Gelonghui, May 24 | Youzhiyou Bio-B (02496.HK) announced that the mid-term analysis data of the Phase I clinical study (“this study”) of the company's self-developed epithelial cell adhesion molecule (“epCAM”) and differentiation cluster 3 (“CD3") dual-targeted bispecific antibody (“BsAb”) drug M701 in China to treat malignant ascites caused by advanced epithelial solid tumors (“this study”) was presented in the 2024 American Society of Clinical Oncology (“ASCO”) abstract meeting in the form of a poster discussion ID: 12060, Poster Number: 189), will also be published on the company's website (corresponding.

This study is a randomized controlled, multicenter, open phase II clinical trial (R&D code: M70102) for malignant ascites caused by advanced epithelial tumors. The study included participants in the test group and control group according to a 1:1 ratio. Subjects in the test group received intraperitoneal drainage and intraperitoneal injection of M701. The dosage and frequency of use of the drug was 50 μg M701 on day 1, and 400 μg, respectively, on days 4, 11, and 18. M701 is then injected intraperitoneally every 2 weeks, and ascites are no longer drained. The control subjects underwent at least 2 laparocentesis drains as needed between day 1 and day 18, followed by no ascites drainage. Both groups of subjects simultaneously received systemic treatment as specified by the researcher. The primary endpoint of the study was puncture-free survival (“PUFs”), defined as the time between the end of the 18th day of treatment and the next puncture or death. Secondary endpoints of the study include overall survival time (“OS”) and probability of adverse events.

As of December 15, 2023, 84 patients with advanced epithelial solid tumors with malignant ascites were enrolled in this study. The median age of both the test group and control group was 54 years old, 33% and 34% of men, 89% and 88% of patients with a physical fitness score (“ECOG”) of 0-1, respectively, 49% of gastric cancer patients, 58% and 56% of previous abdominal cavity medications, and 63% and 54% of previous abdominal puncture treatments. The baseline conditions of the two groups of patients were well balanced.

Curative results:The survival time of the test group without puncture was significantly longer than that of the control group (median value of 54 days versus 24 days, HR = 0.39, p=0.001), and subgroup analysis revealed that subjects with different cancer types such as gastric cancer, ovarian cancer, and colorectal cancer all benefited. Survival analysis showed that subjects treated with M701 showed a trend of prolonged survival (median value of 113 days versus 76 days, HR = 0.45, p = 0.0575). The 6-month survival rates of the test group and control group were 35.2% and 15.8%, respectively. A subgroup analysis of survival time showed a significant increase in the survival time of patients with gastric cancer in the test group (median value of 128 days versus 64 days, HR = 0.45, p = 0.0438).

Safety results:In the test group and control group, the incidence of grade 3 and above treatment emergency adverse events (“TEAE”) was 52% and 57.5%, respectively, and the incidence of serious adverse events (“SAE”) was 38% and 50%, respectively. Among the subjects treated with M701, only 2 patients reported adverse effects of cytokine release syndrome (“CRS”), both grade 1-2.

Conclusions:Patients with solid epithelial tumors with malignant ascites were well tolerated by intraperitoneal perfusion of M701 while undergoing systemic systemic treatment, and did not show a higher risk than patients who only underwent abdominal puncture and drainage. At the same time, patients treated with M701 showed increased survival time without puncture and overall survival time. These results are promising and strongly support the entry of M701 into key research as a novel drug to treat malignant ascites.