A Phase 1b Study of Step-up Dosing with ABBV-383, a B-Cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Patients with Relapsed or Refractory Multiple Myeloma

作者：Hira Mian, Muhamed Baljević, Hila Magen, Moshe E. Gatt, Irit Avivi Mazza, Emma Searle, Eben I. Lichtman, John T. McKay, Torben Plesner, César A. Rodríguez, Neha Korde, Hana Safah, Iuliana Vaxman, Chetasi Talati, Anders Svensson, Ziyi Jin, Shane Lee, Thomas Doerr, Rajvineeth Kumar Pothacamury, Tanya S Rosenberg, Akshanth R. Polepally, Jeremy A. Ross, Shaji Kumar · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-206912 · 被引用次数：5 · 研究领域：Multiple Myeloma Research and Treatments、Monoclonal and Polyclonal Antibodies Research、Lymphoma Diagnosis and Treatment

Introduction Patients (pts) with multiple myeloma (MM) eventually become refractory to current treatments. There is an unmet need for new therapies with durable efficacy, favorable safety, and simplified dosing schedules. ABBV-383 is a unique BCMA x CD3 bispecific antibody T-cell engager comprising bivalent high-avidity BCMA binding domains, a low-affinity CD3-binding domain designed to minimize cytokine release and the risk for cytokine release syndrome (CRS), and a silenced Fc tail for extended half-life enabling dosing convenience. In an ongoing first-in-human (FIH) study (NCT03933735) in heavily pretreated pts with relapsed or refractory (RR) MM, ABBV-383 monotherapy (60 mg Q4W) resulted in deep and durable responses. Introduction of a modified dexamethasone (Dex) premedication (premed) schedule in cycle (C) 1 lowered incidence and severity of CRS (43% overall; 5% grade ≥2) vs pts treated with low Dex (71% overall; 20% grade ≥2) (JCO 2024;42[suppl 16]:7531). We now report results of Arm A of the open-label, phase 1b study (NCT05650632) evaluating 1 step-up dose (SUD) of ABBV-383 as a strategy to mitigate the risk of severe CRS and further assess ABBV-383 activity in pts with RRMM. Methods This study is enrolling pts with RRMM, ECOG performance status ≤2, and documented evidence of progression during or after the last treatment. Pts must have received ≥3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody...