PO.CT01.01 · 临床试验

EGFR/HER3靶向双特异性抗体-药物偶联物（ADC）JS212在晚期实体瘤患者中的首次人体I/II期研究初步结果

Preliminary results from a first-in-human phase I/II study of JS212, an EGFR/HER3-targeted bispecific antibody-drug conjugate (ADC), in patients with advanced solid tumors

编号 CT128 展板 20 时间 4/20 02:00–05:00 区域 Section 51 主讲 Wei Su

分会场 Phase 0 and First-in-Human Phase I Clinical Trials

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作者与单位 Authors & Affiliations

Shun Lu¹, Huiping Li², Yinghua Ji³, Longhua Sun⁴, Zhangzhou Huang⁵, Huangming Hong⁶, Jianhua Shi⁷, Fangling Ning⁸, Yongmei Yin⁹, Jian Fang², Aobing Bai¹⁰, Dexuan Zhang¹⁰, Zhihao Jiang¹⁰, Qing Yang¹⁰

¹Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China,²Peking University Cancer Hospital and Institute, Beijing, China,³The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China,⁴The First Affiliated Hospital of Nanchang University, Nanchang, China,⁵Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China,⁶Sichuan Cancer Hospital and Institute, Chengdu, China,⁷Linyi Cancer Hospital, Linyi, China,⁸Binzhou Medical University Hospital, Binzhou, China,⁹The First Affiliated Hospital of Nanjing Medical University, Nanjing, China,¹⁰Shanghai Junshi Biosciences, Shanghai, China

摘要 Abstract

中文摘要

背景：JS212是一种exatecan偶联的EGFR和HER3双特异性ADC。这项首次人体I/II期研究（NCT06888830）旨在评估JS212在晚期实体瘤患者中的安全性、耐受性、药代动力学和初步疗效。方法：本研究包括剂量递增和扩展（第1部分）以及临床扩展（第2部分）。剂量递增采用加速滴定法起始（0.6 mg/kg每3周[Q3W]），随后采用贝叶斯最优区间设计（1.2、1.8、2.4、3.0、3.6、4.2和4.8 mg/kg Q3W）。在2个或更多剂量水平进行剂量扩展以确定2期推荐剂量（RP2D）。第1部分的主要终点为安全性、最大耐受剂量（MTD）和RP2D。第2部分将进一步评估JS212在特定肿瘤类型中的疗效和安全性，主要终点为客观缓解率（ORR）。结果：截至2026年2月6日，共有57例患者（31例非小细胞肺癌[NSCLC]、9例乳腺癌[BC]和17例食管鳞状细胞癌[ESCC]）入组第1部分，其中40例接受剂量递增，17例接受剂量扩展。患者既往接受过1至5线系统性抗肿瘤治疗。所有ESCC患者既往均接受过免疫检查点抑制剂治疗，所有EGFR突变NSCLC患者均接受过既往第三代EGFR酪氨酸激酶抑制剂治疗。评估了高达4.8 mg/kg Q3W的JS212剂量。中位随访3.1个月，观察到2例剂量限制性毒性（1例在4.2 mg/kg Q3W，1例在4.8 mg/kg Q3W），尚未达到MTD。≥3级治疗相关不良事件（TRAE）的发生率为22.8%；最常见的≥3级TRAE为中性粒细胞减少（15.8%）和白细胞减少（10.5%）。在48例可评估疗效的患者中，ORR为29.2%（14/48）。在剂量≥1.8 mg/kg Q3W的患者中（n=42），ESCC的ORR为45.5%（5/11），HR+/HER2− BC的ORR为37.5%（3/8）（均在≤3.6 mg/kg Q3W剂量水平下观察到）；EGFR突变NSCLC的ORR为30.0%（3/10），疾病控制率为90.0%（9/10）。结论：JS212在一系列剂量水平和多种实体瘤类型中显示出令人鼓舞的抗肿瘤活性，且安全性可耐受。

查看英文原文 English abstract

Background: JS212 is an exatecan-conjugated EGFR and HER3 bispecific ADC. This first-in-human phase I/II study (NCT06888830) was designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of JS212 in patients with advanced solid tumors. Methods: This study comprised dose escalation and expansion (Part 1) and clinical expansion (Part 2). Dose escalation was initiated using an accelerated titration (0.6 mg/kg every 3 weeks [Q3W]), followed by a Bayesian Optimal Interval design (1.2, 1.8, 2.4, 3.0, 3.6, 4.2, and 4.8 mg/kg Q3W). Dose expansion was conducted at 2 or more dose levels to determine the recommended phase 2 dose (RP2D). The primary endpoints of Part 1 were safety, maximum tolerated dose (MTD), and RP2D. Part 2 will further evaluate the efficacy and safety of JS212 across selected tumor types, with the primary endpoint of objective response rate (ORR). Results: As of February 6, 2026, a total of 57 patients (31 with non-small-cell lung cancer [NSCLC], 9 with breast cancer [BC], and 17 with esophageal squamous carcinoma [ESCC]) were enrolled in Part 1, including 40 in dose escalation and 17 in dose expansion. Patients had received 1 to 5 prior lines of systemic anti-tumor therapy. All patients with ESCC had been previously treated with immune checkpoint inhibitors, and all patients with EGFR-mutant NSCLC had received prior third-generation EGFR tyrosine kinase inhibitors. JS212 doses up to 4.8 mg/kg Q3W were evaluated. With a median follow-up of 3.1 months, two dose limiting toxicities were observed (one at 4.2 mg/kg Q3W and one at 4.8 mg/kg Q3W) and the MTD has not yet been reached. The incidence of grade ≥3 treatment-related adverse events (TRAE) was 22.8%; the most common grade ≥3 TRAEs were neutropenia (15.8%) and leukopenia (10.5%). Among 48 efficacy-evaluable patients, the ORR was 29.2% (14/48). Among the patients at doses ≥1.8 mg/kg Q3W (n=42), the ORR was 45.5% (5/11) for ESCC and 37.5% (3/8) for HR+/HER2− BC (all observed at ≤3.6 mg/kg Q3W dose levels); for EGFR-mutant NSCLC, the ORR was 30.0% (3/10), and the disease control rate was 90.0% (9/10). Conclusions: JS212 showed encouraging antitumor activity across a range of dose levels and multiple solid tumor types with a tolerable safety profile.

利益披露 Disclosure

S. Lu, None.. H. Li, None.. Y. Ji, None.. L. Sun, None.. Z. Huang, None.. H. Hong, None.. J. Shi, None.. F. Ning, None.. Y. Yin, None.. J. Fang, None. A. Bai, Shanghai Junshi Biosciences Employment. D. Zhang, Shanghai Junshi Biosciences Employment. Z. Jiang, Shanghai Junshi Biosciences Employment. Q. Yang, Shanghai Junshi Biosciences Employment, Stock Option.

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