Phase 1b study of bleximenib in combination with venetoclax in Acute Myeloid Leukemia with KMT2A or NPM1 alterations

作者：J. O'Nions, Andrew Wei, Jordi Esteve, Ibrahim Aldoss, A. Alfonso-Piérola, Alicia Allred, J. Alonso‐Dominguez, Laura Barreyro, P. Bories, Nikki Daskalakis, M. D. Della Porta, H. Döhner, Amber D’Souza, James Dugan, Amir T Fathi, Pasquale L Fedele, Lucille Ferrante, Rachel Kobos, A. Garrido, Sara Garrido Paniagua, Christina Drenberg Guttke, E. Gyan, Brett Hiebert, E. Jabbour, D. Trancucci, Naa Sackey, M. Jentzsch, H. Kantarjian, Marina Konopleva, J. Krönke, M. Hütter-Krönke, C. Loefgren, Oliver Lomas, Valentina Mancini, Daniel Morillo, Kathryn Packman, C. Papayannidis, Christian Récher, C. Röllig, O. Salamero, Prathap Nagaraja Shastri, T. Sauer, Dr. Emma Searle, N. Tovar, Nicolas Vallet, Lachlin Vaughan, Paresh Vyas, U. Platzbecker, S. Garciaz · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-5200 · 被引用次数：6

Objective Bleximenib is a potent, selective menin inhibitor with activity in NPM1-mutated (NPM1m)or KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML), now in Phase 3 development in combination with AML-directed therapies. Phase 1 data with bleximenib 100 mg twice daily (BID) dose in combination AML-directed therapies in participants (pts) with relapsed/refractory (R/R) or newly diagnosed (ND) AML were previously reported (Wei, EHA 2025). We now report the evaluation of safety and efficacy data for the all-oral combination of the bleximenib + venetoclax (VEN) doublet in pts with R/R AML harboring KMT2A or NPM1 alterations (Cohort A1). Methods ALE1002 (NCT05453903) is an ongoing Phase 1b, multicenter, dose-finding study exploring bleximenib in combination with AML-directed therapies. In Cohort A1, pts with R/R AML received VEN in combination with oral bleximenib at 15–100 mg twice daily (BID) continuously. VEN dosing was guided by the label, with ramp-up followed by a plateau dose of 400 mg daily in 28-day cycles. Bleximenib started on Day 4, after VEN ramp-up. Safety analysis includes all dosed pts. Relative dose intensity (RDI) is the total bleximenib dose received divided by total planned doses of bleximenib for a 28-day cycle. Intention-to-treat efficacy analysis includes NPM1m or KMT2Ar AML pts receiving bleximenib 50 mg or 100 mg BID in combination with VEN, including pts who discontinued prior to first disease evaluation. Results As of July 2025, 15 pts received b...