Liu Yun, Wang Yanfeng, Zhu Yanrong, Wu Tao, Liu Zhenyang, Zhou Jin, Yuan Yuan, Yang Mudan, Liu Bo, Tan Zhenbo, Zhuang Wu, Chen Jiayan, Li Ning, Wang Ying, Hu Xuhui, Wang Lin, Yu Haoyu, Wang Qingyu, Zhu Jun, Huang Jing
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
Cancer Commun (Lond). 2024 Dec;44(12):1431-1443. doi: 10.1002/cac2.12621. Epub 2024 Oct 24.
The combination of anti-PD-1 antibody serplulimab and chemotherapy is considered standard first-line therapy for advanced esophageal squamous cell carcinoma (ESCC), but few later-line treatments are available. Here we evaluated the therapeutic efficacy of the recombinant, humanized anti-EGFR antibody HLX07 when used alone or together with serplulimab and chemotherapy against advanced ESCC.
This open-label, non-randomized, two-cohort, phase 2 trial involved patients 18-75 years old with histologically or cytologically confirmed locally advanced, unresectable, or metastatic ESCC, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients who had failed first-line immuno-chemotherapy or at least two lines of other systemic therapy received HLX07 monotherapy intravenously at a dose of 1,000 mg once every 2 weeks (Q2W). Patients with no prior systemic therapy received HLX07 (1,000 mg, day 1) and serplulimab (200 mg, day 1) intravenously Q2W for up to 2 years, concurrently with cisplatin (50 mg/m, day 1) for up to 8 cycles and 5-fluorouracil (1,200 mg/m, days 1-2) for up to 12 cycles intravenously Q2W. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR).
Overall, 50 patients were enrolled. In the HLX07 monotherapy group, ORR was 15.0% (3/20), and the median PFS was 1.5 months (95% confidence interval [CI], 1.3 to 3.7). The median duration of response was not reached, and the rate of patients showing an objective response lasting at least 6 months was 66.7% (95% CI, 5.4 to 94.5). Two (10.0%, 2/20) patients experienced grade 3-4 treatment-related adverse events (TRAEs), including hypomagnesemia, hypocalcemia, and fatigue. No patient experienced grade 5 TRAEs. In the HLX07 combination group, the ORR was 60.0% (18/30), and the median PFS was 7.8 months (95% CI, 3.3 to 9.1). Fourteen (46.7%, 14/30) patients experienced grade 3-4 TRAEs, and one (3.3%, 1/30) patient died due to serplulimab-related pneumonitis.
HLX07 monotherapy and its combination with serplulimab and chemotherapy showed manageable toxicity and promising antitumor activity in patients with recurrent or metastatic ESCC. Randomized controlled trials are warranted to further establish the safety and efficacy of HLX07 against ESCC.
This trial was registered at Clinicaltrials.gov (NCT05221658).
抗程序性死亡蛋白1（PD-1）抗体斯鲁利单抗与化疗联合应用被认为是晚期食管鳞状细胞癌（ESCC）的标准一线治疗方案，但二线治疗方案有限。在此，我们评估了重组人源化抗表皮生长因子受体（EGFR）抗体HLX07单独使用或与斯鲁利单抗及化疗联合应用治疗晚期ESCC的疗效。
这项开放标签、非随机、双队列2期试验纳入了年龄在18至75岁之间、经组织学或细胞学确诊为局部晚期、不可切除或转移性ESCC且东部肿瘤协作组（ECOG）体能状态为0至1的患者。一线免疫化疗失败或接受过至少两线其他全身治疗的患者接受HLX07单药静脉注射，剂量为1000mg，每2周一次（Q2W）。未接受过全身治疗的患者接受HLX07（1000mg，第1天）和斯鲁利单抗（200mg，第1天）静脉注射Q2W，持续2年，同时联合顺铂（50mg/m²，第1天），最多8个周期，以及5-氟尿嘧啶（1200mg/m²，第1至2天），最多12个周期，静脉注射Q2W。主要终点为无进展生存期（PFS）和客观缓解率（ORR）。
总共纳入了50例患者。在HLX07单药治疗组中，ORR为15.0%（3/20），中位PFS为1.5个月（95%置信区间[CI]，1.3至3.7）。中位缓解持续时间未达到，客观缓解持续至少6个月的患者比例为66.7%（95%CI，5.4至94.5）。2例（10.0%，2/20）患者发生3至4级治疗相关不良事件（TRAEs），包括低镁血症、低钙血症和疲劳。无患者发生5级TRAEs。在HLX07联合治疗组中，ORR为60.0%（18/30），中位PFS为7.8个月（95%CI，3.3至9.1）。14例（46.7%，14/30）患者发生3至4级TRAEs，1例（3.3%，1/30）患者因斯鲁利单抗相关肺炎死亡。
HLX07单药治疗及其与斯鲁利单抗和化疗联合应用在复发或转移性ESCC患者中显示出可管理的毒性和有前景的抗肿瘤活性。有必要开展随机对照试验以进一步确定HLX07治疗ESCC的安全性和有效性。
本试验已在Clinicaltrials.gov注册（NCT05221658）。
