First-line serplulimab in metastatic colorectal cancer: Phase 2 results of a randomized, double-blind, phase 2/3 trial.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2024-09-13 Epub Date: 2024-06-12 DOI:10.1016/j.medj.2024.05.009

Zi-Xian Wang, Junjie Peng, Xinjun Liang, Ying Cheng, Yanhong Deng, Kehe Chen, Mingjun Zhang, Jingdong Zhang, Wei Wang, Bangwei Cao, Yongdong Jin, Meili Sun, Yuan Lin, Suxia Luo, Zhen Li, Liu Yang, Ying Ke, Haoyu Yu, Jing Li, Qingyu Wang, Jun Zhu, Feng Wang, Rui-Hua Xu

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引用次数: 0

Abstract

Background: Whether or not the addition of immunotherapy to current standard-of-care treatments can improve efficacy in proficient mismatch repair (pMMR)/microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), the predominant type of mCRC, is unclear.

Methods: This randomized, double-blind, phase 2 part of a phase 2/3 trial was conducted at 23 hospitals across China (ClinicalTrials.gov: NCT04547166). Patients with unresectable metastatic/recurrent colorectal adenocarcinoma and no prior systemic therapy were randomly assigned 1:1 to receive every-3-weeks intravenous serplulimab (300 mg) plus HLX04 (7.5 mg/kg) and XELOX (serplulimab group) or placebo (300 mg) plus bevacizumab (7.5 mg/kg) and XELOX (placebo group). The primary endpoint was independent radiology review committee (IRRC)-assessed progression-free survival (PFS). Secondary endpoints included other efficacy endpoints and safety.

Findings: Between July 16, 2021, and January 20, 2022, 114 patients were enrolled and randomly assigned to the serplulimab (n = 57) or placebo (n = 57) group. All patients had stage IV CRC, and 95.7% of the patients with available microsatellite instability (MSI) status were MSS. With a median follow-up duration of 17.7 months, median PFS was prolonged in the serplulimab group (17.2 vs. 10.7 months; hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.31-1.14). Although the median overall survival (OS) was not reached for either group, a trend of an OS benefit was observed for the serplulimab group (HR, 0.77; 95% CI, 0.41-1.45). 36 (65.5%) and 32 (56.1%) patients in the serplulimab and placebo groups had grade ≥3 treatment-related adverse events, respectively.

Conclusions: Serplulimab plus HLX04 and XELOX exhibits promising efficacy and is safe and tolerable in patients with treatment-naive mCRC.

Funding: This work was funded by Shanghai Henlius Biotech, Inc.

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转移性结直肠癌的一线舍普利单抗：随机、双盲、2/3 期试验的第 2 阶段结果。

背景：在目前的标准治疗方法中加入免疫疗法能否提高精通错配修复（pMMR）/微卫星稳定（MSS）转移性结直肠癌（mCRC）（mCRC的主要类型）的疗效尚不清楚：这项随机、双盲、2/3期试验的第2期在全国23家医院进行（ClinicalTrials.gov：NCT04547166）。患有不可切除的转移性/复发性结直肠腺癌且之前未接受过系统治疗的患者被1:1随机分配到每3周静脉注射一次舍鲁单抗（300毫克）加HLX04（7.5毫克/千克）和XELOX（舍鲁单抗组）或安慰剂（300毫克）加贝伐单抗（7.5毫克/千克）和XELOX（安慰剂组）。主要终点是独立放射学审查委员会（IRRC）评估的无进展生存期（PFS）。次要终点包括其他疗效终点和安全性：2021年7月16日至2022年1月20日期间，114名患者入组并被随机分配到serplulimab组（n = 57）或安慰剂组（n = 57）。所有患者均为IV期CRC，95.7%的患者具有微卫星不稳定性（MSI）状态。中位随访时间为17.7个月，Serplulimab组的中位PFS延长（17.2个月对10.7个月；危险比[HR]，0.60；95%置信区间[CI]，0.31-1.14）。虽然两组患者的中位总生存期（OS）均未达到，但观察到丝普利单抗组在OS方面有获益的趋势（HR，0.77；95% CI，0.41-1.45）。Serplulimab组和安慰剂组分别有36例（65.5%）和32例（56.1%）患者出现≥3级治疗相关不良事件：结论：Serplulimab联合HLX04和XELOX对治疗无效的mCRC患者具有良好的疗效、安全性和耐受性：本研究由上海恒流生物技术有限公司资助。

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

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.