Efficacy and safety of Geptanolimab in previously treated PD-L1-Positive recurrent or metastatic cervical cancer: a multi-center openlabel, single-arm, phase Ⅱ study

Jusheng An ^1,2 Mei Feng ³ Ke-Qiang Zhang ⁴ Jianqing Zhu ⁵ Aiqin He ⁶ Xiumin Li ⁷ Jin Peng ⁸ Xinwen Wang ⁹ Hongping Zhang ¹⁰ Weimin Kong ¹¹ Guiling Li ¹² Jianlin Yuan ¹³ Hu Liu ¹⁴ Yueyin Pan ¹⁴ Shiying Yu ¹⁵ Liangfang Shen ¹⁶ Hong Zhu ¹⁶ Cailing Ma ¹⁷ Hongmin Chen ¹⁸ Min Hao ¹⁹ Wenjun Cheng ²⁰ Wenxue Zhang ²¹ Chao Deng ²² Chunhong Hu ²³ Yi Huang ²⁴ Jian Zhang ²⁵ Kairong Huang ²⁶ Zhijie Liu ²⁷ Zhaofeng Zhu ²⁸ Fan Xie ²⁹ Yunyan Zhang ^30* Lingying Wu ^2*

• ¹ Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, China
• ² Department of Gynecologic Oncology, National Cancer Centre/ National Clinical Research Centre for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College., Beijing, China
• ³ Department of Gynecology, Clinical Oncology School of Fujian Medical University，Fujian Cancer Hospital, Fuzhou, China
• ⁴ Gynecologic Oncology, The Affiliated Cancer of Xiangya School of Medicine, Central South University, Changsha, China
• ⁵ Gynecologic Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
• ⁶ Department of Gynecology, Affiliated Tumour Hospital of Nantong University, Nantong, China
• ⁷ Department of Gynecology, Linyi Cancer Hospital, Linyi, China
• ⁸ Obstetrics and Gynaecology, Qilu Hospital of Shandong University, Jinan, China
• ⁹ Department of Oncology, Shanxi Traditional Chinese Medical Hospital,, Taiyuan, China
• ¹⁰ Department of Gynecologic Oncology, The Third Affiliated Hospital of Kunming Medical University/ Yunnan Cancer Hospital,, Kunming, China
• ¹¹ Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
• ¹² Oncology Department, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, China
• ¹³ Department of Gynecological Surgery Three, Affiliated Cancer Hospital of Xinjiang Medical University, Urumchi,, China
• ¹⁴ Oncology Department, Anhui Provincial Cancer Hospital, Hefei, China
• ¹⁵ Oncology Department, Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
• ¹⁶ Oncology Department, Xiangya Hospital of Central South University, Changsha, China
• ¹⁷ First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uyghur Region, China
• ¹⁸ Department of Gynecology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital,, Zhengzhou, China
• ¹⁹ Department of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China
• ²⁰ Gynecology, Jiangsu Province Hospital, Nanjing, China
• ²¹ Radiotherapy Department, Tianjin Medical University General Hospital, Tianjin, China
• ²² Oncology Department, Chongqing University Three Gorges Hospital, Chongqing, China
• ²³ Oncology Department, The second Xiangya Hospital of Central South University, Changsha, China
• ²⁴ Gynecological Oncology, Hubei Cancer Hospital, Wuhan, China
• ²⁵ Oncology Department/Radiotherapy Department, Zhu Jiang Hospital of Southern Medical University, Guangzhou, China
• ²⁶ Department of Tumour Ward, ShangRao People's Hospital, Shangrao, China
• ²⁷ Gynecology Department Ⅱ, Gansu Provincial Maternity and Child Health Hospital, Lanzhou, China
• ²⁸ Radiotherapy Department, Taian City Central Hospital, Taian, China
• ²⁹ Department of Clinical Research and Development, Genor Biopharma Co., Ltd., Beijing, China
• ³⁰ Gynecological radiotherapy Ward 1, Harbin Medical University Cancer Hospital, Harbin, China

Background: This phase II trial investigated the efficacy and safety of Geptanolimab (GB226) in patients with previously treated, PD-L1-Positive recurrent or metastatic cervical cancer. Methods: We enrolled patients who had disease progression after first-line platinum-containing chemotherapy. Geptanolimab was given intravenously at a dose of 3 mg/kg every two weeks until disease progression, unacceptable toxic effects, or withdrawal from the study. The primary endpoint was Independent Review Committee (IRC)-assessed confirmed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results: 169 patients were enrolled from May 2019 to Jan 2022. In 100 efficacy-evaluable patients, the ORR was 18%, the disease control rate was 41%. The median PFS was 1.91 months. The median overall survival was 16.69 months. Furthermore, for 123 safety-evaluable patients, 97(78.9%) patients experienced a treatment-related adverse event. The most frequent treatment-related adverse events were hypothyroidism (30[24.4%]), anaemia (26 [21.1%]) and hyperthyroidism (17 [13.8%]). Conclusions: Geptanolimab as a second-line or later therapy has Promising, durable clinical activity and favourable tolerability for patients with, PD-L1-Positive, ECOG＝1, Squamous cell carcinoma, one prior line of therapy, no prior bevacizumab therapy or CPS ≥20 recurrent or recurrent or metastatic cervical cancer.