EMB-01, an Anti-EGFR/c-MET Bispecific Antibody, in Patients with Heavily Pretreated Metastatic Colorectal Cancer from a Phase Ib/II, Open-Label, Multicenter Study

作者：Ting Xu, Christine M. Parseghian, Yanqiao Zhang, Zhiyu Chen, Yanru Qin, Weisheng Zhang, Yanhong Deng, Hongming Pan, Shanzhi Gu, Changzheng Li, Fang Ren, Ying Wu, Qiaoyang Lu, Mingfei Zhang, Rong Wang, Yonghong Zhu, Lin Shen, Jian Li · 发表于：Clinical Cancer Research · 年份：2026 · DOI：10.1158/1078-0432.ccr-26-2128 · 研究领域：Colorectal Cancer Treatments and Studies、HER2/EGFR in Cancer Research、Cancer Cells and Metastasis

Purpose EMB-01 is a novel EGFR × c-MET bispecific antibody. The phase Ib/II study (NCT05176665) presents the safety and antitumor activity of EMB-01 in patients predominantly with heavily pretreated metastatic colorectal cancer (mCRC). Patients and methods EMB-01 was administered at 1600 mg intravenously weekly. Primary endpoints were safety and tolerability in phase Ib, and antitumor activity in phase II. Secondary endpoints included cross-phase validation of antitumor activity and safety. Exploratory endpoints included biomarker analysis. Results Fifty-two patients were enrolled (phase Ib, n=27; phase II, n=25). All patients (100%) experienced at least one treatment-emergent adverse event (TEAE), and 98.1% experienced treatment-related adverse events (TRAEs). Grade ≥ 3 TRAEs occurred in 63.5% of patients, with rash (25.0%) and dermatitis acneiform (17.3%) most frequently. Among the 48 mCRC patients, the confirmed objective response rate (cORR) was 12.5% (95% confidence interval [CI], 4.7 to 25.2%), with a median duration of response (DOR) of 32.0 weeks (95% CI, 16.0 to not estimable). All responses were observed in a favorable mCRC subgroup with evaluable response (left-sided, RAS/RAF wild-type, naïve to fruquintinib/regorafenib/trifluridine-tipiracil [TAS-102]; n=29). In this subgroup, the unconfirmed ORR (uORR) and the cORR were 24.1% (95% CI, 10.3 to 43.5%) and 20.7% (95% CI, 8.0 to 39.7%), respectively. Median progression-free survival (mPFS) was 19.0 weeks (95% CI, 12....