An anti-EpCAM x anti-CD3 bispecific antibody, M701, for the treatment of malignant ascites due to epithelial cancer: Interim results of a prospective randomized controlled phase II trial.

12060 Background: Malignant ascites (MA) is a significant complication in patients with late-stage epithelial cancer, associated with poor prognosis, reduced quality of life, and severe symptoms. It is usually caused by tumor cells seeding into the peritoneum, which obstructs lymphatic drainage and increases capillary permeability. Currently, there is no approved drug therapy specifically for the treatment of MA worldwide. Methods: Patients with MA due to epithelial cancer, who had received at least two prior systemic chemotherapy regimens, were enrolled and randomly assigned to the experimental arm (Arm E) and control arm (Arm C). Arm E received paracentesis and intraperitoneal (IP) infusions of 50, 400, 400, and 400μg of M701 on days 1, 4, 11, and 18. Additional M701 infusions could be given every 2 weeks without requiring punctures. Arm C received paracentesis alone as needed from day 1 to day 18. Both arms received systemic tumor treatment as determined by investigators. The primary endpoint was puncture-free survival (PuFS), defined as the time from random assignment to the next puncture or death, whichever occurred first. Secondary endpoints included overall survival (OS) and incidence of adverse events (AEs). Results: As of December 15, 2023, a total of 84 pts were enrolled, with 43 in Arm E and 41 in Arm C. The characteristics of Pts are outlined in the table. PuFS was significantly longer in Arm E compared to Arm C (median 54 vs 24 days, hazard ratios (HR) = 0.39, 95% CI 0.21-0.72, p=0.001). Subgroup analysis of PuFS indicated that patients with different types of cancer (gastric, colorectal and ovarian) all benefited from M701 infusion. OS analysis demonstrated a trend towards prolonged survival in Arm E compared to Arm C (median 113 vs 76 days, HR=0.56, 95% CI 0.31-1.03, p=0.0575). The 6-month survival rates were 35.2% and 15.8%, respectively. Subgroup analysis showed that patients with gastric cancer had significantly longer OS than the controls (median 128 vs 64 days, HR= 0.45, 95%CI 0.20-1.00, p=0.0438). Grade 3 or higher treatment-emergent AEs occurred in 52% of patients in Arm E and 57.5% of patients in Arm C. Serious AEs occurred in 38% and 50% of patients in the two arms, respectively. Only 2 cases of cytokine release syndrome (both grade 2) were reported in patients treated with M701. Conclusions: IP infusions of M701, based on systemic tumor therapy, were well tolerated and did not pose a higher risk compared to the control arm. Epithelial cancer patients with MA who received M701 treatment had longer PuFS and OS. These results are promising and support the pivotal trial of M701 as a novel treatment for MA. [Table: see text]