First Patient Dosed With Menin Inhibitor BMF-219 in COVALENT-101 Trial in CLL

Thomas Butler

The first patient in the chronic lymphocytic leukemia (CLL) cohort has been dosed in the phase 1 COVALENT-101 trial (NCT05153330), which is evaluating the first-in-class covalent menin inhibitor BMF-219, in patients with relapsed/refractory acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), multiple myeloma, and CLL.^1,2

“Despite the advances in the treatment of CLL, we know that the majority of patients relapse and are in need of a new, novel therapy,” Thomas Butler, chief executive officer and chairman of the board of Biomea, said in a press release. “Based on the remarkable preclinical data we presented at [the 2022 ASCO Annual Meeting] of BMF-219’s effect in CLL models, including comparisons to currently available treatments, we believe BMF-219 could represent a transformative treatment option for [patients with] CLL.”

COVALENT-101 is a phase 1, open-label, multi-center, dose-escalation and dose-expansion study that was designed to assess the safety, tolerability, and pharmacokinetic and pharmacodynamic activity of BMF-219, administered orally in patients with relapsed/refractory acute leukemias, including subpopulations where menin inhibitors are expected to provide benefit. Subpopulations included patients with MLL1/KMT2A gene rearrangements or NPM1 mutations, multiple myeloma, and DLBCL. The study design has since been updated to include a cohort for patients with relapsed/refractory CLL.

To be eligible for enrollment, in addition to receiving a refractory diagnosis of one of the malignancies, patients had to be at least 18 years of age and have an ECOG performance status between 0 and 2 with a life expectancy of more than 3 months, adequate organ function, and be willing to use adequate birth control measures during the trial and for at least 90 days thereafter.

Patients were excluded if they had acute promyelocytic leukemia, chronic myeloid leukemia in blast crisis, primary mediastinal B-cell lymphoma, DLBCL transformed from diseases other than indolent non-Hodgkin lymphoma, active plasma cell leukemia, myeloma with amyloidosis, systemic light chain amyloidosis, or a known or suspected history of Richter’s transformation.

Additionally, patients were ineligible for enrollment if had a white blood count that exceeded 50,000/μL, known central nervous involvement, prior menin inhibitor therapy, a known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen, a pre-existing disorder predisposing them to a serious or life-threatening infection, or an active uncontrolled acute or chronic systemic fungal, bacterial, or viral infection.

Research presented at the 2022 ASCO Annual Meeting demonstrated potent single-agent antitumor activity with BMF-219 against CLL patient samples, representing a broad spectrum of mutational profiles, including those with poor prognostic mutations, such as TP53 and NOTCH1, or chromosomal aberrations such as deletion(13q), trisomy 12, and complex karyotype.³ Additionally, BMF-219 elicited near complete response even in patient samples resistant to several standard-of-care agents.

“I am very proud of our research and translational team’s ability to further elucidate the central role of the scaffold protein menin and identify a host of specific subsets across various cancers where BMF-219 is achieving robust preclinical results. We are very excited to continue to advance this new therapeutic approach for patients with multiple liquid and solid tumors, many of whom have very little remaining alternatives,” Butler concluded.

References

1. Biomea Fusion Announces First Patient Dosed with Chronic Lymphocytic Leukemia (CLL) in COVALENT-101 Trial. News release. Biomea Fusion Inc. October 27, 2022. Accessed November 1, 2022. https://yhoo.it/3WeNdv3
2. Study of BMF-219, a covalent menin inhibitor, in adult patients with AML, ALL with KMT2A/ MLL1r, NPM1 and other mutations. ClinicalTrials.gov. Updated October 26, 2022. Accessed November 1, 2022. https://clinicaltrials.gov/ct2/show/NCT05153330
3. Somanath P, Lu D, Law B, et al. Preclinical activity of irreversible menin inhibitor, BMF-219, in chronic lymphocytic leukemia. J Clin Oncol. 2022;40(suppl 16):7541. doi:10.1200/JCO.2022.40.16_suppl.7541