Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China; Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China.
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Med. 2024 Sep 13;5(9):1150-1163.e3. doi: 10.1016/j.medj.2024.05.009. Epub 2024 Jun 12.
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.
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.
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.
Serplulimab plus HLX04 and XELOX exhibits promising efficacy and is safe and tolerable in patients with treatment-naive mCRC.
This work was funded by Shanghai Henlius Biotech, Inc.
在主要类型的转移性结直肠癌（mCRC）——高度微卫星不稳定性（pMMR）/微卫星稳定（MSS）转移性结直肠癌中，免疫疗法联合当前标准治疗是否能提高疗效尚不清楚。
这是一项 2/3 期试验的随机、双盲、2 期部分，在中国 23 家医院进行（ClinicalTrials.gov：NCT04547166）。招募了无手术切除可能的转移性/复发性结直肠腺癌且无既往全身治疗的患者，以 1:1 的比例随机分配接受每 3 周静脉注射 serplulimab（300mg）加 HLX04（7.5mg/kg）和 XELOX（serplulimab 组）或安慰剂（300mg）加 bevacizumab（7.5mg/kg）和 XELOX（安慰剂组）。主要终点是独立影像学审查委员会（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，共纳入 114 例患者并随机分配至 serplulimab（n=57）或安慰剂（n=57）组。所有患者均患有 IV 期 CRC，95.7%的可评估微卫星不稳定性（MSI）状态的患者为 MSS。中位随访 17.7 个月，serplulimab 组中位 PFS 延长（17.2 个月 vs. 10.7 个月；HR，0.60；95%CI，0.31-1.14）。虽然两组均未达到中位总生存期（OS），但 serplulimab 组 OS 获益趋势明显（HR，0.77；95%CI，0.41-1.45）。serplulimab 和安慰剂组分别有 36（65.5%）和 32（56.1%）例患者发生≥3 级治疗相关不良事件。
在未经治疗的 mCRC 患者中，serplulimab 加 HLX04 和 XELOX 显示出有前景的疗效，且安全耐受。
本工作由上海复宏汉霖生物技术股份有限公司资助。
