评估了针对程序化细胞死亡-1的全人源免疫球蛋白G4单克隆抗体cemiplimab在多种肿瘤类型患者中的免疫原性。利用经过验证的桥联免疫测定监测针对cemiplimab的抗药物抗体（ADAs）。为了在测定中识别ADA阳性样本，通过分析来自不同肿瘤类型的混合人群的基线临床研究样本，建立了由统计确定的切割点，并使用该验证切割点评估所有后续研究的免疫原性。监管指南要求验证ADA测定切割点在不同患者群体中适用。因此，对于cemiplimab ADA测定，我们评估了每个新的肿瘤学人群是否与用于确定切割点的验证人群相当。通过使用已建立的统计方法对来自8种不同肿瘤类型的2393个个体血清样本与验证人群的测定进行比较，未观察到显著差异。在各种肿瘤类型中，cemiplimab的免疫原性较低，在每两周静脉注射剂量为3毫克/千克和每3周静脉注射剂量为350毫克的条件下，总体治疗相关ADA年发生率分别为1.9％和2.5％。此外，在ADA阳性样本中未检测到对cemiplimab的中和抗体，并且cemiplimab ADAs对药代动力学没有观察到的影响。某些疾病（如免疫和炎症性疾病）可能需要研究特异切削点，然而，根据这个分析，对于cemiplimab的每个新的肿瘤学疾病适应证，不需要研究内切削点。本文章受版权保护。版权所有。

The immunogenicity of cemiplimab, a fully human immunoglobulin G4 monoclonal antibody directed against programmed cell death-1, was assessed in patients across multiple tumor types. Development of antidrug antibodies (ADAs) against cemiplimab was monitored using a validated bridging immunoassay. To identify ADA-positive samples in the assay, statistically determined cut points were established by analyzing baseline clinical study samples from a mixed population of different tumor types and this validation cut point was used to assess immunogenicity in all subsequent studies. Regulatory guidance requires that ADA assay cut points be verified for appropriateness in different patient populations. Thus, for the cemiplimab ADA assay, we evaluated whether each new oncology population was comparable to the validation population used to set the cut point. Assay responses from 2393 individual serum samples from 8 different tumor types were compared with the validation population using established statistical methods for cut point determination and comparison, with no significant differences observed. Across tumor types, the immunogenicity of cemiplimab was low, with an overall treatment-emergent ADA incidence rate of 1.9% and 2.5% at intravenous dose regimens of 3 mg/kg every 2 weeks and 350 mg every 3 weeks, respectively. Moreover, no neutralizing antibodies to cemiplimab were detected in patients with ADA-positive samples, and there was no observed impact of cemiplimab ADAs on pharmacokinetics. Study-specific cut points may be required in some diseases such as immune and inflammatory diseases, however, based on this analysis, in-study cut points are not required for each new oncology disease indication for cemiplimab. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.