Suvemcitug plus chemotherapy for platinum-resistant epithelial ovarian, fallopian tube and primary peritoneal cancer: A phase 1b dose-escalation trial

• Published in: Gynecologic oncology Vol. 187; pp. 212 - 220
• Main Authors: Yuan, Guangwen, Zhang, Keqiang, Zheng, Hong, Wu, Yan, Sun, Haolin, Zhang, Jiajing, Sun, Xiyang, Wu, Lingying
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2024
• Subjects: Adult; Aged; Anti-VEGF antibody; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antitumor activities; Carcinoma, Ovarian Epithelial - drug therapy; Dose escalation; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Fallopian Tube Neoplasms - drug therapy; Fallopian Tube Neoplasms - pathology; Female; Hematology, Oncology, and Palliative Medicine; Humans; Middle Aged; Obstetrics and Gynecology; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Peritoneal Neoplasms - drug therapy; Platinum resistance; Progression-Free Survival; Suvemcitug; Topotecan - administration & dosage; Topotecan - adverse effects; Platinum resistance; Anti-VEGF antibody; Dose escalation; Ovarian cancer; Suvemcitug; Antitumor activities
• ISSN: 0090-8258; 1095-6859; 1095-6859
• DOI: 10.1016/j.ygyno.2024.05.005

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. •In this trial, 29 platinum-resistant ovarian cancer patients received escalating doses of suvemcitug plus chemotherapy.•No dose-limiting toxicities occurred and no gastrointestinal perforations were reported.•Nine patients showed investigators-confirmed objective response, with a median progression-free survival of 5.4 months.•The recommended dose for phase 2 study is suvemcitug 1.5 mg/kg every two weeks.•The safety and antitumor activities of suvemcitug support its clinical development for platinum-resistant ovarian cancer.