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
Presenter: Wei Su Session: Phase 0 and First-in-Human Phase I Clinical Trials Time: 4/20/2026 2:00:00 PM → 4/20/2026 5:00:00 PM
Authors
Shun Lu 1 , Huiping Li 2 , Yinghua Ji 3 , Longhua Sun 4 , Zhangzhou Huang 5 , Huangming Hong 6 , Jianhua Shi 7 , Fangling Ning 8 , Yongmei Yin 9 , Jian Fang 2 , Aobing Bai 10 , Dexuan Zhang 10 , Zhihao Jiang 10 , Qing Yang 10 1 Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China, 2 Peking University Cancer Hospital and Institute, Beijing, China, 3 The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China, 4 The First Affiliated Hospital of Nanchang University, Nanchang, China, 5 Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China, 6 Sichuan Cancer Hospital and Institute, Chengdu, China, 7 Linyi Cancer Hospital, Linyi, China, 8 Binzhou Medical University Hospital, Binzhou, China, 9 The First Affiliated Hospital of Nanjing Medical University, Nanjing, China, 10 Shanghai Junshi Biosciences, Shanghai, China
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.
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.
Cited in
Control: 10132 · Presentation Id: 12053 · Meeting 21436