BMF-219 Yields Responses in Relapsed/Refractory AML With Menin-Dependent Mut

Treatment with the Menin inhibitor BMF-219 at 500 mg once daily (dose level [DL] 4) achieved responses in patients with relapsed or refractory acute myeloid leukemia (AML) and known Menin-dependent mutations, according to topline analysis data from the phase 1 COVALENT 101 trial (NCT05153330).¹

The preliminary activity shown with BMF-219 corresponds with preclinical data. Further, the agent was well-tolerated in patients.

Out of 5 patients with AML who had either a KMT2Ar/MLL1r mutation, NPM1 mutation, MLL-PTD, or NUP98 fusion and who were treated with BMF-219 at 500 mg or 125 mg, 2 complete responses were observed. Responses occurred within observed within the first two 28-day treatment cycles.

Overall, 20 patients with AML received BMF-219 during the dose-escalation phase of the study. No QTc prolongation was observed, and no dose-limiting toxicities were observed at DL4. Based on these findings, BMF-219 is now being administered at DL5.

COVALENT-101 is a first-in-human, dose-escalation, and dose-expansion study evaluating the use of BMF-219 in adult patients with AML, acute lymphocytic leukemia with KMT2A/ MLL1r mutations, diffuse large B-cell lymphoma, multiple myeloma, chronic lymphocytic leukemia, and small lymphocytic lymphoma. The primary end point of the study is optimal biologic dose and recommended phase 2 dose of BMF-219. The secondary end point of the study is safety determined by treatment-emergent adverse events.²

Patients aged 18 years or older are eligible to enroll in COVALENT-101 given their disease is histologically or cytologically confirmed, they are refractory to or progressed on an anti-cancer therapy, have an ECOG performance score of 0-2, and adequate organ function.

Individuals excluded from the study are those with certain disease subtypes of disease, white blood cell count > 50,000/μL, known central nervous system involvement, prior treatment with a Menin inhibitor, HIV, hepatitis B, or hepatitis C, serious infection, or active uncontrolled acute or chronic systemic fungal, bacterial, or viral infection.

“We are very excited to share these early findings confirming that our targeted, covalently binding Menin inhibitor, BMF-219, can elicit profound and rapid responses in patients with Menin inhibitor-sensitive acute leukemia even at this dose level, which we believe we can further build on,” said Steve Morris, MD, chief medical officer of Biomea, in a press release. “Notably these complete remissions were achieved within the first two cycles of BMF-219 therapy in relapsed/refractory [patients with] AML who had limited therapeutic options and an overall poor prognosis. We are continuing to dose escalate and are looking forward to identifying the recommended phase 2 dose within the next several months.”

_REFERENCES:

_{1. BMF-219 induces complete responses in target acute myeloid leukemia (AML) patient population. News release. Biomea Fusion, Inc. July 24, 2023. Accessed July 25, 2023. https://tinyurl.com/yr56yuma}

_{2. Study of BMF-219, a covalent menin inhibitor, in adult patients with AML, ALL (With KMT2A/ MLL1r, NPM1 Mutations), DLBCL, MM, and CLL/SLL. ClincialTrials.gov. Updated May 3, 2023. Accessed July 25, 2023. https://tinyurl.com/4cuecp7c}