Study of BMF-219, in Adult Patients With Acute Leukemia, Diffuse Large B-Cell Lymphoma and Multiple Myeloma

Sponsor

Biomea Fusion Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05153330

Collaborator

(none)

100

Enrollment

Locations

Arms

16.9

Anticipated Duration (Months)

14.3

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase1 first-in-human dose-escalation and dose-expansion study of BMF-219, an oral irreversible menin inhibitor, in adult patients with acute leukemia, diffuse large B-cell lymphoma, and multiple myeloma

Condition or Disease	Intervention/Treatment	Phase
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	Drug: BMF-219	Phase 1

Detailed Description

A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF 219, an oral irreversible menin inhibitor, in adult patients with acute leukemia (AL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM)

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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) and Cohort 3 (multiple myeloma) 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.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) and Cohort 3 (multiple myeloma) 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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

COVALENT-101: A Phase1 First-in-human Dose-escalation and Dose-expansion Study of BMF-219, an Oral Irreversible Menin Inhibitor, in Adult Patients With Acute Leukemia (AL), Diffuse Large B-cell Lymphoma (DLBCL), and Multiple Myeloma (MM)

Actual Study Start Date :

Jan 24, 2022

Anticipated Primary Completion Date :

Mar 20, 2023

Anticipated Study Completion Date :

Jun 21, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation Phase 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 Participants will receive 100 mg BMF-219 orally once per day to identify the OBD/RP2D (Optimal Biologic Dose/Recommended Ph2 Dose) Dose Expansion Phase: Cohorts 1, 2, and 3 will receive BMF-219 at the OPD/RP2D to further assess the safety/efficacy of the investigational drug.	Drug: BMF-219 BMF-219 is orally administered once daily in continuous 28 day cycles. Other Names: Irreversible Menin Inhibitor
Experimental: Dose Expansion 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 25 mg BMF-219 orally once per day 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 BMF-219 is orally administered once daily in continuous 28 day cycles. Other Names: Irreversible Menin Inhibitor

Arm

Intervention/Treatment

Experimental: Dose Escalation Phase

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 Participants will receive 100 mg BMF-219 orally once per day to identify the OBD/RP2D (Optimal Biologic Dose/Recommended Ph2 Dose) Dose Expansion Phase: Cohorts 1, 2, and 3 will receive BMF-219 at the OPD/RP2D to further assess the safety/efficacy of the investigational drug.

Drug: BMF-219

BMF-219 is orally administered once daily in continuous 28 day cycles.

Other Names:

Irreversible Menin Inhibitor

Experimental: Dose Expansion

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 25 mg BMF-219 orally once per day 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

BMF-219 is orally administered once daily in continuous 28 day cycles.

Other Names:

Irreversible Menin Inhibitor

Outcome Measures

Primary Outcome Measures

Determine Optimal Biologic Dose (OBD) and RP2D of BMF-219 monotherapy for (Cohorts 1, 2 and 3) [28 days]
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), and multiple myeloma (Cohort 3)

Secondary Outcome Measures

Evaluate the Safety by treatment-emergent TEAEs and SAEs [32 cycles]
Evaluate the Safety by treatment-emergent TEAEs and SAEs Evaluate safety of BMF-219 as expressed by treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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:

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 based on IMWG (International Myeloma Working Group) guidelines

Patients 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 but no more than 5 previous systemic regimens for the treatment of their de novo or transformed DLBCL (i.e., transformed from a previously diagnosed indolent lymphoma [e.g., follicular lymphoma])
Cohort 3 only: Must have received at least 3 but no more than 6 prior anti-MM regimens including proteasome inhibitor (e.g., bortezomib or carfilzomib) and immunomodulatory drug (IMiD) (e.g., lenalidomide or pomalidomide) therapy.

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:

Cohort 1: acute promyelocytic leukemia (APL), chronic myeloid leukemia (CML) in blast crisis, isolated extramedullary relapse (iEMR).
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

White Blood Count (WBC) > 50,000/μL (uncontrollable with cytoreductive therapy)
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

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 (e.g., cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to acute leukemia, DLBCL, or MM)
An active uncontrolled acute or chronic systemic fungal, bacterial, or viral infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Department of Medicine	Los Angeles	California	United States	90095
2	Mayo Clinic	Jacksonville	Florida	United States	32224
3	Moffitt Cancer Center	Tampa	Florida	United States	33612
4	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45219
5	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
6	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
7	MD Anderson Cancer Center	Houston	Texas	United States	77030