BMF-219 for Blood Cancers

No longer recruiting at 43 trial locations

Overseen By Mona Vimal

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Biomea Fusion

Disqualifiers: APL, CML, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called BMF-219 (also known as Icovamenib, a covalent menin inhibitor) for individuals with certain blood cancers. The goal is to determine the optimal dose and assess its safety and effectiveness for conditions like acute leukemia, lymphoma, multiple myeloma, and chronic lymphocytic leukemia. Participants will take BMF-219 orally, and the trial includes different groups based on cancer type and previous treatments. It suits adults whose cancer has returned or did not respond to prior treatments, impacting their daily life. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have progressed on or after your most recent anti-cancer therapy to be eligible.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that BMF-219 is likely to be safe for humans?

Research has shown that BMF-219, a new pill under testing, might help treat certain blood cancers like acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). In some studies, BMF-219 has shown promise. For instance, in one study, two out of five patients with a specific type of AML saw their cancer completely disappear.

These studies are in the early stages regarding safety. The main goal is to assess the drug's safety and determine the right dose. Few reports about side effects have emerged, but as this is a Phase 1 study, doctors closely monitor patients to ensure the treatment is safe. This phase focuses on ensuring the drug isn't harmful, so participants undergo regular checks for any negative effects.

So far, BMF-219 has shown enough potential to continue testing. However, anyone considering joining a trial should discuss possible risks and benefits with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

BMF-219 is unique because it targets blood cancers with a novel mechanism of action. Unlike standard treatments like chemotherapy and immunotherapy, which often have broad effects on both healthy and cancerous cells, BMF-219 is designed to specifically inhibit menin, a protein that plays a key role in the survival of cancer cells in blood cancers. This targeted approach not only aims to be more effective but also potentially reduces side effects compared to traditional treatments. Researchers are excited as this could lead to a breakthrough in treating difficult-to-manage blood cancers such as acute leukemia, diffuse large B-cell lymphoma, multiple myeloma, and chronic lymphocytic leukemia/small lymphocytic lymphoma.

What evidence suggests that BMF-219 could be an effective treatment for blood cancers?

Research has shown that BMF-219, a covalent menin inhibitor, may help treat various blood cancers. In this trial, participants will receive BMF-219 in different phases to assess its safety and efficacy. Studies have found that it can combat cancer in conditions like acute leukemia and multiple myeloma by interfering with proteins that promote cancer cell growth. Early tests demonstrated that BMF-219 significantly reduced or even eliminated cancer cells. It also lowers levels of BCL2, a protein that often aids cancer cell survival. These findings suggest that BMF-219 could be a strong treatment option for patients with these challenging conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Steve Morris, MD

Principal Investigator

Biomea Fusion Inc.

Are You a Good Fit for This Trial?

Adults with certain blood cancers like AML, ALL with specific mutations, DLBCL, MM, and CLL/SLL can join this trial. They must have relapsed or refractory cancer despite previous treatments, be over 18 years old with good organ function and willing to use birth control. People are excluded if they have active CNS involvement by their cancer or a history of certain other conditions.

Inclusion Criteria

My lymphoma has worsened or remained despite treatment.

I can care for myself and doctors expect me to live more than 3 months.

My organs are working well.

Exclusion Criteria

I have plasma cell leukemia, myeloma with amyloidosis, or systemic light chain amyloidosis.

I have APL or CML in blast crisis.

My condition is primary mediastinal B-cell lymphoma or DLBCL not from indolent NHL.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of BMF-219 to identify the Optimal Biologic Dose (OBD) and Recommended Phase 2 Dose (RP2D)

4 weeks

Daily oral administration

Dose Expansion

Participants receive BMF-219 at the OBD/RP2D to further assess safety and efficacy

4 weeks

Daily oral administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BMF-219

Trial Overview The study is testing BMF-219, an oral drug designed to block menin's action in the body. It's for adults who've seen their blood cancer return or not respond to treatment. The trial will gradually increase doses to find the safest and most effective level.

How Is the Trial Designed?

Group I: Dose Expansion Experimental Treatment 1 Intervention

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.

