Gynecologic Oncology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Gynecology and Oncology Ward V, Hunan Cancer Hospital, No. 283 Tongzipo Road, Yuelu District, Changsha, Hunan Province, China.
Gynecol Oncol. 2024 Aug;187:212-220. doi: 10.1016/j.ygyno.2024.05.005. Epub 2024 May 27.
The use of bevacizumab has been hampered by safety concerns despite demonstrable progression-free survival (PFS) benefit in subjects with platinum-resistant ovarian cancer, highlighting the need for novel effective and safe antiangiogenic agents. This study aimed to characterize the tolerability, safety, and antitumor activities of escalating doses of anti-VEGF antibody suvemcitug plus chemotherapy in platinum-resistant ovarian cancer patients.
This open-label, dose-escalation trial enrolled adult patients (≥18 years) with platinum-resistant histologically or cytologically-confirmed epithelial ovarian, fallopian tube and primary peritoneal cancer. Eligible patients received paclitaxel or topotecan plus escalating doses of suvemcitug 0.5, 1, 1.5, or 2 mg/kg once every two weeks. The primary endpoints were safety and tolerability, and antitumor activities of suvemcitug.
Twenty-nine subjects received paclitaxel (n = 11) or topotecan (n = 18). No dose-limiting toxicities occurred. The most common adverse events of special interest were proteinuria (41.4%), hypertension (20.7%) and epistaxis (10.3%). No gastrointestinal perforations occurred. Nine subjects (31.0%, 95% CI 15.3-50.8) demonstrated investigators-confirmed objective response, including complete response in 1 and partial response in 8. The median PFS was 5.4 months (95% CI 2.2-7.4).
Suvemcitug demonstrated an acceptable safety profile and promising antitumor activities in platinum-resistant ovarian cancer patients, supporting its further clinical development.
贝伐单抗的应用受到安全性问题的阻碍，尽管在铂耐药卵巢癌患者中显示出无进展生存期（PFS）获益，这凸显了对新型有效和安全的抗血管生成药物的需求。本研究旨在描述抗 VEGF 抗体苏维木单抗联合化疗治疗铂耐药卵巢癌患者的耐受性、安全性和抗肿瘤活性。
这项开放标签、剂量递增的临床试验纳入了成年患者（≥18 岁），这些患者患有铂耐药的组织学或细胞学证实的上皮性卵巢癌、输卵管癌和原发性腹膜癌。符合条件的患者接受紫杉醇或拓扑替康联合苏维木单抗递增剂量 0.5、1、1.5 或 2mg/kg，每两周一次。主要终点是苏维木单抗的安全性和耐受性以及抗肿瘤活性。
29 名患者接受了紫杉醇（n=11）或拓扑替康（n=18）治疗。未发生剂量限制毒性。最常见的特别关注的不良事件是蛋白尿（41.4%）、高血压（20.7%）和鼻出血（10.3%）。未发生胃肠道穿孔。9 名患者（31.0%，95%CI 15.3-50.8）表现出研究者确认的客观缓解，包括 1 例完全缓解和 8 例部分缓解。中位 PFS 为 5.4 个月（95%CI 2.2-7.4）。
苏维木单抗在铂耐药卵巢癌患者中表现出可接受的安全性和有希望的抗肿瘤活性，支持其进一步的临床开发。
