Abstract CT168: EMB-01, an EGFR/cMET bispecific antibody, in metastatic colorectal cancer: Results from an international phase Ib/II study
Authors: Lin Shen, Christine M. Parseghian, Yanqiao Zhang, Zhiyu Chen, Yanru Qin, Weisheng Zhang, Yanhong Deng, Hongming Pan, Shanzhi Gu, Changzheng Li, Rong Wang, Fang Ren, Qiaoyang Lu, Xiaodong Sun, Yonghong Zhu
Journal: Cancer Research (2025)

Abstract Background: Gastrointestinal (GI) cancers often overexpress epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (cMET). EMB-01, a bispecific tetravalent fully humanized wild-type IgG1 antibody targeting EGFR and cMET, has demonstrated antitumor activity in preclinical and clinical studies with a recommended phase 2 dose (RP2D) of 1600 mg once weekly1,2. This Phase Ib/II study (NCT05176665) evaluates EMB-01 monotherapy in GI cancers, including gastric, hepatocellular, biliary tract and colorectal cancer. Here, we report the preliminary safety and efficacy results in metastatic colorectal cancer (mCRC). Methods: This multicenter, single-arm, open-label study, conducted in China and the US, enrolled patients (pts) with heavily pretreated metastatic GI cancers. EMB-01 was intravenously administered at the RP2D. Response and safety were assessed by the investigator per RECIST v1.1 and CTCAE v5.0, respectively. Results: As of Dec 4, 2024, 48 mCRC pts with different EGFR/cMET expression or amplification status were enrolled. The median age was 60 years (range 41-77), Asian/White was 41/7, ECOG performance status 0/1 was 21/27, 68.8% were male and 91.7% were left-sided mCRC. The median lines of prior systemic therapies were 3 (range 1-11), with 66.7% having received prior anti-EGFR therapy, 79.2% anti-VEGF therapy, and 27.1% fruquintinib, regorafenib, or trifluridine/tipiracil (TAS-102). Among 44 pts evaluable for response, 29 were left-sided, RAS/RAF wild-type mCRC, with median prior lines of 3 (1-7), but no exposure to fruquintinib/regorafenib/TAS-102. Of the 29 pts, 7 (24.1%) achieved partial response (PR), and the disease control rate (DCR) was 86.2%. The median duration of response for 6 confirmed responders was 7.4 months, with 2 PRs still on treatment at data cutoff. Of the 18/29 pts that had progressed on prior anti-EGFR, ORR was 22.2% and DCR was 83.3%. The efficacy was similar between pts with and without liver metastasis. The remaining 15 pts, who were right-sided, RAS/RAF mutant mCRC, or prior heavily treated including fruquintinib/regorafenib/TAS-102 with median prior lines of 4 (2-11), had a DCR of 46.7%, with no PR. Treatment-related adverse events (TRAEs) were reported in 97.9% pts: the most common (≥30%) were rash (60.4%), myalgia (52.1%), paronychia (39.6%) and hypoalbuminemia (35.4%). Serious TRAEs were reported in only 3 (6.3%) pts. No treatment-related deaths. Only 2 (4.2%) pts experienced Grade 1-2 infusion-related reaction. Conclusions: EMB-01 demonstrated promising efficacy in heavily pretreated mCRC, including those with prior progression on anti-EGFR, with an acceptable safety profile at 1600 mg, warranting further investigation in larger cohorts. References: 1. Ren et al. Cancer Res 2020;80(16 Suppl): Abstract 528. 2. Zhou et al. Annals of Oncology (2022) 33 (suppl_2): S27-S70. Abstract 22P. Citation Format: Lin Shen, Christine M. Parseghian, Yanqiao Zhang, Zhiyu Chen, Yanru Qin, Weisheng Zhang, Yanhong Deng, Hongming Pan, Shanzhi Gu, Changzheng Li, Rong Wang, Fang Ren, Qiaoyang Lu, Xiaodong Sun, Yonghong Zhu. EMB-01, an EGFR/cMET bispecific antibody, in metastatic colorectal cancer: Results from an international phase Ib/II study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT168.