Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California.
Division of Hematology/Clinical Oncology, University of Alabama at Birmingham, Birmingham, Alabama.
Cancer. 2019 Apr 1;125(7):1124-1132. doi: 10.1002/cncr.31912. Epub 2019 Jan 9.
Cluster of differentiation 70 (CD70) is frequently expressed in renal cell carcinoma (RCC) and has immunomodulatory properties. An antibody-drug conjugate targeting CD70, SGN-CD70A, was developed to treat patients with CD70-positive RCC.
The objective of this phase 1, open-label, dose-escalation, multicenter study was to evaluate the safety and tolerability of SGN-CD70A and establish its maximum tolerated dose in patients with CD70-positive, metastatic RCC (mRCC). All subtypes of RCC were permitted, and no limit was set on the number of prior therapies. Safety assessments consisted of monitoring and recording all adverse events (AEs) and dose-limiting toxicities (DLTs). Treatment response was assessed by radiographic tumor evaluation according to the Response Evaluation Criteria for Solid Tumors, version 1.1. A model-based, modified continual-reassessment method was used to estimate the probabilities of DLT and response.
The maximum tolerated dose was determined to be 30 μg/kg, with thrombocytopenia as the DLT. The most common AEs were fatigue (67%), anemia (61%), and thrombocytopenia (56%). Of 18 enrolled patients, 1 achieved a partial response and 13 achieved stable disease, for a clinical benefit rate of 78%. Limitations of the study included the heavily pretreated nature of patients, receipt of a median of 4 prior lines of therapy (range, 1-8 prior lines of therapy), and diminishing response potential.
The modest antitumor activity of SGN-CD70A does not support its development in mRCC. However, given the high disease control rate in a heavily pretreated population and the modest toxicity profile, CD70 remains of interest because of its immunomodulatory properties.
分化抗原 70（CD70）在肾细胞癌（RCC）中经常表达，并具有免疫调节特性。一种针对 CD70 的抗体药物偶联物 SGN-CD70A 被开发出来用于治疗 CD70 阳性的 RCC 患者。
这项 1 期、开放标签、剂量递增、多中心研究的目的是评估 SGN-CD70A 的安全性和耐受性，并确定其在 CD70 阳性转移性 RCC（mRCC）患者中的最大耐受剂量。允许所有 RCC 亚型入组，且对既往治疗的次数没有限制。安全性评估包括监测和记录所有不良事件（AE）和剂量限制性毒性（DLT）。根据实体瘤反应评估标准 1.1 版进行影像学肿瘤评估来评估治疗反应。采用基于模型的改良连续再评估方法来估计 DLT 和反应的概率。
确定 30μg/kg 为最大耐受剂量，血小板减少症为 DLT。最常见的 AE 是疲劳（67%）、贫血（61%）和血小板减少症（56%）。在 18 名入组患者中，1 名患者达到部分缓解，13 名患者达到疾病稳定，临床获益率为 78%。研究的局限性包括患者既往治疗的程度较重，中位数接受了 4 线治疗（范围为 1-8 线治疗），以及潜在反应能力降低。
SGN-CD70A 的抗肿瘤活性适度，不支持其在 mRCC 中的开发。然而，鉴于在既往治疗程度较重的患者中疾病控制率较高，且毒性谱适度，CD70 因其免疫调节特性仍然具有研究价值。
