Ning Li, Meng Qiu, Yanqiao Zhang, Mudan Yang, Linzhi Lu, Wei Li, Yuntao Ma, Xiaoming Hou, Guoping Sun, Mingquan Cai, Jingran Wang, Jianwei Lu, Diansheng Zhong, Zhibin Huo, Jingdong Zhang, Xianli Yin, Jun Deng, Zimin Liu, Hongming Pan, Ye Chen, Futang Yang, Haoyu Yu, Jing Li, Qingyu Wang, Jun Zhu, Jin Li
{"title":"HLX22 加曲妥珠单抗生物类似物 HLX02 和 XELOX 作为 HER2 阳性晚期胃癌一线疗法的随机 2 期研究。","authors":"Ning Li, Meng Qiu, Yanqiao Zhang, Mudan Yang, Linzhi Lu, Wei Li, Yuntao Ma, Xiaoming Hou, Guoping Sun, Mingquan Cai, Jingran Wang, Jianwei Lu, Diansheng Zhong, Zhibin Huo, Jingdong Zhang, Xianli Yin, Jun Deng, Zimin Liu, Hongming Pan, Ye Chen, Futang Yang, Haoyu Yu, Jing Li, Qingyu Wang, Jun Zhu, Jin Li","doi":"10.1016/j.medj.2024.06.004","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor.</p><p><strong>Methods: </strong>This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813). Patients with locally advanced/metastatic HER2-positive gastric/gastroesophageal junction cancer and no prior systemic antitumor therapy were randomized 1:1:1 to 25 mg/kg HLX22 (a novel anti-HER2 antibody) + HLX02 (trastuzumab biosimilar) + oxaliplatin and capecitabine (XELOX) (group A), 15 mg/kg HLX22 + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles. Primary endpoints were progression-free survival (PFS) and objective response rate (ORR) assessed by independent radiological review committee (IRRC).</p><p><strong>Findings: </strong>Between November 29, 2021, and June 6, 2022, 82 patients were screened; 53 were randomized to group A (n = 18), B (n = 17), and C (n = 18). With 14.3 months of median follow-up, IRRC-assessed median PFS was prolonged with the addition of HLX22 (A vs. C, 15.1 vs. 8.2 months, hazard ratio [HR] 0.5 [95% confidence interval (CI) 0.17-1.27]; B vs. C, not reached vs. 8.2 months, HR 0.1 [95% CI 0.04-0.52]). Confirmed ORR was comparable among groups (A vs. B vs. C, 77.8% vs. 82.4% vs. 88.9%). Treatment-related adverse events (TRAEs) were observed in 18 (100%), 16 (94.1%), and 17 (94.4%) patients, respectively. One (5.6%) patient in group C reported a grade 5 TRAE.</p><p><strong>Conclusions: </strong>Adding HLX22 to HLX02 and XELOX prolonged PFS and enhanced antitumor response in the first-line treatment of HER2-positive gastric cancer, with manageable safety.</p><p><strong>Funding: </strong>Shanghai Henlius Biotech, Inc.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1255-1265.e2"},"PeriodicalIF":12.8000,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer.\",\"authors\":\"Ning Li, Meng Qiu, Yanqiao Zhang, Mudan Yang, Linzhi Lu, Wei Li, Yuntao Ma, Xiaoming Hou, Guoping Sun, Mingquan Cai, Jingran Wang, Jianwei Lu, Diansheng Zhong, Zhibin Huo, Jingdong Zhang, Xianli Yin, Jun Deng, Zimin Liu, Hongming Pan, Ye Chen, Futang Yang, Haoyu Yu, Jing Li, Qingyu Wang, Jun Zhu, Jin Li\",\"doi\":\"10.1016/j.medj.2024.06.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor.</p><p><strong>Methods: </strong>This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813). Patients with locally advanced/metastatic HER2-positive gastric/gastroesophageal junction cancer and no prior systemic antitumor therapy were randomized 1:1:1 to 25 mg/kg HLX22 (a novel anti-HER2 antibody) + HLX02 (trastuzumab biosimilar) + oxaliplatin and capecitabine (XELOX) (group A), 15 mg/kg HLX22 + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles. Primary endpoints were progression-free survival (PFS) and objective response rate (ORR) assessed by independent radiological review committee (IRRC).