PO.CT01.05 · 临床试验

一项评估JS207（一种靶向PD-1和VEGF的双特异性抗体）联合化疗治疗转移性结直肠癌患者的安全性和疗效的II期试验初步结果

Preliminary results from a phase II trial evaluating the safety and efficacy of JS207, a bispecific antibody targeting PD-1 and VEGF, in combination with chemotherapy in patients with metastatic colorectal cancer

编号 CT152 展板 16 时间 4/20 02:00–05:00 区域 Section 52 主讲 Wei Su

分会场 Phase II and Phase III Clinical Trials

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作者与单位 Authors & Affiliations

Yong Gao¹, Zhiwei Li², Jianwei Yang³, Shuqing Jin⁴, Yiyi Yu⁵, Chang Wang⁶, Xiwen Huang⁷, Jingdong Zhang⁸, Yanhong Gu⁹, Shuqin Ni¹⁰, Yanlai Sun¹⁰, Shirong Cai¹¹, Liang Han¹², Xinjun Liang¹³, Haichuan Su¹⁴, Chenxi Wang¹⁵, Zhenyu Xu¹⁵, Jing Xu¹⁵, Chengbo Jia¹⁵, Jianjun Zou¹⁵, Lin Shen¹⁶

¹Shanghai East Hospital, Shanghai, China,²Harbin Medical University Cancer Hospital, Harbin, China,³Fujian Caner Hospital, Fuzhou, China,⁴First Affiliated Hospital of Wenzhou Medical University, Whenzhou, China,⁵Zhongshan Hospital Affiliated to Fudan University, Shanghai, China,⁶The First Hospital of Jilin University, Changchun, China,⁷Meizhou People's Hospital (Huangtang Hospital), Meizhou, China,⁸Liaoning Cancer Research Institute, Shenyang, China,⁹The First Affiliated Hospital of Nanjing Medical University, Nanjing, China,¹⁰Shandong Cancer Hospital & Institute, Jinan, China,¹¹The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China,¹²Xuzhou Central Hospital, Xuzhou, China,¹³Hubei Cancer Hospital, Wuhan, China,¹⁴Tangdu Hospital, the Fourth Military Medical University, Xi'an, China,¹⁵Shanghai Junshi Biosciences, Shanghai, China,¹⁶Peking University Cancer Hospital & Institute, Beijing, China

摘要 Abstract

中文摘要

背景：JS207是一种靶向程序性死亡受体1和血管内皮生长因子A的双特异性IgG4抗体。这项II期研究（NCT06885385）评估了JS207联合XELOX（卡培他滨+奥沙利铂）作为转移性结直肠癌（mCRC）一线治疗的初步安全性和疗效。方法：既往未针对转移性疾病接受过系统抗肿瘤治疗，或在末次新辅助/辅助治疗后至少12个月复发/进展的mCRC患者符合入组条件。在初始安全导入期，入组6至9例患者以评估JS207 10 mg/kg每3周联合XELOX的安全性和耐受性。患者接受治疗直至进展或不可接受的毒性，JS207持续使用最多2年，奥沙利铂限制在6-8个周期，随后患者转为卡培他滨维持治疗。在安全性可接受后，研究将进入扩展期。主要终点为安全性、推荐III期剂量和客观缓解率（ORR）。结果：截至2025年12月18日，32例患者入组并接受了JS207联合XELOX治疗，包括安全导入期9例和剂量扩展期23例。所有患者均为微卫星稳定/错配修复功能完整的CRC。中位年龄为61岁（范围：36-74），56%的患者原发肿瘤位于左半结肠，44%位于右半结肠。基线时，53%的患者有肝转移，50%有肺转移。截至数据截止日期，中位治疗持续时间为3.56（范围：0.49-7.03）个月。中位随访为4.19（范围：0.82-7.03）个月。未报告剂量限制性毒性。治疗中出现的不良事件（TEAEs）发生于96.9%的患者，46.9%的患者发生≥3级TEAEs。最常见的TEAEs（发生率≥20%）包括中性粒细胞减少（46.9%）、贫血（40.6%）、血小板减少（40.6%）、白细胞减少（37.5%）、天门冬氨酸氨基转移酶升高（28.1%）、血乳酸脱氢酶升高（25.0%）、食欲减退（25.0%）、低白蛋白血症（25.0%）、呕吐（25.0%）、蛋白尿（25.0%）和γ-谷氨酰转移酶升高（21.9%）。最常见的≥3级TEAEs为中性粒细胞减少、白细胞减少、腹泻、肠梗阻和不适，各发生于2例患者。在31例接受至少一次基线后肿瘤评估的患者中，21例达到部分缓解，9例达到疾病稳定。ORR为67.7%，疾病控制率为96.8%。在本次分析时，中位无进展生存期和中位缓解持续时间均未达到。结论：JS207联合XELOX作为mCRC患者的一线治疗显示出可接受的安全性特征和有前景的疗效。

