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

Cancer Clinical Trial

Official title:

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 Leukemia (AL), Diffuse Large B-cell Lymphoma (DLBCL), Multiple Myeloma (MM), and Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05153330
• Other study ID #: COVALENT-101
• Status: Recruiting
• Phase: Phase 1
• Start date: January 24, 2022
• Est. completion date: March 31, 2025

Study information

• Verified date: March 2024
• Source: Biomea Fusion Inc.
• Contact: Mona Vimal
• Phone: 1-844-245-0490
• Email: clinicaltrials[@]biomeafusion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 177
• Est. completion date: March 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Cancer
• Chronic Lymphocytic Leukemia
• Diffuse Large B Cell Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Myeloma, Plasma-Cell
• Myelomatosis
• Neoplasms, Plasma Cell
• Plasma Cell Myeloma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Progression
• Refractory
• Small Lymphocytic Lymphoma

Intervention

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

Locations

Country	Name	City	State
Greece	Alexandra General Hospital of Athens	Athens
Greece	Evangelismos General Hospital of Athens	Athens
Italy	AOU Ospedali Riuniti Ancona	Ancona
Italy	ASST Papa Giovanni XXIII Hospital Bergamo	Bergamo
Italy	Instituto Clinico Humanitas	Milan
Italy	IRCCS Ospedale San Raffaele, Programma di Ricerca Strategica su LLC	Milan
Italy	Istituto Europeo di Oncologia	Milano
Italy	Ospedale Santa Maria della Misericordia	Perugia
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Netherlands	Amsterdam UMC	Amsterdam
Netherlands	UMCG Groningen	Groningen
Netherlands	Radboud University Medical Center	Nijmegen
Netherlands	Erasmus University Medical Center Rotterdam	Rotterdam
Spain	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 12 de Octubre	Madrid
Spain	Hospital Universitario de la Princesa	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	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
United States	Blood & Marrow Transplant Group of GA (Northside Hospital)	Atlanta	Georgia
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Virginia Cancer Specialists	Gainesville	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of California, Irvine	Irvine	California
United States	Mayo Clinic	Jacksonville	Florida
United States	UCLA Department of Medicine	Los Angeles	California
United States	University of Southern California Norris Cancer Center	Los Angeles	California
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Stanford Cancer Center	Stanford	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Biomea Fusion Inc.

Countries where clinical trial is conducted

United States,  Greece,  Italy,  Netherlands,  Spain, 

Outcome

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