恩隆斯托巴特（SG001），一种新型PD - 1抑制剂，用于PD - L1阳性复发/转移性宫颈癌患者的II期研究。
Phase II study of enlonstobart (SG001), a novel PD-1 inhibitor in patients with PD-L1 positive recurrent/metastatic cervical cancer.
作者信息
Li Guiling, Li Xiaofan, Yin Rutie, Feng Mei, Zuo Jing, Wei Shuqing, Kang Shan, Sun Hongmei, Li Xiumin, Wang Yili, Zhang Yunyan, Sun Li, Lin Daren, Ruan Xiaohong, Zhu Zhitu, Jiang Kui, Liu Hu, Wang Wei, Hao Deshun, Chen Ying, Xiang Silong, Niu Miao, Wu Lingying
机构信息
Department of Gynecologic Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
出版信息
Gynecol Oncol. 2024 Dec;191:165-171. doi: 10.1016/j.ygyno.2024.10.001. Epub 2024 Oct 23.
BACKGROUND
Platinum-based chemotherapy with or without bevacizumab is the first-line treatment for patients with recurrent or metastatic cervical cancer (r/mCC), and the treatment options are limited for r/mCC after first-line treatment. Enlonstobart (SG001) is a fully humanized and high-affinity anti-PD-1 immunoglobulin G4 monoclonal antibody. Previous phase Ib study demonstrated that SG001 had a promising efficacy in patients with PD-L1 positive r/mCC.
METHODS
In this multicenter, single-arm, open-label, phase II study, eligible patients were ≥ 18 years with PD-L1-positive cervical cancer who had progression on or intolerance to the first-line platinum-based chemotherapy. Patients received SG001 240 mg every two weeks for 24 months or until disease progression, intolerable toxicities, or other study discontinuation criteria were met. The primary endpoint was confirmed objective response rate (ORR) assessed by RECIST version 1.1 by independent review committee.
RESULTS
107 patients were enrolled with median age of 53 years (range 26-72). 64.5 % of patients had a ECOG of 1. After a median follow-up of 14.0 months (range 0.4-21.9), confirmed ORR was 29.0 %, with two complete responses and twenty-nine partial responses. The disease control rate was 54.2 %. Median duration of response was 16.6 months (95 % CI 10.8-NA), median progression free survival was 3.1 months (95 % CI 2.2-6.9). Median overall survival was not reached. 104 patients (97.2 %) experienced at least one treatment emergent adverse events TEAEs, of which 38 patients (35.5 %) had grade 3 or higher TEAEs. The most common treatment-related adverse events were leukopenia (19.6 %), increased aspartate aminotransferase (18.7 %), anemia (17.8 %), increased alanine aminotransferase (15.9 %), hypothyroidism (15.0 %), neutropenia (15.0 %), and hyperthyroidism (11.2 %).
CONCLUSION
SG001 monotherapy demonstrated durable anti-tumor activity with acceptable safety in patients with PD-L1 positive r/mCC with progression on or intolerance to the first-line platinum-based chemotherapy.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT04886700).
背景
含或不含贝伐单抗的铂类化疗是复发性或转移性宫颈癌（r/mCC）患者的一线治疗方案，一线治疗后r/mCC的治疗选择有限。恩隆斯托巴特（SG001）是一种完全人源化且高亲和力的抗PD-1免疫球蛋白G4单克隆抗体。先前的Ib期研究表明，SG001在PD-L1阳性的r/mCC患者中具有良好的疗效。
方法
在这项多中心、单臂、开放标签的II期研究中，符合条件的患者年龄≥18岁，患有PD-L1阳性宫颈癌，且对一线铂类化疗有进展或不耐受。患者每两周接受240mg的SG001治疗，持续24个月，或直至疾病进展、出现无法耐受的毒性或满足其他研究终止标准。主要终点是由独立审查委员会根据RECIST 1.1版评估的确认客观缓解率（ORR）。
结果
共纳入107例患者，中位年龄53岁（范围26 - 72岁）。64.5%的患者ECOG评分为1。中位随访14.0个月（范围0.4 - 21.9个月）后，确认的ORR为29.0%，包括2例完全缓解和29例部分缓解。疾病控制率为54.2%。中位缓解持续时间为16.6个月（95%CI 10.8 - NA），中位无进展生存期为3.1个月（95%CI 2.2 - 6.9）。中位总生存期未达到。104例患者（97.2%）经历了至少一次治疗期间出现的不良事件（TEAE），其中38例患者（35.5%）发生3级或更高等级的TEAE。最常见的治疗相关不良事件为白细胞减少（19.6%）、天冬氨酸转氨酶升高（18.7%）、贫血（17.8%）、丙氨酸转氨酶升高（15.9%）、甲状腺功能减退（15.0%）、中性粒细胞减少（15.0%）和甲状腺功能亢进（11.2%）。
结论
对于一线铂类化疗有进展或不耐受的PD-L1阳性r/mCC患者，SG001单药治疗显示出持久的抗肿瘤活性且安全性可接受。
试验注册
ClinicalTrials.gov（NCT04886700）
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