A First in Human Study of VOB560 in Combination with MIK665 in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma, Acute Myeloid Leukemia, or Multiple Myeloma

作者：Harinder Gill, Ine Moors, Kimmo Porkka, Yakir Moshe, Sung Soo Yoon, Naval Daver, Enrique M. Ocio, Masafumi Fukaya, Tim Sauer, Maria-Victoria Mateos, Frank Stegelmann, Marta Ubezio, Alessia Campagna, Massimo Magagnoli, Heiko Maacke, Laurent Susini, Kae Ishihara, I Filipe, Xiaozhou Zhang, Richard Ducray, Lidiya Bebrevska, Ensar Halilovic, Amy Luyt, Armando Santoro · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-199074 · 被引用次数：3 · 研究领域：Acute Myeloid Leukemia Research

Background: Patients with relapsed and refractory (R/R) acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM) require effective treatment options due to their high mortality rates. The inhibition of 2 anti-apoptotic proteins, B-cell lymphoma 2 (BCL2) and myeloid cell leukemia 1 (MCL1), has shown promise as a therapeutic approach for these cancers. Two novel BH3 mimetics, VOB560 and MIK665, selectively inhibit BCL2 and MCL1, respectively, induce apoptosis in hematological cancer cells and showed efficacy in preclinical models. In combination, VOB560 and MIK665 demonstrated strong synergy and promoted cell death in various hematological cancer models. VOB560 binds to BCL2, disrupting its interaction with pro-apoptotic proteins, causing cell death. MIK665 selectively inhibits MCL1, activating caspases and promoting cell death. Here we report the early clinical findings of the combination of VOB560 and MIK665 from the dose escalation phase in the treatment of hematological malignancies. Methods: This was a phase 1b, open-label, multi-center, dose-escalation/-expansion study (NCT04702425) in patients with R/R NHL, AML or MM. In the escalation phase, VOB560 was administered weekly (QW) intravenously (IV) at 25 and 50 mg in combination with MIK665 administered IV at 25 and 50 mg QW. Primary objectives of the dose-escalation phase were to characterize the safety and tolerability of VOB560 in combination with MIK665, and to identify the maximum tolerated ...