This multicenter, phase I, open-label dose escalation study evaluated safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of inebilizumab in Japanese patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), or multiple myeloma (MM) who were ineligible for hematopoietic stem cell transplantation. Patients received inebilizumab 2, 4, or 8 mg/kg intravenously on days 1 and 8 of the first 28-day cycle, and once every 28 days thereafter, with a 12 mg/kg cohort added. Twenty patients (11 FL, six DLBCL, two CLL, and one MM) received inebilizumab at four dose levels (2 mg/kg cohort, n = 3; 4 mg/kg cohort, n = 7; 8 mg/kg cohort, n = 4; 12 mg/kg cohort, n = 6). Three patients experienced dose-limiting toxicities: grade 4 neutropenia/grade 3 leukopenia (n = 1, 12 mg/kg) and grade 3 infusion reaction (n = 1 each, 4 mg/kg and 12 mg/kg); the maximum tolerated dose was 8 mg/kg. Four (three FL and one DLBCL) patients achieved complete response; eight (six FL and two DLBCL) achieved partial response. Overall response rate was 60%. Over the dose ranges evaluated, the pharmacokinetic profile of inebilizumab in Japanese patients was generally dose proportional. This phase I study showed acceptable toxicity and preliminary and promising efficacy of inebilizumab in patients with relapsed/refractory FL and DLBCL.

中文翻译：

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在日本患有复发性或难治性B细胞淋巴瘤和多发性骨髓瘤的日本患者中，一项抗人胆管炎的人源性抗CD19单克隆抗体inebilizumab的多中心I期研究。

这项多中心，I期开放标签剂量递增研究评估了inebilizumab在日本复发/难治性弥漫性大B细胞淋巴瘤（DLBCL），慢性淋巴细胞性白血病（CLL）患者中的安全性，耐受性，药代动力学和初步抗肿瘤活性，不适合进行造血干细胞移植的滤泡性淋巴瘤（FL）或多发性骨髓瘤（MM）。患者在第一个28天周期的第1天和第8天静脉注射inebilizumab 2、4或8 mg / kg，此后每28天接受一次，并添加了12 mg / kg队列。20名患者（11例FL，6例DLBCL，2例CLL和1例MM）以四种剂量水平（2 mg / kg队列，n = 3； 4 mg / kg队列，n = 7； 8 mg / kg队列，n）接受了inebilizumab = 4； 12 mg / kg队列，n = 6）。三名患者出现了剂量限制性毒性：4级中性粒细胞减少症/ 3级白细胞减少症（n = 1，12 mg / kg）和3级输液反应（n = 1，分别为4 mg / kg和12 mg / kg）；最大耐受剂量为8 mg / kg。4名（3名FL和1名DLBCL）患者完全缓解；八个（六个FL和两个DLBCL）实现了部分响应。总体回应率为60％。在评估的剂量范围内，伊尼单抗在日本患者中的药代动力学特征通常与剂量成正比。这项第一阶段研究显示，非尼珠单抗在复发性/难治性FL和DLBCL患者中具有可接受的毒性以及初步和有希望的疗效。总体回应率为60％。在评估的剂量范围内，伊尼单抗在日本患者中的药代动力学概况通常与剂量成比例。这项第一阶段研究显示，非尼珠单抗在复发性/难治性FL和DLBCL患者中具有可接受的毒性以及初步和有希望的疗效。总体回应率为60％。在评估的剂量范围内，伊尼单抗在日本患者中的药代动力学特征通常与剂量成正比。这项第一阶段研究显示，非尼珠单抗在复发性/难治性FL和DLBCL患者中具有可接受的毒性以及初步和有希望的疗效。