Phase 1b study of the anti-CD38 antibody mezagitamab in patients with relapsed/refractory multiple myeloma

Blood Neoplasia Pub Date : 2024-09-18 DOI:10.1016/j.bneo.2024.100043

Amrita Y. Krishnan , Krina K. Patel , Meera Mohan , Sundar Jagannath , Ruben Niesvizky , Rebecca W. Silbermann , Ziji Yu , Tao Long , Scott R. P. McDonnell , Deborah Berg , Keith E. Stockerl-Goldstein

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Abstract

This phase 1b trial aimed to determine the safety, tolerability, and preliminary efficacy of mezagitamab, a subcutaneously administered anti-CD38 monoclonal antibody, in patients with relapsed/refractory multiple myeloma (RRMM). Eligible patients had received ≥3 prior lines of treatment, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and a steroid, or ≥2 prior lines in which 1 included a PI + IMiD, and were refractory or intolerant to ≥1 IMiD and ≥1 PI. Fifty patients were enrolled: 44 received mezagitamab monotherapy (dose-escalating cohorts at 45-1200 mg) and 6 received mezagitamab 300 mg in combination with pomalidomide plus dexamethasone. Patients received mezagitamab weekly for 8 doses, every other week for 8 doses, and monthly thereafter. No dose-limiting toxicities were reported with single-agent mezagitamab, and the recommended phase 2 dose was determined as 600 mg. The most common drug-related treatment-emergent adverse events (TEAEs) were fatigue in the monotherapy cohort (9/44 patients) and neutropenia in the combination cohort (4/6 patients); neutropenia was the only drug-related grade ≥3 TEAE to occur in >1 patient. No infusion reactions occurred, and 4 injection-site reactions were reported. Three patients discontinued treatment due to TEAEs. Among the 22 patients receiving 600 mg mezagitamab, the overall response rate was 47%, and the median duration of response was 22.1 months. Mezagitamab outcomes were comparable to those reported with other anti-CD38 therapies in patients with advanced RRMM. Further development of mezagitamab in myeloma is not planned, but studies are underway in autoimmune conditions. This trial was registered at www.ClinicalTrials.gov as #NCT03439280.

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针对复发性/难治性多发性骨髓瘤患者的抗CD38抗体美扎吉他单抗1b期研究

摘要这项1b期试验旨在确定复发性/难治性多发性骨髓瘤（RRMM）患者皮下注射抗CD38单克隆抗体mezagitamab的安全性、耐受性和初步疗效。符合条件的患者既往接受过≥3种治疗，包括一种免疫调节药物（IMiD）、一种蛋白酶体抑制剂（PI）和一种类固醇，或既往接受过≥2种治疗，其中1种包括PI+IMiD，并且对≥1种IMiD和≥1种PI难治或不耐受。50名患者入选：44名患者接受了麦扎吉单抗单药治疗（剂量递增组为45-1200毫克），6名患者接受了300毫克麦扎吉单抗联合泊马度胺加地塞米松治疗。患者每周接受一次麦扎吉单抗治疗，共8次，隔周一次，共8次，之后每月一次。单药麦扎吉单抗未出现剂量限制性毒性反应，第二阶段的推荐剂量被确定为600毫克。最常见的药物相关治疗突发不良事件（TEAEs）是单药治疗队列中的疲劳（9/44例患者）和联合治疗队列中的中性粒细胞减少症（4/6例患者）；中性粒细胞减少症是唯一发生在>1例患者身上的药物相关≥3级TEAE。未发生输液反应，报告了4例注射部位反应。3名患者因出现TEAE而中断治疗。在接受600毫克美扎吉单抗治疗的22名患者中，总反应率为47%，中位反应持续时间为22.1个月。在晚期RRMM患者中，美扎吉单抗的疗效与其他抗CD38疗法的疗效相当。目前尚未计划在骨髓瘤领域进一步开发麦扎吉单抗，但正在进行自身免疫疾病的研究。该试验已在 www.ClinicalTrials.gov 注册，注册号为 #NCT03439280。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Blood Neoplasia

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