</p><p><strong>Findings: </strong>Between November 29, 2021, and June 6, 2022, 82 patients were screened; 53 were randomized to group A (n = 18), B (n = 17), and C (n = 18). With 14.3 months of median follow-up, IRRC-assessed median PFS was prolonged with the addition of HLX22 (A vs. C, 15.1 vs. 8.2 months, hazard ratio [HR] 0.5 [95% confidence interval (CI) 0.17-1.27]; B vs. C, not reached vs. 8.2 months, HR 0.1 [95% CI 0.04-0.52]). 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引用次数: 0
摘要
背景：胃癌是全球第五大常见癌症，也是第四大常见死亡原因：胃癌是全球第五大常见癌症和第四大常见癌症死因，但晚期疾病的预后仍然很差：这是一项随机、双盲、2 期试验（ClinicalTrials.gov：NCT04908813）。局部晚期/转移性 HER2 阳性胃癌/胃食管交界处癌患者，既往未接受过全身抗肿瘤治疗者，按 1:1 随机分配：1至25 mg/kg HLX22（一种新型抗HER2抗体）+HLX02（曲妥珠单抗生物类似物）+奥沙利铂和卡培他滨（XELOX）（A组）、15 mg/kg HLX22 + HLX02 + XELOX（B组）或安慰剂 + HLX02 + XELOX（C组），3周为一个周期。主要终点是由独立放射学审查委员会（IRRC）评估的无进展生存期（PFS）和客观反应率（ORR）：2021年11月29日至2022年6月6日期间，共筛选出82名患者；53名患者被随机分配到A组（18人）、B组（17人）和C组（18人）。中位随访时间为14.3个月，IRRC评估的中位PFS在添加HLX22后有所延长（A组与C组相比，分别为15.1个月与8.2个月，危险比[HR]为0.5[95%置信区间（CI）为0.17-1.27]；B组与C组相比，分别为8.2个月与8.1个月，危险比为0.1[95%置信区间（CI）为0.04-0.52]）。各组的确诊 ORR 相当（A 组 vs. B 组 vs. C 组，77.8% vs. 82.4% vs. 88.9%）。分别有 18 例（100%）、16 例（94.1%）和 17 例（94.4%）患者出现治疗相关不良事件（TRAEs）。C组有一名（5.6%）患者报告了5级TRAE：结论：在HLX02和XELOX基础上添加HLX22可延长HER2阳性胃癌一线治疗的PFS，增强抗肿瘤反应，且安全性可控：上海恒流生物技术有限公司
A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer.
Background: Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor.
Methods: This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813). Patients with locally advanced/metastatic HER2-positive gastric/gastroesophageal junction cancer and no prior systemic antitumor therapy were randomized 1:1:1 to 25 mg/kg HLX22 (a novel anti-HER2 antibody) + HLX02 (trastuzumab biosimilar) + oxaliplatin and capecitabine (XELOX) (group A), 15 mg/kg HLX22 + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles. Primary endpoints were progression-free survival (PFS) and objective response rate (ORR) assessed by independent radiological review committee (IRRC).
Findings: Between November 29, 2021, and June 6, 2022, 82 patients were screened; 53 were randomized to group A (n = 18), B (n = 17), and C (n = 18). With 14.3 months of median follow-up, IRRC-assessed median PFS was prolonged with the addition of HLX22 (A vs. C, 15.1 vs. 8.2 months, hazard ratio [HR] 0.5 [95% confidence interval (CI) 0.17-1.27]; B vs. C, not reached vs. 8.2 months, HR 0.1 [95% CI 0.04-0.52]). Confirmed ORR was comparable among groups (A vs. B vs. C, 77.8% vs. 82.4% vs. 88.9%). Treatment-related adverse events (TRAEs) were observed in 18 (100%), 16 (94.1%), and 17 (94.4%) patients, respectively. One (5.6%) patient in group C reported a grade 5 TRAE.
Conclusions: Adding HLX22 to HLX02 and XELOX prolonged PFS and enhanced antitumor response in the first-line treatment of HER2-positive gastric cancer, with manageable safety.
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.
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