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

NCT05918692 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: COVALENT-103
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 14

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.

Conditions

Acute Myeloid Leukemia

Keywords

FLT3; FLT3-ITD; FLT-TKD; AML; FLT3 Wild-Type; MLL-R; NPM1; CYP3A4

Outcome Measures

Primary Outcomes (6)

• Evaluate the safety and tolerability of BMF-500 by incidence of Treatment Emergent Adverse Events (TEAEs).

  Assessed by the NCI CTCAE version 5.0.

  At the end of each 28 Day cycle for a maximum of 32 cycles

• Evaluate the safety and tolerability of BMF-500 by incidence of Serious Adverse Events (SAEs).

  Assessed by the NCI CTCAE version 5.0.

  At the end of each 28 Day cycle for a maximum of 32 cycles

• Determine the recommended Phase 2 Dose (RP2D) of BMF-500.

  Safety, as determined by Dose-Limiting Toxicities (clinically significant Adverse Event) within each dose level assessed NCI CTCAE version 5.0.

  At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period

• Determine the recommended Phase 2 Dose (RP2D) of BMF-500.

  Efficacy within each dose level as determined by composite complete remission (CRc).

  At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period

• Determine the recommended Phase 2 Dose (RP2D) of BMF-500.

  Pharmacovigilance (PK) at each dose level as determined by the maximum plasma concentration (Cmax).

  At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period

• Determine the recommended Phase 2 Dose (RP2D) of BMF-500.

  Pharmacovigilance (PK) at each dose level as determined by area under the curve plasma concentration from time 0 to last quantifiable concentration (AUClast).

  At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period

Secondary Outcomes (7)

• Determine the pharmacokinetics of BMF-500.

  At the end of each cycle (each cycle is 28 days in duration) for 7 cycles

• Determine the pharmacokinetics of BMF-500.

  At the end of Cycle 1 and 2 (each cycle is 28 days in duration)

• 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

• 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

• 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

Study Arms (3)

Arm A: Escalation Phase

EXPERIMENTAL

BMF-500 taken twice daily by participants who are not receiving drugs that inhibit CYP3A4 activity.

Drug: BMF-500

Arm B: Escalation Phase

EXPERIMENTAL

BMF-500 taken twice daily by participants who are receiving necessary azole antifungals that are Strong CYP3A4 inhibitors.

Drug: BMF-500

Arm C: Escalation Phase

EXPERIMENTAL

BMF-500 taken twice daily by participants who are receiving necessary azole antifungals that are moderate CYP3A4 inhibitors.

Drug: BMF-500

Interventions

BMF-500 DRUG

Investigational Product

Arm A: Escalation Phase; Arm B: Escalation Phase; Arm C: Escalation Phase

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.
• Individuals with histologically or pathologically confirmed diagnosis of relapsed or refractory AML 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 strong CYP3A4 inhibitor (excluding other 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.
• Arm C: Participants must have received necessary azole antifungal(s) that are moderate CYP3A4 inhibitors (excluding other moderate CYP3A4 inhibitors) 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 (Cycle 1).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biomea Fusion Inc.: lead

Study Sites (14)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Kentucky - Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

Texas Oncology-PA USOR

Dallas, Texas, 75251, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists

Gainesville, Virginia, 20155, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

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: Accelerated Titration Design, Followed by Modified 3+3

Study Record Dates

• First Submitted: May 18, 2023
• First Posted: June 26, 2023
• Study Start: July 26, 2023
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)