2. Academic Validation
  3. Development and clinical trial of M701, an Anti-EpCAM × Anti-CD3 bispecific antibody: a targeted intraperitoneal therapy for malignant ascites stemming from advanced solid tumors

Development and clinical trial of M701, an Anti-EpCAM × Anti-CD3 bispecific antibody: a targeted intraperitoneal therapy for malignant ascites stemming from advanced solid tumors

  • Exp Hematol Oncol. 2025 Nov 22;14(1):136. doi: 10.1186/s40164-025-00727-3.
Rongrui Liu 1,  Rongbo Lin 2,  Ning Li 3,  Guiling Li 4,  Tao Zhang 5,  Jun Zhao 6,  Jiayi Li 7,  Meili Sun 8,  Ke Wang 9,  Hanxiang An 10,  Weijie Zhang 11,  Huiting Xu 12,  Shan Zeng 13,  Mingjun Zhang 14,  Wei Duan 15,  Yuxian Bai 16,  Jingdong Zhang 17,  He Tian 18,  Fei Yin 19,  Yu Kang 20,  Qi Xu 21,  Nong Xu 22,  Yanhong Deng 23,  Qing Chen 24,  Yongqiang Li 25,  Hongying Yang 26,  Fang Su 27,  Zhenghong Xiao 28,  Xiaojun Xiang 29,  Pengfei Zhou 30,  Shaoyi Huang 30,  Jing Zhang 30,  Jianming Xu 31
Affiliations

Affiliations

  • 1 Department of Oncology, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100039, China.
  • 2 Department of Abdominal Oncology, Fujian Cancer Hospital, No. 420 Fuma Road, Fuzhou, 350000, China.
  • 3 Department of Gastrointestinal Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No. 127 Dongming Road, Zhengzhou, 450000, Henan, China.
  • 4 Department of Gynecologic Oncology, Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430000, Hubei, China.
  • 5 Department of Abdominal Oncology, Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430000, China.
  • 6 Department of Oncology, Changzhi People's Hospital, The Affiliated Hospital of Changzhi Medical College, No. 502 Changxing Middle Road, Changzhi, 046000, China.
  • 7 Department of Medical Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, No. 55 Zhenhai Road, Xiamen, 361005, China.
  • 8 Department of Oncology, Jinan Central Hospital affiliated to Shandong University, No. 105 Jiefang Road, Jinan, 250013, China.
  • 9 Department of Gynecological Oncology, Tianjin Medical University Cancer Institute and Hospital, West Huan-Hu Road, Tianjin, 300060, China.
  • 10 Department of Gastrointestinal Oncology, The Cancer Center, Shanxi Bethune Hospital, Shanxi Medical University, No. 99 Longcheng Street, Taiyuan, 030032, China.
  • 11 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Dong Road, Zhengzhou, 450052, China.
  • 12 Department of Medical Oncology, Hubei Cancer Hospital, No. 116 Zhuodaoquan South Road, Wuhan, 430079, China.
  • 13 Department of Chemotherapy Oncology, Xiangya Hospital of Central South University, No. 87 Xiangya Road, Changsha, 410008, China.
  • 14 Department of Oncology, The second hospital of Anhui medical university, No. 678 Furong Road, Hefei, 230601, China.
  • 15 Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No. 17 Qihelou, Beijing, 100069, China.
  • 16 Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China.
  • 17 Department of Gastroenterology, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Shenyang, 110042, China.
  • 18 Department of Gastroenterology, Shandong Cancer Hospital, No. 440 Jiyan Road, Jinan, 250117, China.
  • 19 Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, No. 12 Jiankan Road, Shijiazhuang, 050011, China.
  • 20 Department of Gynecological Oncology, Obstetrics and Gynecology Hospital of Fudan University, No. 419 Fangxie Road, Shanghai, 200011, China.
  • 21 Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Zhejiang Cancer Hospital, No. 1 East Banshan Road, Hangzhou, 310022, China.
  • 22 Department of Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China.
  • 23 Department of Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuancun Er Heng Road, Guangzhou, 510655, China.
  • 24 Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, China.
  • 25 The First Department of Chemotherapy, Affiliated Cancer Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021, China.
  • 26 Department of Gynaecology, Yunnan Cancer Hospital, No. 519 Kunzhou Road, Kunming, 650118, China.
  • 27 Department of Oncology, The First Affiliated Hospital of Bengbu Medical University, 287 Changhuai Road, Bengbu, China.
  • 28 Department of Oncology, Nanshi Hospital of Nanyang, No. 130 Zhongzhou West Road, Nanyang, 473001, China.
  • 29 Department of Oncology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwai Main Street, Nanchang, 330006, China.
  • 30 Wuhan YZY Biopharma Co. Ltd., C2-1 Building, Guanggu Biolake, No. 666, Gaoxin Avenue, Wuhan, 430000, China.
  • 31 Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, No. 8 Dongdajie, Beijing, 100071, China. [email protected].
PMID: 41275209 DOI: 10.1186/s40164-025-00727-3
Abstract

Background: Malignant ascites (MA) is one of the major complications in advanced epithelial Cancer patients and is associated with poor prognosis, poor quality of life, and severe symptoms. No efficient medicine is available for treating MA worldwide. Only paracentesis is recommended by the guidelines in most countries, but with limited efficacy and a short control time. Thus, novel treatments are needed to control MA.

Methods: An anti-EpCAM × anti-CD3 bispecific antibody, M701, was constructed as a T-cell engager to eliminate tumor cells in the peritoneal cavity. A phase II study was performed to evaluate the efficacy and safety of the intraperitoneal (IP) infusion of M701 in advanced epithelial tumor patients with moderate-to-large-scale MA. In this study, 84 patients were enrolled, with 43 in the M701 group receiving paracentesis and IP M701 infusion and 41 in the control group receiving paracentesis alone.

Results: The primary endpoint, median puncture-free survival (PuFS), was 75 days in the M701 group and 25 days in the control group, with a significant difference (p = 0.0065). Subgroup analysis indicated that different types of Cancer, including gastric, colorectal, and ovarian cancers, all benefited from the M701 infusion. Patients with higher relative lymphocyte counts (≥ 13%) at baseline received better effects. Compared to patients in the control group, the overall survival (OS) of patients in the M701 group was certain extended (mOS 110 days vs. 76 days, p = 0.1443, HR = 0.68). The 6-month survival rates were 33.3% and 12.1% in the two groups, respectively. No additional serious adverse events (SAEs) were detected in the M701 group. The most frequent treatment-related adverse events were anemia and low white blood cell count, which were manageable. M701 infusions did not cause a greater risk than paracentesis alone in the control arm, while all patients were administered systemic treatment.

Conclusion: When treated with M701, patients with MA had significantly longer puncture intervals and a trend of extended survival time. The results were encouraging for patients with MA. A phase III clinical trial of M701 aimed at further validation is ongoing.

Keywords

Bispecific antibody; CD3; EpCAM; Intraperitoneal therapy; Malignant ascites; Puncture-free survival.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P991526
    99.05%, EpCAM/CD3 Bispecific Antibody
    CD3