Cohort 3 only: Measurable MM.
  4. Cohort 4 only: Previously treated subjects with active CLL/SLL with meeting at least 1 of the iwCLL 2018 criteria for requiring treatment.

• Subjects must be refractory or must have progressed on, or following discontinuation of the most recent anti-cancer therapy, with the following considerations:

  1. Cohort 1 only: Have failed or are ineligible for any approved standard of care therapies, including HSCT (Hematopoietic Stem Cell Transplantation).
  2. Cohort 2 only: Must have received at least 2 previous systemic regimens for the treatment of their de novo or transformed DLBCL.
  3. Cohort 3 only: Must have received at least 3 anti-MM regimens including proteasome inhibitor.
  4. Cohort 4 only: Must have received at least 2 prior systemic treatment regimens.

• ECOG performance status of 0-2 and an estimated expected life expectancy of > 3 months in the opinion of the Investigator.

• Adequate organ function.

• Both men and women of childbearing potential or their partners must use adequate birth control measures during the course of the trial and for at least 90 days after discontinuing study treatment.

Exclusion criteria

Subjects who meet any of the following criteria will not be enrolled in the study (all cohorts, unless otherwise indicated):

• Certain disease subtypes or occurrences, as follows:

  1. Cohort 1: Acute promyelocytic leukemia (APL), chronic myeloid leukemia (CML) in blast crisis.
  2. Cohort 2: Primary mediastinal B-cell lymphoma (PMBCL), DLBCL transformed from diseases other than indolent non-Hodgkin's Lymphoma (NHL).
  3. Cohort 3: Active plasma cell leukemia, myeloma with amyloidosis, systemic light chain amyloidosis.
  4. Cohort 4: Known or suspected history of Richter's transformation.

• White Blood Count (WBC) > 50,000/μL (uncontrollable with cytoreductive therapy) (Cohort 1 only).

• Known central nervous involvement, as follows:

  1. Cohort 1: Clinically active central nervous system (CNS) leukemia. Previously controlled CNS leukemia is acceptable.
  2. Cohort 2: Active CNS lymphoma or meningeal involvement.
  3. Cohort 3: Active CNS MM.
  4. Cohort 4: Active CNS leukemia.

• Prior menin inhibitor therapy.

• Known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen.

• Subjects with a pre-existing disorder predisposing them to a serious or life-threatening infection.

• An active uncontrolled acute or chronic systemic fungal, bacterial, or viral infection.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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177 participants in 2 patient groups

Dose Escalation Phase

Experimental group

Description:

Experimental: ARM A: Study participants who are not receiving a moderate or strong CYP3A4 inhibitor. Dose Escalation Phase: * Cohort 1: Participants with acute leukemia * Cohort 2: Participants with diffuse large B-cell lymphoma * Cohort 3: Participants with multiple myeloma * Cohort 4: Participants with chronic lymphocytic leukemia/ small lymphocytic lymphoma Participants will receive escalating dose BMF-219 orally once per day to identify the OBD/RP2D (Optimal Biologic Dose/Recommended Ph2 Dose). Dose Expansion Phase: Cohorts 1, 2, 3, and 4 will receive BMF-219 at the OBD/ RP2D to further assess the safety/ efficacy of the investigational drug.

Treatment:

Drug: BMF-219

Dose Expansion

Experimental group

Description:

Experimental: ARM B: Study participants who are receiving a moderate or strong CYP3A4 inhibitor. Dose Escalation Phase: • Cohort 1: Participants with acute leukemia will receive escalating dose BMF-219 orally to identify the OBD/ RP2D (Optimal Biologic Dose/Recommended Ph2 Dose). Dose Expansion Phase: Cohort 1 will receive BMF-219 at the OBD/ RP2D to further assess the safety and efficacy of the investigational drug.

Treatment:

Drug: BMF-219