Abstract：
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.
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.
摘要：
目的：尽管在铂类耐药的卵巢癌患者中具有明显的无进展生存期（PFS）获益，但由于安全性问题，贝伐单抗的使用受到阻碍。强调了对新型有效和安全的抗血管生成药物的需求。本研究旨在表征耐受性，安全,在铂耐药的卵巢癌患者中，递增剂量的抗VEGF抗体suvemcitug加化疗的抗肿瘤活性。
方法：这个开放标签，剂量递增试验纳入了经组织学或细胞学证实的铂耐药上皮性卵巢的成年患者（≥18岁），输卵管和原发性腹膜癌。符合条件的患者每两周接受一次紫杉醇或托泊替康以及递增剂量的suvemcitug0.5、1、1.5或2mg/kg。主要终点是安全性和耐受性，和suvemcitug的抗肿瘤活性。
结果：29名受试者接受了紫杉醇（n=11）或拓扑替康（n=18）。没有发生剂量限制性毒性。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%)。无胃肠道穿孔发生。9名受试者(31.0%，95%CI15.3-50.8)证明了研究者确认的客观反应，包括1的完全反应和8的部分反应。中位PFS为5.4个月（95%CI2.2-7.4）。
结论：Suvemcitug在铂耐药的卵巢癌患者中显示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发展。
方法：这个开放标签，剂量递增试验纳入了经组织学或细胞学证实的铂耐药上皮性卵巢的成年患者（≥18岁），输卵管和原发性腹膜癌。符合条件的患者每两周接受一次紫杉醇或托泊替康以及递增剂量的suvemcitug0.5、1、1.5或2mg/kg。主要终点是安全性和耐受性，和suvemcitug的抗肿瘤活性。
结果：29名受试者接受了紫杉醇（n=11）或拓扑替康（n=18）。没有发生剂量限制性毒性。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%)。无胃肠道穿孔发生。9名受试者(31.0%，95%CI15.3-50.8)证明了研究者确认的客观反应，包括1的完全反应和8的部分反应。中位PFS为5.4个月（95%CI2.2-7.4）。
结论：Suvemcitug在铂耐药的卵巢癌患者中显示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发展。
