A Phase 1, Study of BMF-500 in Adults With Acute Leukemia

Sponsor

Biomea Fusion Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05918692

Collaborator

(none)

110

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-500, an oral FLT3 inhibitor, in adult patients with acute leukemia.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Acute Mixed-Phenotype Leukemia	Drug: BMF-500	Phase 1

Detailed Description

A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-500, an oral covalent FLT3 inhibitor, in adult patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and Acute Mixed-Phenotype Leukemia (MPAL) who may or may not be on Antifungals.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Accelerated Titration Design, Followed by Modified 3+3Accelerated Titration Design, Followed by Modified 3+3

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Open-label, Dose-escalation, and Dose-expansion Study of BMF-500, an Oral Covalent FLT3 Inhibitor, in Adults With Acute Leukemia

Anticipated Study Start Date :

Jun 30, 2023

Anticipated Primary Completion Date :

Jul 31, 2025

Anticipated Study Completion Date :

Jul 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Escalation Phase BMF-500 taken twice daily by participants who are not receiving drugs that inhibit CYP3A4 activity or who are receiving necessary azole antifungals that are moderate or strong CYP3A4 inhibitors excluding other moderate or strong CYP3A4 inhibitors.	Drug: BMF-500 Investigational Product
Experimental: Expansion Phase BMF-500 taken twice daily by participants who are not receiving drugs that inhibit CYP3A4 activity or who are receiving necessary azole antifungals that are moderate or strong CYP3A4 inhibitors excluding other moderate or strong CYP3A4 inhibitors.	Drug: BMF-500 Investigational Product

Arm

Intervention/Treatment

Experimental: Escalation Phase

BMF-500 taken twice daily by participants who are not receiving drugs that inhibit CYP3A4 activity or who are receiving necessary azole antifungals that are moderate or strong CYP3A4 inhibitors excluding other moderate or strong CYP3A4 inhibitors.

Drug: BMF-500

Investigational Product

Experimental: Expansion Phase

Drug: BMF-500

Investigational Product

Outcome Measures

Primary Outcome Measures

Evaluate the safety and tolerability of BMF-500 monotherapy by incidence of Treatment Emerging Adverse Events (TEAEs). [At the end of each 28 Day cycle for a maximum of 32 cycles]
Assessed by the NCI CTCAE version 5.0.
Evaluate the safety and tolerability of BMF-500 monotherapy by incidence of Serious Adverse Events (SAEs). [At the end of each 28 Day cycle for a maximum of 32 cycles]
Assessed by the NCI CTCAE version 5.0.
Determine the recommended Phase 2 Dose (RP2D) of BMF-500. [At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period]
Safety, as determined by Dose-Limiting Toxicities (clinically significant Adverse Event) within each dose level assessed NCI CTCAE version 5.0.
Determine the recommended Phase 2 Dose (RP2D) of BMF-500. [At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period]
Efficacy within each dose level as determined by composite complete remission (CRc).
Determine the recommended Phase 2 Dose (RP2D) of BMF-500. [At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period]
Pharmacovigilance (PK) at each dose level as determined by the maximum plasma concentration (Cmax).
Determine the recommended Phase 2 Dose (RP2D) of BMF-500. [At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period]
Pharmacovigilance (PK) at each dose level as determined by area under the plasma concentration from time 0 to last quantifiable concentration (AUClast).

Secondary Outcome Measures

Determine the pharmacokinetics of BMF-500. [At the end of each cycle (each cycle is 28 days in duration) for 7 cycles]
Maximum plasma concentration (Cmax).
Determine the pharmacokinetics of BMF-500. [At the end of each cycle (each cycle is 28 days in duration) for 7 cycles]
Area under the plasma concentration from time 0 to last quantifiable concentration (AUClast).
Assess the effect of food on the PK exposure of BMF-500 in participants receiving BMF-500 (for escalation only). [At the end of cycle 1 and 2 (each cycle is 28 days in duration)]
Maximum plasma concentration (Cmax).
Assess the effect of food on the PK exposure of BMF-500 in participants receiving BMF-500 (for escalation only). [At the end of cycle 1 and 2 (each cycle is 28 days in duration)]
Area under the plasma concentration from time 0 to last quantifiable concentration (AUClast).
Evaluate the efficacy of BMF-500 [At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles]
Composite Complete Remission (CRc).
Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria. [At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles]
Duration of Response (DOR).
Evaluate the efficacy of BMF-500 [At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles]
Overall Reasons Rate (ORR).
Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria. [At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles]
Relapse free survival (RFS).
Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria. [At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles]
Overall Survival (OS).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Age ≥ 18 years.
Individuals with histologically or pathologically confirmed diagnosis of relapsed or refractory AML, ALL, or MPAL with documented FLT3 mutation, and/or Individuals with histologically or pathologically confirmed diagnosis of their malignancy with wild-type FLT3 (including those with MLL1-R and NPM1 mutations).
ECOG performance status of 0-2.
Adequate liver and renal function
Adhere to the CYP3A4 inhibitor concomitant therapy use requirements, as follows:
Arm A: Participants must not have received a moderate or strong CYP3A4 inhibitor for at least 7 days prior to enrollment and are not anticipated to require such agents in the near term (for at least 4 weeks).
Arm B: Participants must have received a necessary azole antifungal(s) that is a moderate or strong CYP3A4 inhibitor (excluding other moderate or strong CYP3A4 inhibitor[s]) for at least 7 days prior to enrollment and be able to continue such azole antifungal(s) while on BMF-500 treatment for at least 4 weeks.

Key Exclusion Criteria:

Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within 6 months prior to the first dose of the trial intervention.
WBC count >50,000/µL (uncontrollable with cytoreductive therapy).
Women who are pregnant or lactating or plan to become pregnant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Department of Medicine	Los Angeles	California	United States	90095
2	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
3	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
4	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
5	John Theurer Cancer Center	Hackensack	New Jersey	United States	07601
6	Roswell Park Comprehensive Cancer Center	Buffalo	New York	United States	14203
7	East Carolina University	Greenville	North Carolina	United States	27858
8	Cleveland Clinic Hospital	Cleveland	Ohio	United States	44195
9	Vanderbilt University Medical Center	Nashville	Tennessee	United States	77030
10	MD Anderson Cancer Center	Houston	Texas	United States	77030