MD Anderson Cancer Center, Houston, Texas, USA
Massachusetts General Hospital, Boston, Massachusetts, USA.
J Immunother Cancer. 2020 Mar;8(1). doi: 10.1136/jitc-2020-000530.
Spartalizumab is a humanized IgG4κ monoclonal antibody that binds programmed death-1 (PD-1) and blocks its interaction with PD-L1 and PD-L2. This phase 1/2 study was designed to assess the safety, pharmacokinetics, and preliminary efficacy of spartalizumab in patients with advanced or metastatic solid tumors.
In the phase 1 part of the study, 58 patients received spartalizumab, intravenously, at doses of 1, 3, or 10 mg/kg, administered every 2 weeks (Q2W), or 3 or 5 mg/kg every 4 weeks (Q4W).
Patients had a wide range of tumor types, most commonly sarcoma (28%) and metastatic renal cell carcinoma (10%); other tumor types were reported in ≤3 patients each. Most patients (93%) had received prior antineoplastic therapy (median three prior lines) and two-thirds of the population had tumor biopsies negative for PD-L1 expression at baseline. The maximum tolerated dose was not reached. The recommended phase 2 doses were selected as 400 mg Q4W or 300 mg Q3W. No dose-limiting toxicities were observed, and adverse events included those typical of other PD-1 antibodies. The most common treatment-related adverse events of any grade were fatigue (22%), diarrhea (17%), pruritus (14%), hypothyroidism (10%), and nausea (10%). Partial responses occurred in two patients (response rate 3.4%); one with atypical carcinoid tumor of the lung and one with anal cancer. Paired tumor biopsies from patients taken at baseline and on treatment suggested an on-treatment increase in CD8+ lymphocyte infiltration in patients with clinical benefit.
Spartalizumab was well tolerated at all doses tested in patients with previously treated advanced solid tumors. On-treatment immune activation was seen in tumor biopsies; however, limited clinical activity was reported in this heavily pretreated, heterogeneous population. The phase 2 part of this study is ongoing in select tumor types.
NCT02404441.
Spartalizumab 是一种人源化 IgG4κ 单克隆抗体，可与程序性死亡受体-1（PD-1）结合并阻断其与 PD-L1 和 PD-L2 的相互作用。这项 1/2 期研究旨在评估 Spartalizumab 在晚期或转移性实体瘤患者中的安全性、药代动力学和初步疗效。
在研究的 1 期部分，58 名患者接受 Spartalizumab 静脉输注，剂量为 1、3 或 10mg/kg，每 2 周（Q2W）给药，或 3 或 5mg/kg 每 4 周（Q4W）给药。
患者的肿瘤类型广泛，最常见的是肉瘤（28%）和转移性肾细胞癌（10%）；其他肿瘤类型各报告了≤3 例。大多数患者（93%）接受过抗肿瘤治疗（中位数为三线治疗），三分之二的患者在基线时肿瘤活检 PD-L1 表达阴性。未达到最大耐受剂量。选定的 2 期推荐剂量为 400mg Q4W 或 300mg Q3W。未观察到剂量限制毒性，不良事件包括其他 PD-1 抗体的典型不良事件。任何级别最常见的治疗相关不良事件是疲劳（22%）、腹泻（17%）、瘙痒（14%）、甲状腺功能减退（10%）和恶心（10%）。两名患者（反应率 3.4%）出现部分缓解，其中一名患有非典型类癌肺肿瘤，另一名患有肛门癌。对基线和治疗期间接受治疗的患者进行配对肿瘤活检表明，在有临床获益的患者中，治疗期间 CD8+淋巴细胞浸润增加。
Spartalizumab 在所有测试剂量下均耐受良好，用于治疗先前接受过治疗的晚期实体瘤患者。在肿瘤活检中观察到治疗相关的免疫激活；然而，在这个预处理广泛、异质性的人群中，报告的临床活性有限。该研究的 2 期部分正在选定的肿瘤类型中进行。
NCT02404441。