Group II: Dose Escalation Phase Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Biomea Fusion

Lead Sponsor

Trials

1

Recruited

60+

Biomea Fusion Inc.

Lead Sponsor

Trials

5

Recruited

780+

Published Research Related to This Trial

In a phase Ib study involving 89 patients with advanced solid tumors, the combination of binimetinib (a MEK inhibitor) and buparlisib (a PI3K inhibitor) showed some efficacy, particularly in RAS/BRAF-mutant ovarian cancer, where 12% of patients achieved a partial response.

However, the treatment was associated with significant toxicities, leading to a lower than expected dose intensity, suggesting that alternative dosing strategies, like pulsatile dosing, may be necessary to improve safety and tolerability in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations. Bardia, A., Gounder, M., Rodon, J., et al.[2023]

Revumenib, a menin inhibitor, showed a 63% response rate in a phase II study for patients with relapsed or refractory acute leukemias with KMT2A rearrangements.

In a phase I trial, combining revumenib with three chemotherapies resulted in complete remissions in patients with acute myeloid leukemia, highlighting its potential effectiveness in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Menin Inhibitors Trigger Leukemia Remissions. [2023]

The combination of the allosteric MEK inhibitor refametinib and sorafenib was found to be well tolerated in a phase I study involving 32 patients, with the maximum tolerated dose established at refametinib 50 mg and sorafenib 400 mg, showing common side effects like diarrhea and fatigue.

This treatment effectively reduced ERK phosphorylation in tumors, particularly in patients with KRAS or BRAF mutations, and stabilized disease in about half of the participants, with one patient experiencing a partial response lasting around one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Combination Therapy with Refametinib plus Sorafenib in Patients with Advanced Cancer. Adjei, AA., Richards, DA., El-Khoueiry, A., et al.[2022]

A new class of small-molecule inhibitors targeting the menin-MLL protein interaction has been developed, with the compound M-89 showing a very strong binding affinity (Kd value of 1.4 nM) and effective engagement of menin at low concentrations.

M-89 demonstrated significant anti-leukemic activity, inhibiting cell growth in MLL fusion leukemia cell lines with IC50 values of 25 nM and 55 nM, while being over 100 times more selective for these cells compared to a leukemia cell line without MLL fusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structure-Based Discovery of M-89 as a Highly Potent Inhibitor of the Menin-Mixed Lineage Leukemia (Menin-MLL) Protein-Protein Interaction. Aguilar, A., Zheng, K., Xu, T., et al.[2020]

In a phase II study involving 98 patients with BRAFV600E-mutant metastatic non-small-cell lung cancer (NSCLC), the combination of encorafenib and binimetinib achieved a confirmed objective response rate of 75% in treatment-naïve patients and 46% in previously treated patients, indicating significant efficacy.

The treatment was generally well-tolerated, with common side effects including nausea (50%) and diarrhea (43%), but it also led to dose reductions in 24% of patients and one serious adverse event of intracranial hemorrhage, highlighting the importance of monitoring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. Riely, GJ., Smit, EF., Ahn, MJ., et al.[2023]

M-1121 is a new oral inhibitor that targets the menin-MLL protein interaction, showing complete and lasting tumor regression in acute leukemia with MLL rearrangements, while having no effect on leukemia with wild-type MLL.

The drug works by covalently binding to a specific site on the menin protein, leading to reduced expression of key genes associated with leukemia, and demonstrates strong antitumor activity in animal models at safe doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of M-1121 as an Orally Active Covalent Inhibitor of Menin-MLL Interaction Capable of Achieving Complete and Long-Lasting Tumor Regression. Zhang, M., Aguilar, A., Xu, S., et al.[2022]

M-525 is a first-in-class small-molecule inhibitor that irreversibly targets the menin-MLL interaction, showing high potency at sub-nanomolar concentrations and effectively inhibiting cell growth in MLL leukemia cells.

