Efficacy, safety, and determination of RP2D of ABBV-383, a BCMA bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM).

作者：Cesar Rodriguez Valdes, Peter M. Voorhees, Anita D’Souza, Alfred Chung, Sascha A. Tuchman, Hana Safah, John T. McKay, Katja Weisel, Raphael Teipel, Neha Korde, Ravi Vij, Orlando Felix Bueno, Tanya Rosenberg, Rajvineeth Kumar Pothacamury, Akshanth Polepally, Aarif Ahsan, Xin Li, Ziyi Jin, Chetasi Talati, Shaji Kumar · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.16_suppl.7531 · 被引用次数：13 · 研究领域：Monoclonal and Polyclonal Antibodies Research、Multiple Myeloma Research and Treatments、Chronic Lymphocytic Leukemia Research

7531 Background: MM eventually becomes refractory to current treatments, and new therapeutic options with convenient dosing and improved safety are needed to enhance patient (pt) adherence, access, and outcomes. ABBV-383 is a distinctive next-generation BCMA x CD3 bispecific antibody composed of 2 high-affinity BCMA-binding domains, a low-affinity CD3-binding domain designed to reduce cytokine release syndrome (CRS) risk, and a silenced Fc tail for an extended half-life allowing convenient dosing. ABBV-383 monotherapy has shown promising activity in the ongoing first-in-human phase 1 trial in RRMM (Vij et al. Blood 2023;142[suppl 1]:3378). Here, safety and efficacy results are reported that support the RP2D of 60mg Q4W as the optimal therapeutic ABBV-383 monotherapy dose. Methods: This phase 1 open-label, dose-escalation/expansion trial (NCT03933735) enrolled pts with RRMM who received ≥3 prior lines of therapy with exposure to PI, IMiD, and anti-CD38 mAb. ABBV-383 regimens explored in the expansion phase included 60mg Q4W and 40 or 60mg Q3W. A modified dexamethasone premedication schedule and shortened CRS monitoring period were implemented in the 60mg Q4W cohort for cycle 1. IV ABBV-383 was administered as a flat dose with no step-up schedule. Treatment was continued until disease progression/unacceptable toxicity. Primary objectives were to assess safety, tolerability, PK, PD, and determine the RP2D. Efficacy evaluation was a secondary objective. TEAEs were assessed per CT...