索卡佐利单抗用于既往治疗失败的晚期尿路上皮癌的Ⅰ期临床研究  

A phase Ⅰ study of socazolimab for previously treated advanced urothelial carcinoma patients

作　　者：唐碧霞[1] 段荣 李思明[2] 盛锡楠[2] 崔传亮[2] 斯璐[1] 鄢谢桥 周莉[2] 毛丽丽[1] 连斌[1] 王轩[1] 白雪[1] 许华艳 李彩莉 李小羿 戴向荣 迟志宏[1] 郭军[2] TANG Bi-xia;DUAN Rong;LI Si-ming;SHENG Xi-nan;CUI Chuan-liang;SI Lu;YAN Xie-qiao;ZHOU Li;MAO Li-li;LIAN Bin;WANG Xuan;BAI Xue;XU Hua-yan;LI Cai-li;LI Xiao-yi;DAI Xiang-rong;CHIZhi-hong;GUO Jun(Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Melanoma and Sarcoma Oncology,Department of Genitourinary Oncology,Peking University Cancer Hospital&Institute,BEIJING 100142,China;Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Genitourinary Oncology,Peking University Cancer Hospital&Institute,BEIJING 100142,China;Zhaoke(Guangzhou)Oncology Pharmaceutical Limited,Guangzhou GUANGDONG 511462,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所黑色素瘤与肉瘤内科,恶性肿瘤发病机制及转移研究教育部重点实验室,北京100142 [2]北京大学肿瘤医院暨北京市肿瘤防治研究所泌尿肿瘤内科,恶性肿瘤发病机制及转移研究教育部重点实验室,北京100142 [3]兆科(广州)肿瘤药物有限公司,广东广州511462

出　　处：《中国新药与临床杂志》2022年第12期748-753,共6页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的评估索卡佐利单抗单药治疗中国晚期尿路上皮癌患者的安全性和耐受性,并初步观察其疗效。方法纳入标准方案治疗失败的尿路上皮癌晚期患者10例,依次进入3个不同剂量组,接受索卡佐利单抗(5、10、15 mg·kg^(-1),静脉滴注,每14 d为一个治疗周期)单药治疗,按“3+3”模式进行剂量递增。观察患者剂量限制性毒性(DLT)和最大耐受剂量(MTD),并明确Ⅱ期临床试验推荐剂量,记录治疗相关不良事件(TRAE)。治疗期间每8周进行影像学疗效评估,并进行患者生存分析。结果所有患者均未发生DLT反应,未观察到MTD,Ⅱ期临床试验推荐剂量为5 mg·kg^(-1)。常见的TRAE包括高血糖症(4/10)、血肌酸磷酸激酶升高(4/10)、皮疹(2/10)、白细胞计数降低(2/10)等。客观缓解率为30%(95%CI:6.7%~65.2%),中位无进展生存期为2.66个月(95%CI:2.56~29.14个月),中位总生存期为15.47个月(95%CI:6.97~29.14个月)。结论索卡佐利单抗在中国人群中总体耐受性良好,且单药治疗晚期尿路上皮癌有较好的临床疗效,可进一步探索联合治疗在尿路上皮癌治疗中的应用。AIM To evaluate the safety and tolerability of socazolimab in the treatment of advanced urothelial carcinoma in China,and preliminarily observe the curative effect.METHODS Ten patients with advanced urothelial carcinoma who failed with the standard regimen were enrolled in three different dose groups and received single drug therapy of socazolimab(5,10,15 mg·kg^(-1),intravenous drip,every 14 days as a treatment cycle),and the dose was increased according to the“3+3”mode.The dose limiting toxicity(DLT)and maximum tolerated dose(MTD)were observed,the recommended dose in phase Ⅱ clinical trial was determined,and treatment related adverse events(TRAE)were recorded.The efficacy was evaluated according to the imaging examination every 8 weeks during the treatment,and the survival of patients were analyzed.RESULTS All patients were evaluable for safety,and no DLT reaction occurred,no MTD was observed.The recommended dose for phase Ⅱ was 5 mg·kg^(-1).The common TRAE were hyperglycemia(4/10),elevated serum creatine phosphokinase(4/10),rash(2/10),and decreased leukocyte count(2/10),etc.The objective response rate was 30%(95%CI:6.7%to 65.2%),the median progression free survival was 2.66 months(95%CI:2.56 to 29.14months),and the median overall survival was 15.47 months(95%CI:6.97 to 29.14 months).CONCLUSION Socazolimab is demonstrated a manageable safety profile and evidence of meaningful clinical activity separately in the Chinese patients with advanced urothelial carcinoma.The application of combined therapy in the treatment of urothelial carcinoma can be further explored.

关 键 词：索卡佐利单抗 泌尿系肿瘤 免疫检查点抑制剂 临床试验 Ⅰ期 程序性死亡受体配体1 

分 类 号：R737.1[医药卫生—肿瘤] R979.19[医药卫生—临床医学]