COVALENT-101: STUDY & BMF-219 BACKGROUND
- Menin, a protein involved in transcriptional regulation, impacting cell cycle control, apoptosis, and DNA damage repair,
plays a direct role in oncogenic signaling in multiple cancers. Inhibition of menin is a novel approach to cancer treatment.
- BMF-219, is an orally bioavailable, potent and selective covalent inhibitor of menin, an important transcriptional
regulator known to play a direct role in oncogenic signaling in multiple cancers.
- Preclinical data of BMF-219 show sustained potent abrogation of menin-dependent oncogenic signaling in vitro and in
- BMF-219 demonstrates strong anti-proliferative effect on various menin-dependent AML cell lines, DLBCL cell lines
representing Double/Triple Hit Lymphoma(DHL/THL), Double Expressor Lymphoma (DEL), and MM cell lines harboring
diverse mutational backgrounds.
- BMF-219 exhibits high potency ex vivo in patient samples from MLL-rearranged and NPM1-mutant AML, THL and MYCamplified DLBCL, and bone marrow mononuclear cells from treatment-naive and R/R MM.
- BMF-219 is supplied as 25 and 100 mg strength capsules for oral administration.
1. Issa, G. C., et al. (2021). Therapeutic implications of menin inhibition in acute leukemias. Leukemia, 35(9), 2482–2495.
2. Anti-tumor activity of irreversible menin inhibitor, BMF-219, in High Grade B-Cell Lymphoma and Multiple Myeloma Preclinical Models. AACR 2022, Abstract 2654
COVALENT-101: STUDY OVERVIEW & DESIGN
- COVALENT-101 is a prospective, open-label, multi-cohort, non-randomized, multicenter, first-in-human, Phase I study evaluating the safety, tolerability, and clinical activity of escalating doses of oral BMF-219 administered once daily in patients with R/R ALL, AML, DLBCL and MM who have received standard therapy.
- Approximately 20 clinical sites in the United States.
COVALENT-101: OBJECTIVES & ENDPOINTS
COVALENT-101: DOSE ESCALATION SCHEME
COVALENT-101: KEY ELIGILIBILITY CRITERIA
Key Inclusion Criteria
- ≥ 18 years with ECOG performance status of 0-2 and an estimated life expectancy of >3 months
- Adequate liver function: Bilirubin ≤ 1.5 ULN; ALT/AST ≤ 2.0 ULN
- Adequate renal function: estimated creatinine clearance (eCrCl) ≥ 60 mL/min (Cohort 1) or eCrCl ≥ 30 mL/min (Cohorts 2 & 3) using the Cockcroft-Gault equation
- Prior treatment-related toxicities resolved to ≤ Grade 2 prior to enrollment
- Adequate washout from prior therapies (e.g., ≥ 60 days from RT; ≥ 60 days from stem cell infusion; ≥ 7 days from biologics or steroids; ≥ 21 days from prior immunotherapy; ≥ 14 days from completion of last chemotherapy
Key Exclusion Criteria
- Known CNS disease involvement
- Prior menin inhibitor therapy
- Clinically significant cardiovascular disease; LVEF <45% Mean QTcF or QTcB of > 470 millisecond (ms)
- Acute or chronic GVHD except disease limited to skin with adequate control using topical steroids
- Concurrent malignancy in the previous 2 years