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

NCT05153330 | Terminated Phase 1 FDA Drug

• 1 other identifier: COVALENT-101
• Study Type: interventional
• Target: 55
• Locations: 5 countries
• Sites: 41

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Determine Optimal Biologic Dose (OBD) and RP2D of BMF-219 monotherapy for (Cohorts 1, 2, 3 & 4)

  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).

  At the end of Cycle 1 (each Cycle is 28 Days in duration)

Secondary Outcomes (1)

• Evaluate the Safety treatment-emergent TEAEs and SAEs

  28 Days after last dose.

Study Arms (2)

Dose Escalation Phase

EXPERIMENTAL

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.

Drug: BMF-219

Dose Expansion

EXPERIMENTAL

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.

Drug: BMF-219

Interventions

BMF-219 DRUG

BMF-219 is orally administered in continuous 28 day cycles. Alternative BID dosage may be used.

Also known as: Covalent Menin Inhibitor

Dose Escalation Phase; Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• All subjects must have histologically or pathologically confirmed diagnosis of their malignancy and/ or measurable R/ R disease, as follows:
• Cohort 1 only: Refractory or relapsed acute leukemia defined as \> 5% blasts in the bone marrow or reappearance of blasts in the peripheral blood.
• 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.
• Cohort 3 only: Measurable MM.
• 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:
• Cohort 1 only: Have failed or are ineligible for any approved standard of care therapies, including HSCT (Hematopoietic Stem Cell Transplantation).
• Cohort 2 only: Must have received at least 2 previous systemic regimens for the treatment of their de novo or transformed DLBCL.
• Cohort 3 only: Must have received at least 3 anti-MM regimens including proteasome inhibitor.
• 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.

You may not qualify if:

• 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:
• Cohort 1: Acute promyelocytic leukemia (APL), chronic myeloid leukemia (CML) in blast crisis.
• Cohort 2: Primary mediastinal B-cell lymphoma (PMBCL), DLBCL transformed from diseases other than indolent non-Hodgkin's Lymphoma (NHL).
• Cohort 3: Active plasma cell leukemia, myeloma with amyloidosis, systemic light chain amyloidosis.
• 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:
• Cohort 1: Clinically active central nervous system (CNS) leukemia. Previously controlled CNS leukemia is acceptable.
• Cohort 2: Active CNS lymphoma or meningeal involvement.
• Cohort 3: Active CNS MM.
• 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.

Sponsors & Collaborators

• Biomea Fusion Inc.: lead

Study Sites (41)

University of California, Irvine

Irvine, California, 92697, United States

Location

University of Southern California Norris Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA Department of Medicine

Los Angeles, California, 90095, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Blood & Marrow Transplant Group of GA (Northside Hospital)

Atlanta, Georgia, 30342, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists

Gainesville, Virginia, 20155, United States

Location

Evangelismos General Hospital of Athens

Athens, 106 76, Greece

Location

Alexandra General Hospital of Athens

Athens, 115 28, Greece

Location

AOU Ospedali Riuniti Ancona

Ancona, 60126, Italy

Location

ASST Papa Giovanni XXIII Hospital Bergamo

Bergamo, 24128, Italy

Location

Instituto Clinico Humanitas

Milan, 20089, Italy

Location

IRCCS Ospedale San Raffaele, Programma di Ricerca Strategica su LLC

Milan, 20132, Italy

Location

Istituto Europeo di Oncologia

Milan, 435 - 20141, Italy

Location

Ospedale Santa Maria della Misericordia

Perugia, 06132, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

Amsterdam UMC

Amsterdam, 1081HV, Netherlands

Location

UMCG Groningen

Groningen, 9700 RB, Netherlands

Location

Radboud University Medical Center

Nijmegen, 6500 HB, Netherlands

Location

Erasmus University Medical Center Rotterdam

Rotterdam, 3015 GD, Netherlands

Location

Hospital General de Albacete

Albacete, 02006, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Institut Catala d'Oncologia

Barcelona, 08916, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, 10003, Spain

Location

Hospital Universitario de la Princesa

Madrid, 28006, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasms; Disease Progression; Lymphoma, Large B-Cell, Diffuse; Multiple Myeloma; Lymphoma; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, B-Cell; Chronic Disease

Study Officials

• Steve Morris, MD

  Biomea Fusion Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The first-in-human (FIH) study is a dose-escalation/dose-expansion study of BMF-219. During the dose-escalation phase of the study, the optimal biologic dose (OBD) and recommended Phase 2 dose (RP2D) of BMF-219 will be determined. Subjects in Cohort 1 (acute leukemia) are assigned to one of two parallel arms; ARM A (subjects not receiving CYP3A4 inhibitors) and ARM B (subjects receiving CYP3A4 inhibitors); Subjects in Cohort 2 (DLBCL), Cohort 3 (multiple myeloma), and Cohort 4 (chronic lymphocytic leukemia/ small lymphocytic lymphoma) are assigned to a single arm (ARM A).The dose-expansion phase will obtain further safety, as well as efficacy data for BMF-219 when dosed at the OBD and RP2D.

Study Record Dates

• First Submitted: November 30, 2021
• First Posted: December 10, 2021
• Study Start: January 24, 2022
• Primary Completion: February 13, 2025
• Study Completion: May 2, 2025
• Last Updated: July 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (17); GR (2); NL (4); ES (11); IT (7)