An Jusheng, Tang Jie, Li Benjamin X, Xiong Huihua, Qiu Hui, Luo Lin, Wang Li, Wang Danbo, Zhou Qi, Xu Qin, Song Honglin, Zhang Yunyan, Zhang Hongping, Li Yujie, Yu Xiaohui, Zhang Jing, Ng Rachel, Zhao Wayne, Wong Michael, Dai Xiangrong, Li Guiling, Wu Lingying
Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Hunan Tumor Hospital, Hunan, China.
Clin Cancer Res. 2022 Dec 1;28(23):5098-5106. doi: 10.1158/1078-0432.CCR-22-1280.
This study (ClinicalTrials.gov identifier, NCT03676959) is an open, phase I dose-escalation and expansion study investigating the safety and efficacy of the recombinant, fully human anti-programmed death ligand 1 (PD-L1) mAb socazolimab in patients diagnosed with recurrent or metastatic cervical cancer.
Patients received socazolimab every 2 weeks until disease progression. The study was divided into a dose-escalation phase and a dose-expansion phase. Safety and tolerability were primary endpoints of the dose-escalation phase. The primary endpoints of the dose-expansion phase were safety and the objective response rate (ORR) of the 5 mg/kg dose. Efficacy was assessed by the third-party independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
104 patients were successfully enrolled into the study. Twelve patients were included in the dose-escalation phase, with one complete response and two partial responses in the 5 mg/kg treatment group. Ninety-two patients (5 mg/kg) were enrolled in the dose-expansion phase. Fifty-four patients (59.3%) had baseline PD-L1-positive tumor expression (combined positive score ≥1). ORR was 15.4% [95% confidence interval (CI), 8.7%-24.5%]. Median PFS was 4.44 months (95% CI, 2.37-5.75 months), and the median OS was 14.72 months (95% CI, 9.59-NE months). ORR of PD-L1-positive patients was 16.7%, and the ORR of PD-L1-negative patients was 17.9%. No treatment-related deaths occurred.
Our study demonstrates that socazolimab has durable safety and efficacy for the treatment of recurrent or metastatic cervical cancer and exhibits a safety profile similar to other anti-PD-1/PD-L1 mAbs.
本研究（ClinicalTrials.gov标识符，NCT03676959）是一项开放的I期剂量递增和扩展研究，旨在调查重组全人源抗程序性死亡配体1（PD-L1）单克隆抗体索卡唑单抗在诊断为复发性或转移性宫颈癌患者中的安全性和有效性。
患者每2周接受一次索卡唑单抗治疗，直至疾病进展。该研究分为剂量递增阶段和剂量扩展阶段。安全性和耐受性是剂量递增阶段的主要终点。剂量扩展阶段的主要终点是安全性和5mg/kg剂量的客观缓解率（ORR）。疗效由第三方独立审查委员会（IRC）根据实体瘤疗效评价标准1.1版（RECIST 1.1）进行评估。
104例患者成功入组本研究。12例患者纳入剂量递增阶段，5mg/kg治疗组有1例完全缓解和2例部分缓解。92例患者（5mg/kg）纳入剂量扩展阶段。54例患者（59.3%）基线时PD-L1肿瘤表达阳性（联合阳性评分≥1）。ORR为15.4%[95%置信区间（CI），8.7%-24.5%]。中位无进展生存期为4.44个月（95%CI，2.37-5.75个月），中位总生存期为14.72个月（95%CI，9.59-NE个月）。PD-L1阳性患者的ORR为16.7%，PD-L1阴性患者的ORR为17.9%。未发生与治疗相关的死亡。
我们的研究表明，索卡唑单抗在治疗复发性或转移性宫颈癌方面具有持久的安全性和有效性，并且其安全性与其他抗PD-1/PD-L1单克隆抗体相似。
