HX008，一种抗 PD1 抗体，联合伊立替康作为二线治疗晚期胃或胃食管结合部癌：一项多中心、单臂 II 期试验。
HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric or gastroesophageal junction cancer: a multicenter, single-arm phase II trial.
机构信息
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, China.
Department of Medical Oncology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
出版信息
J Immunother Cancer. 2020 Oct;8(2). doi: 10.1136/jitc-2020-001279.
BACKGROUND
Irinotecan is used as second-line treatment in advanced gastric or gastroesophageal junction (G/GEJ) cancer. The role of anti-programmed death-1 (PD-1) antibody plus irinotecan, in this setting and population is unclear.
METHODS
This multicenter, open-label, single-arm, phase II trial was conducted in 11 Chinese hospitals. Eligible patients had histologically confirmed advanced G/GEJ cancer that refractory to, or intolerant of, first-line chemotherapy with a platinum and/or fluoropyrimidine. Subjects received HX008 200 mg intravenously every 3 weeks plus irinotecan 160 mg/m intravenously every 2 weeks until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) as assessed according to Response Evaluation Criteria In Solid Tumors V.1.1.
RESULTS
Between October 2018 and September 2019, a total of 58 patients with advanced G/GEJ cancer were enrolled in this study. Median follow-up was 10.5 months (range 7.4-18.9) months. Confirmed ORR was observed in 16 patients, for an ORR of 27.6% (95% CI 16.1% to 39.1%); 19 patients experienced stable disease, leading to a disease control rate of 60.3% (95% CI 46.4% to 73.0%). ORR in patients with PD-ligand 1 (L1) positive (Combined Positive Score (CPS) ≥1) and negative (CPS＜1) tumors was 38.5% (5/13) and 37.5% (3/8), respectively. Median duration of response was 8.0 months (range 1.5-12.5), 6 of 16 (37.5%) responses were ongoing. Median progression-free survival (PFS) was 4.2 months (95% CI 2.2 to 5.5). Median overall survival (OS) was not reached (NR) (95% CI 8.7 to NR). Patients with PD-L1 positive tumors tended to have longer OS than those with PD-L1 negative tumors, but the difference was not statistically significant (NR vs 8.7 months, p=0.1858).The most common treatment-related adverse events of grade 3 or 4 included neutropenia (32.8%), leukopenia (31.0%), anemia (17.2%), decreased appetite (8.6%), vomit (6.9%), nausea (6.9%) and fatigue (5.2%). There were no treatment-related deaths.
CONCLUSION
The combination of HX008 and irinotecan demonstrated promising activity and manageable safety as second-line treatment in patients with advanced G/GEJ cancer, which warrants further study.
TRIAL REGISTRATION NUMBER
NCT03704246.
背景
伊立替康被用作晚期胃或胃食管交界处（G/GEJ）癌症的二线治疗药物。在这种情况下和人群中，抗程序性死亡-1（PD-1）抗体加伊立替康的作用尚不清楚。
方法
这项多中心、开放标签、单臂、二期临床试验在 11 家中国医院进行。符合条件的患者有组织学证实的晚期 G/GEJ 癌症，对一线含铂和/或氟嘧啶化疗不耐受或难治。受试者接受 HX008 200mg 静脉注射，每 3 周 1 次，伊立替康 160mg/m2 静脉注射，每 2 周 1 次，直至疾病进展或出现无法耐受的毒性。主要终点是根据实体瘤反应评估标准 1.1 评估的客观缓解率（ORR）。
结果
2018 年 10 月至 2019 年 9 月，共有 58 名晚期 G/GEJ 癌症患者入组本研究。中位随访时间为 10.5 个月（范围 7.4-18.9）。16 名患者确认缓解，ORR 为 27.6%（95%CI 16.1%至 39.1%）；19 名患者疾病稳定，疾病控制率为 60.3%（95%CI 46.4%至 73.0%）。PD-配体 1（L1）阳性（综合阳性评分（CPS）≥1）和阴性（CPS＜1）肿瘤患者的 ORR 分别为 38.5%（5/13）和 37.5%（3/8）。中位缓解持续时间为 8.0 个月（范围 1.5-12.5），16 名缓解患者中 6 名（37.5%）仍在缓解。中位无进展生存期（PFS）为 4.2 个月（95%CI 2.2 至 5.5）。中位总生存期（OS）未达到（NR）（95%CI 8.7 至 NR）。PD-L1 阳性肿瘤患者的 OS 倾向于长于 PD-L1 阴性肿瘤患者，但差异无统计学意义（NR 与 8.7 个月，p=0.1858）。最常见的 3 级或 4 级治疗相关不良事件包括中性粒细胞减少症（32.8%）、白细胞减少症（31.0%）、贫血（17.2%）、食欲下降（8.6%）、呕吐（6.9%）、恶心（6.9%）和疲劳（5.2%）。无治疗相关死亡。
结论
HX008 联合伊立替康作为晚期 G/GEJ 癌症的二线治疗药物，具有良好的疗效和可管理的安全性，值得进一步研究。
临床试验注册号
NCT03704246。
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