IBI310 plus sintilimab vs. placebo plus sintilimab in recurrent/metastatic cervical cancer: A double-blind, randomized controlled trial.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2025-01-15 DOI:10.1016/j.medj.2024.100573

Huayi Li, Yu Xu, Xiaofei Jiao, Qin Xu, Zikun Peng, Ying Tang, Jieqing Zhang, Bowen Huang, Yiyang Shen, Baoping Chang, Bairong Xia, Wei Duan, Danbo Wang, Lijing Zhu, Ruifang An, Guonan Zhang, Yaling Tang, Jianli Huang, Hui Qiu, Li Wang, Yi Huang, Guiling Li, Jianhua Qian, Li Sun, Hong Zheng, Ge Lou, Youzhong Zhang, Youguo Chen, Liqin Lu, Yan Cheng, Jihong Liu, Weidong Zhao, Jianghai Ji, Aiqin He, Ke Wang, Guohua Yu, Hong Zhu, Cailing Ma, Jianlin Yuan, Xia Wang, Hongfei Zhang, Xinyan Ma, Chujun Cai, Kang Yin, Han Xie, Ya Wang, Shuyan Wang, Li Li, Hui Zhou, Jing Wang, Jianqing Zhu, Ding Ma, Qinglei Gao

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引用次数: 0

Abstract

Background: It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC).

Methods: In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3 weeks for 12 weeks, followed by sintilimab alone. The primary endpoint was the objective response rate (ORR). Pivotal secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.

Findings: 205 patients were randomized to receive IBI310-sintilimab (n = 103) or placebo-sintilimab (n = 102). The ORR difference between the IBI310-sintilimab arm (32.3%, 95% confidence interval [CI]: 23.3%-42.5%) and the placebo-sintilimab arm (23.5%, 95% CI: 15.5%-33.1%) was not significant (p = 0.17). IBI310-sintilimab and placebo-sintilimab exhibited median PFS values of 3.6 (95% CI: 2.7-6.3) and 4.2 months (95% CI: 2.8-6.2), respectively (hazard ratio [HR] = 0.91, 95% CI: 0.65-1.27; p = 0.58). The median OSs were 13.9 months (95% CI: 11.5-25.6) in the IBI310-sintilimab arm and 17.2 months (95% CI: 13.7-25.9) in the placebo-sintilimab arm (HR = 1.12, 95% CI: 0.79-1.58; p = 0.54). Adding IBI310 to sintilimab increased the incidence of grade ≥3 treatment-related adverse events (55% versus 19%).

Conclusions: Compared to single-agent PD-1/PD-L1 blockade, dual blockade of CTLA-4 and PD-1/PD-L1 did not significantly improve clinical outcomes in R/M CC.

Funding: This work was funded by Innovent Biologics (Suzhou).

查看原文本刊更多论文

IBI310加辛替单抗与安慰剂加辛替单抗治疗复发/转移性宫颈癌：一项双盲、随机对照试验

背景：目前尚不清楚在PD-1/PD-L1阻断的基础上加入CTLA-4阻断是否能改善宫颈癌（CC）的临床结局。方法：在这项随机、双盲、安慰剂对照的2期研究中（ClinicalTrials.gov）：NCT04590599)，在铂基化疗后或期间经历疾病进展的复发/转移性CC （R/M CC）患者从中国37个中心入组，随机分配（1:1），按PD-L1表达和既往治疗线分层，接受IBI310加辛替单抗或安慰剂加辛替单抗静脉注射，每3周一次，持续12周，随后单独使用辛替单抗。主要终点为客观缓解率（ORR）。关键次要终点包括无进展生存期（PFS）、总生存期（OS）和安全性。结果：205例患者被随机分为ibi310 -辛替单抗组（n = 103）和安慰剂-辛替单抗组（n = 102）。ibi310 -辛替单抗组（32.3%，95%可信区间[CI]: 23.3%-42.5%）与安慰剂-辛替单抗组（23.5%,95% CI: 15.5%-33.1%）的ORR差异无统计学意义（p = 0.17）。ibi310 -辛替单抗和安慰剂-辛替单抗的中位PFS值分别为3.6个月（95% CI: 2.7-6.3）和4.2个月（95% CI: 2.8-6.2）(风险比[HR] = 0.91, 95% CI: 0.65-1.27；P = 0.58)。ibi310 -辛替单抗组的中位生存期为13.9个月（95% CI: 11.5-25.6），安慰剂-辛替单抗组的中位生存期为17.2个月（95% CI: 13.7-25.9） (HR = 1.12, 95% CI: 0.79-1.58；P = 0.54)。在辛替单抗中加入IBI310增加了≥3级治疗相关不良事件的发生率（55%对19%）。结论：与单药PD-1/PD-L1阻断相比，CTLA-4和PD-1/PD-L1的双重阻断并没有显著改善R/M cc的临床结果。资助：本研究由创新生物（苏州）公司资助。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

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