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

Phase 1

Active, not recruiting

• Conditions: Lymphoma; Myeloma, Plasma-Cell; Small Lymphocytic Lymphoma; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelomatosis; Plasma Cell Myeloma; Chronic Lymphocytic Leukemia; Acute Mixed-Phenotype Leukemia; Cancer
• Interventions: Drug: BMF-219

• Registration Number: NCT05153330
• Lead Sponsor: Biomea Fusion Inc.

Brief Summary

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.

Detailed 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).

Study Timeline

• Study First Submitted: 2021-11-30
• Study First Submitted QC: 2021-11-30
• Study First Posted: 2021-12-10
• Study Start: 2022-01-24
• Status Verified: 2025-02
• Primary Completion: 2025-02
• Last Update Submitted: 2025-02-14
• Last Update Posted: 2025-02-18
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 55

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose Escalation Phase	BMF-219	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.
Dose Expansion	BMF-219	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.

Primary Outcome Measures

Name	Time	Method
Determine Optimal Biologic Dose (OBD) and RP2D of BMF-219 monotherapy for (Cohorts 1, 2, 3 & 4)	At the end of Cycle 1 (each Cycle is 28 Days in duration)	Determine Optimal Biologic Dose (OBD) and recommended Phase 2 dose (RP2D) of BMF-219 monotherapy in subjects with refractory or relapsed (R/ R) acute leukemia (Cohort 1), diffuse large B-cell lymphoma (Cohort 2), multiple myeloma (Cohort 3), and chronic lymphocytic leukemia/ small lymphocytic lymphoma (Cohort 4).

Secondary Outcome Measures

Name	Time	Method
Evaluate the Safety treatment-emergent TEAEs and SAEs	At the end of Cycle 1 (each Cycle is 28 Days in duration)	Evaluate the Safety of BMF-219 as expressed by treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).

Trial Locations

Locations (41)

University of California, Irvine; 🇺🇸 Irvine, California, United States

University of Southern California Norris Cancer Center; 🇺🇸 Los Angeles, California, United States

UCLA Department of Medicine; 🇺🇸 Los Angeles, California, United States

UC Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

Stanford Cancer Center; 🇺🇸 Stanford, California, United States

Mayo Clinic; 🇺🇸 Jacksonville, Florida, United States

Mount Sinai Medical Center; 🇺🇸 Miami Beach, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Blood & Marrow Transplant Group of GA (Northside Hospital); 🇺🇸 Atlanta, Georgia, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

University of Cincinnati Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Virginia Cancer Specialists; 🇺🇸 Gainesville, Virginia, United States

Evangelismos General Hospital of Athens; 🇬🇷 Athens, Greece

Alexandra General Hospital of Athens; 🇬🇷 Athens, Greece

AOU Ospedali Riuniti Ancona; 🇮🇹 Ancona, Italy

ASST Papa Giovanni XXIII Hospital Bergamo; 🇮🇹 Bergamo, Italy

Istituto Europeo di Oncologia; 🇮🇹 Milano, Italy

Instituto Clinico Humanitas; 🇮🇹 Milan, Italy

IRCCS Ospedale San Raffaele, Programma di Ricerca Strategica su LLC; 🇮🇹 Milan, Italy

Ospedale Santa Maria della Misericordia; 🇮🇹 Perugia, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Roma, Italy

Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands

UMCG Groningen; 🇳🇱 Groningen, Netherlands

Radboud University Medical Center; 🇳🇱 Nijmegen, Netherlands

Erasmus University Medical Center Rotterdam; 🇳🇱 Rotterdam, Netherlands

Hospital General de Albacete; 🇪🇸 Albacete, Spain

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Institut Catala d'Oncologia; 🇪🇸 Barcelona, Spain

Hospital San Pedro de Alcántara; 🇪🇸 Cáceres, Spain

Hospital Universitario de la Princesa; 🇪🇸 Madrid, Spain

Hospital Universitario Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario Central de Asturias; 🇪🇸 Oviedo, Spain

Hospital Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

Hospital Universitario y Politécnico La Fe; 🇪🇸 Valencia, Spain