This compound demonstrates over 30 times greater potency compared to reversible inhibitors and selectively suppresses MLL-regulated gene expression, indicating its potential as a promising therapeutic strategy for treating MLL leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of the First-in-Class, Highly Potent Irreversible Inhibitor Targeting the Menin-MLL Protein-Protein Interaction. Xu, S., Aguilar, A., Xu, T., et al.[2022]

The combination of encorafenib and binimetinib was found to be safe and showed promising activity in patients with BRAF V600E-mutant solid tumors, with a recommended phase 2 dose established for further studies.

In phase II, the treatment resulted in confirmed responses in 67% of BRAFi-naïve melanoma patients, indicating significant efficacy, while the most common serious side effect was increased alanine aminotransferase levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAFV600E/K -mutant Solid Tumors. Sullivan, RJ., Weber, J., Patel, S., et al.[2021]

The study identifies menin as a crucial factor in MLL1-mediated leukemia, suggesting that inhibiting the menin-MLL1 interaction could be an effective strategy to combat this type of cancer.

A newly designed macrocyclic peptidomimetic inhibitor, MCP-1, shows exceptional potency with a binding affinity of 4.7 nM, making it over 600 times more effective than the original peptide, indicating its potential as a lead compound for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structure-based design of high-affinity macrocyclic peptidomimetics to block the menin-mixed lineage leukemia 1 (MLL1) protein-protein interaction. Zhou, H., Liu, L., Huang, J., et al.[2019]

M-808 is a newly developed covalent menin inhibitor that shows strong effectiveness in inhibiting leukemia cell growth at low nanomolar concentrations, indicating its potential as a powerful treatment for MLL leukemia.

In mouse models, M-808 not only inhibited tumor growth but also achieved partial tumor regression, demonstrating its efficacy and safety at a well-tolerated dosing schedule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of M-808 as a Highly Potent, Covalent, Small-Molecule Inhibitor of the Menin-MLL Interaction with Strong In Vivo Antitumor Activity. Xu, S., Aguilar, A., Huang, L., et al.[2023]

The combination of encorafenib and binimetinib is now the standard treatment for patients with advanced melanoma harboring BRAF V600 mutations, based on the phase III COLUMBUS study.

While this combination therapy is effective, it is associated with specific adverse events such as serious retinopathy and cardiovascular toxicities, highlighting the importance of proactive management to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment experience with encorafenib plus binimetinib for BRAF V600-mutant metastatic melanoma: management insights for clinical practice. Augustyn, K., Joseph, J., Patel, AB., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05153330

NCT05153330 | Study of BMF-219, a Covalent Menin ... 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 ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265023010777

AML-522 COVALENT-101: Phase I Study of BMF-219, a ... BMF-219 is the first investigational menin inhibitor in clinical development to show potential as a therapeutic agent in hematologic malignancies outside of ...

3. investors.biomeafusion.com investors.biomeafusion.com/news-releases/news-release-details/bmf-219-induces-complete-responses-target-acute-myeloid-leukemia

BMF-219 Induces Complete Responses in Target Acute ... Additionally, BMF-219 has shown anticancer efficacy in multiple in vitro, in vivo, and ex vivo models of acute leukemia, multiple myeloma, ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT367478

Preclinical activity of irreversible Menin inhibitor, BMF-219, ... We previously reported the ability of BMF-219, a selective, irreversible menin inhibitor, to downregulate the expression of BCL2 in acute leukemia cells.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11959225/

Complete remission of NUP98 fusion-positive acute ... BMF-219 (icovamenib) is a small molecule designed to disrupt interactions of menin with various proteins, such as KMT2A and JunD, which regulate multiple ...

6. onclive.com onclive.com/view/first-patient-dosed-with-menin-inhibitor-bmf-219-in-covalent-101-trial-in-cll

First Patient Dosed With Menin Inhibitor BMF-219 in ... The first patient in the chronic lymphocytic leukemia cohort has been dosed in the phase 1 COVALENT-101 trial, which is evaluating the ...

7. investors.biomeafusion.com investors.biomeafusion.com/news-releases/news-release-details/biomea-fusion-present-new-preclinical-data-showing-bmf-219s

Biomea Fusion to Present New Preclinical Data Showing BMF ... BMF-219 is the first investigational menin inhibitor in clinical development to show potential as a therapeutic agent for CLL BMF-219, ...