Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
J Immunother Cancer. 2020 Jun;8(1). doi: 10.1136/jitc-2019-000437.
Tislelizumab is an investigational, humanized, IgG4 monoclonal antibody with high affinity and binding specificity for programmed cell death-1 (PD-1) that was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy.
The purpose of this phase 1/2, open-label, non-comparative study was to examine the safety, tolerability, and antitumor activity of tislelizumab in adult (≥18 years) Chinese patients with histologically or cytologically confirmed advanced solid tumors with measurable disease. The phase 1 portion of the study consisted of a dose-verification study and a pharmacokinetic (PK) substudy; phase 2 was an indication-expansion study including 11 solid tumor cohorts. Patients previously treated with therapies targeting PD-1 or its ligand, programmed cell death ligand-1 were excluded. During dose-verification, dose-limiting toxicities (DLTs) were monitored; safety and tolerability were examined and the previously determined recommended phase 2 dose (RP2D) was verified. The primary endpoint of phase 2 was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors V.1.1.
As of December 1, 2018, 300 patients were treated with tislelizumab 200 mg intravenously once every 3 weeks (Q3W). Median duration of follow-up was 8.1 months (range 0.2-21.9). No DLTs were reported during the phase 1 dose-verification study and the RP2D was confirmed to be 200 mg intravenously Q3W. Most treatment-related adverse events (62%) were grade 1 or 2, with the most common being anemia (n=70; 23%) and increased aspartate aminotransferase (n=67; 22%). Of the 251 efficacy evaluable patients, 45 (18%) achieved a confirmed clinical response, including one patient from the PK substudy who achieved a complete response. Median duration of response was not reached for all except the nasopharyngeal carcinoma cohort (8.3 months). Antitumor responses were observed in multiple tumor types.
Tislelizumab was generally well tolerated among Chinese patients. Antitumor activity was observed in patients with multiple solid tumors.
CTR20160872.
替雷利珠单抗是一种研究性的、人源化的 IgG4 单克隆抗体，对程序性死亡受体-1（PD-1）具有高亲和力和结合特异性，其被设计为最大限度地减少与巨噬细胞上的 FcγR 的结合，以阻断抗体依赖性吞噬作用，这是 T 细胞清除和潜在对 PD-1 治疗产生耐药的机制。
这项 1/2 期、开放标签、非对照研究的目的是评估替雷利珠单抗在患有经组织学或细胞学证实的晚期实体瘤且有可测量疾病的成年（≥18 岁）中国患者中的安全性、耐受性和抗肿瘤活性。该研究的 1 期部分包括剂量验证研究和药代动力学（PK）子研究；2 期为包括 11 个实体瘤队列的适应症扩展研究。先前接受过针对 PD-1 或其配体程序性死亡配体-1 的治疗的患者被排除在外。在剂量验证期间，监测剂量限制毒性（DLTs）；检查安全性和耐受性，并验证先前确定的 2 期推荐剂量（RP2D）。2 期的主要终点是根据实体瘤反应评估标准 1.1 版（RECIST v1.1）评估的研究者评估的客观缓解率。
截至 2018 年 12 月 1 日，共有 300 名患者接受了替雷利珠单抗 200mg 静脉注射，每 3 周（Q3W）一次。中位随访时间为 8.1 个月（范围 0.2-21.9）。在 1 期剂量验证研究期间未报告 DLTs，并且确认 RP2D 为 200mg 静脉注射 Q3W。大多数与治疗相关的不良事件（62%）为 1 级或 2 级，最常见的是贫血（n=70；23%）和天门冬氨酸氨基转移酶升高（n=67；22%）。在 251 名可评估疗效的患者中，45 名（18%）患者确认临床缓解，包括一名来自 PK 子研究的患者达到完全缓解。除鼻咽癌队列外（8.3 个月），所有患者的缓解持续时间均未达到。在多种肿瘤类型中观察到抗肿瘤反应。
替雷利珠单抗在中国患者中总体耐受性良好。在多种实体瘤患者中观察到抗肿瘤活性。
CTR20160872。
