PURPOSE ABBV-838 is an antibody-drug conjugate targeting a unique epitope of CD2 subset 1, a cell-surface glycoprotein expressed on multiple myeloma cells. This phase I/Ib first-in-human, dose-escalation study (trial registration ID: NCT02462525) evaluated the safety, pharmacokinetics, and preliminary activity of ABBV-838 in patients with relapsed and refractory multiple myeloma (RRMM). PATIENTS AND METHODS Eligible patients (≥18 years) received ABBV-838 (3+3 design) intravenously starting from 0.6 mg/kg up to 6.0 mg/kg for 3-week dosing intervals (Q3W). Patients could continue ABBV-838 for up to 24 months. Assessment of alternate dosing intervals (Q1W and Q2W) was conducted in parallel. RESULTS As of March 2017, 75 patients received at least one dose of ABBV-838. The most common any-grade treatment-emergent adverse events (TEAE) were neutropenia and anemia (28.0% each), fatigue (26.7%), and nausea (25.3%). Grade 3/4/5 TEAEs were reported in 73.3% of patients across all treatment groups; most common were neutropenia (20.0%), anemia (18.7%), and leukopenia (13.3%). Grade 3/4/5 ABBV-838-related TEAEs were reported by 40.0% of patients across all treatment groups. Overall, 4.0% of patients experienced TEAEs leading to death, none ABBV-838 related. The MTD was not reached; the selected recommended dose for the expansion cohort was 5.0 mg/kg Q3W. Pharmacokinetic analysis showed that exposure was approximately dose proportional. The overall response rate was 10.7%; very good partial responses and partial responses were achieved by 2 (2.7%) and 6 (8.0%) patients, respectively. CONCLUSIONS These results demonstrate that ABBV-838 is safe and well-tolerated in patients with RRMM with a very limited efficacy.

中文翻译：

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针对复发性和难治性多发性骨髓瘤患者的靶向SLAMF7 / CS1的抗体-药物偶联物ABBV-838的人类首次I期研究。

目的ABBV-838是一种抗体-药物偶联物，靶向CD2亚群1的独特表位，CD2亚群1是在多发性骨髓瘤细胞上表达的细胞表面糖蛋白。这项I / Ib人体首次剂量递增研究（试验注册号：NCT02462525）评估了ABBV-838在复发和难治性多发性骨髓瘤（RRMM）患者中的安全性，药代动力学和初步活性。患者和方法符合条件的患者（≥18岁）接受静脉注射ABBV-838（3 + 3设计），剂量从0.6 mg / kg到6.0 mg / kg，为期3周（Q3W）。患者可以继续使用ABBV-838长达24个月。并行评估备用加药间隔（Q1W和Q2W）。结果截至2017年3月，有75名患者接受了至少一剂ABBV-838。最常见的任何等级的治疗紧急不良事件（TEAE）是中性粒细胞减少和贫血（各28.0％），疲劳（26.7％）和恶心（25.3％）。在所有治疗组中，有73.3％的患者报告了3/4/5级TEAE；最常见的是中性粒细胞减少症（20.0％），贫血（18.7％）和白细胞减少症（13.3％）。在所有治疗组中，有40.0％的患者报告了3/4/5级与ABBV-838相关的TEAE。总体而言，有4.0％的患者经历了TEAE导致死亡，与ABBV-838没有关系。未达到MTD；扩展队列的推荐推荐剂量为5.0 mg / kg Q3W。药代动力学分析表明，暴露与剂量成正比。总体回应率为10.7％；2（2.7％）和6（8.0％）的患者分别获得了非常好的部分缓解和部分缓解。