Inotuzumab ozogamicin (InO) is an antibody-drug conjugate composed of a recombinant, humanized immunoglobulin type G, subtype 4 (IgG4) antibody covalently bound to a semisynthetic derivative of calicheamicin via an acid-labile linker. It was developed for the treatment of relapsed or refractory non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). Based on the perceived relatively low immunogenicity risk for this product, a standard approach to immunogenicity testing was utilized during the clinical studies. This manuscript describes the analytical aspects of antibody measurement and highlights the immunogenicity data from clinical studies in patients with hematologic malignancies. Anti-drug antibodies (ADAs) were determined using an enzyme-linked immunosorbent assay for patients with NHL and a bridging electrochemiluminescence assay for patients with ALL. ALL patients who tested positive for ADA were also tested for neutralizing antibodies (pivotal studies only) using a cell-based assay. Immunogenicity assays were validated per current industry practice and regulatory guidelines. Positive ADAs were observed in 7 of 164 (4%) patients with ALL during the pivotal trial. Neutralizing antibodies were not detected in any patients with positive ADAs. No ADAs were detected during the phase I/II ALL study. In NHL studies, antibodies to InO were observed in 27 of 630 (4%) patients. InO clearance was similar between ADA-positive and ADA-negative ALL patients. Standard immunogenicity strategy provided data to evaluate impact on InO efficacy, pharmacokinetics, or other clinical parameters in patients. The incidence of ADA to InO is low and is not clinically meaningful.

中文翻译：

---

非霍奇金淋巴瘤和急性淋巴细胞性白血病患者inotuzumab ozogamicin的临床免疫原性评估

依托珠单抗ozogamicin（InO）是一种抗体-药物偶联物，由重组的人源化G型免疫球蛋白亚型4（IgG4）抗体组成，该抗体通过对酸不稳定的接头与加利车霉素的半合成衍生物共价结合。它被开发用于治疗复发性或难治性非霍奇金淋巴瘤（NHL）和急性淋巴细胞白血病（ALL）。基于该产品相对较低的免疫原性风险，在临床研究期间采用了标准的免疫原性测试方法。该手稿描述了抗体测量的分析方面，并着重介绍了来自血液系统恶性肿瘤患者临床研究的免疫原性数据。对于NHL患者，使用酶联免疫吸附测定法，对于ALL患者，采用桥接电致发光测定法测定抗药物抗体（ADAs）。还使用基于细胞的测定法对所有测试为ADA呈阳性的患者进行了中和抗体测试（仅关键研究）。免疫原性测定已根据当前的行业惯例和法规指南进行了验证。在关键试验期间，在164例ALL患者中有7例（4％）观察到ADA阳性。在任何ADAs阳性的患者中均未检测到中和抗体。在I / II ALL阶段研究中未检测到ADA。在NHL研究中，在630名患者中有27名（4％）观察到了InO抗体。ADA阳性和ADA阴性ALL患者的InO清除率相似。标准的免疫原性策略提供了数据，以评估对患者的InO功效，药代动力学或其他临床参数的影响。ADA对InO的发生率低，在临床上没有意义。