查看英文原文 English abstract

Background: JS207 is a bispecific IgG4 antibody targeting programmed death receptor 1 and vascular endothelial growth factor A. This Phase II study (NCT06885385) evaluated the preliminary safety and efficacy of JS207 combined with XELOX (capecitabine + oxaliplatin) as first-line therapy for metastatic colorectal cancer (mCRC). Methods: Patients with mCRC who have not received prior systemic antitumor therapy for metastatic disease, or recurred/progressed at least 12 months after last neoadjuvant/adjuvant therapy were eligible for enrollment. In the initial safety run-in phase, 6 to 9 patients were enrolled to evaluate the safety and tolerability of JS207 10 mg/kg, every 3 weeks with XELOX. Patients received treatment until progression or unacceptable toxicity, with JS207 continued for up to 2 years and oxaliplatin capped at 6-8 cycles, patients then transitioned to capecitabine maintenance therapy. Upon acceptable safety, the study would enter the expansion phase. The primary endpoints were safety, recommended phase III dose, and objective response rate (ORR). Results: As of December 18, 2025, 32 patients were enrolled and received JS207 in combination with XELOX, including 9 in the safety run-in phase and 23 in the dose-expansion phase. All patients were microsatellite stability/mismatch repair proficient CRC. The median age was 61 (range: 36-74) years, with 56% of the patients having primary tumors located in the left‑sided colon and 44% in the right‑sided colon. At baseline, 53% of patients had liver metastases, and 50% had lung metastases. By the cutoff date, the median treatment duration was 3.56 (range: 0.49-7.03) months. The median follow-up was 4.19 (range: 0.82-7.03) months. No dose limiting toxicity was reported. Treatment emergent adverse events (TEAEs) occurred in 96.9% of patients, with grade ≥ 3 TEAEs in 46.9% of patients. The most frequent TEAEs (incidence ≥ 20%) included neutropenia (46.9%), anemia (40.6%), thrombocytopenia (40.6%), leukopenia (37.5%), aspartate aminotransferase increased (28.1%), blood lactate dehydrogenase increased (25.0%), decreased appetite (25.0%), hypoalbuminemia (25.0%), vomiting (25.0%), proteinuria (25.0%), and gamma-glutamyltransferase increased (21.9%). The most common grade ≥3 TEAEs were neutropenia, leukopenia, diarrhea, intestinal obstruction, and malaise, occurring in 2 patients each. Among 31 patients who underwent at least one post-baseline tumor assessment, 21 achieved a partial response and 9 achieved stable disease. The ORR was 67.7% and the disease control rate was 96.8%. At the time of this analysis, the median progression-free survival and median duration of response had not been reached. Conclusions: JS207 in combination with XELOX as first-line treatment for mCRC patients demonstrated an acceptable safety profile and promising efficacy.

利益披露 Disclosure

Y. Gao, None.. Z. Li, None.. J. Yang, None.. S. Jin, None.. Y. Yu, None.. C. Wang, None.. X. Huang, None.. J. Zhang, None.. Y. Gu, None.. S. Ni, None.. Y. Sun, None.. S. Cai, None.. L. Han, None.. X. Liang, None.. H. Su, None. C. Wang, Shanghai Junshi Biosciences Employment. Z. Xu, Shanghai Junshi Biosciences Employment. J. Xu, Shanghai Junshi Biosciences Employment. C. Jia, Shanghai Junshi Biosciences Employment. J. Zou, Shanghai Junshi Biosciences Employment, Stock Option. L. Shen, None.

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