Phase 3, multicenter, randomized, controlled open-label study: Efficacy and safety of M701 (EpCAM×CD3 bispecific antibody) intraperitoneal infusion in advanced epithelial solid tumor with malignant ascites vs paracentesis.

Abstract

104 Background: Malignant ascites (MA) is a severe complication of advanced epithelial cancers, imposing a heavy symptom burden, compromising systemic therapy efficacy, and correlating with poor survival and impaired quality of life. While only one pharmacologic therapy is approved; guideline-recommended paracentesis provides merely transient symptomatic relief. Consequently, a significant unmet medical need persists for effective therapies that durably control MA. Methods: Patients with malignant ascites (MA) secondary to advanced gastric, colorectal, or ovarian cancer after failure of standard anticancer therapy were enrolled. Patients were randomized to Arm T, receiving therapeutic paracentesis plus intraperitoneal M701, or Arm C, receiving paracentesis alone. All patients continued background systemic treatment. The primary endpoint was puncture-free survival (PuFS), defined as the time from Day 18 to the subsequent paracentesis or death. Secondary endpoints included overall survival (OS), time to next paracentesis (TTNP), patient-reported outcomes (PROs) evaluated using the EORTC QLQ-C30 questionnaire and a Likert scale, and safety profiles between the two arms. Results: As of January 15, 2026, 312 pts were enrolled (Arm T, n = 206; Arm C, n = 106). Median PuFS was significantly longer in Arm T than in Arm C (87.59 vs 49.96 days; HR = 0.57, 95% CI: 0.42–0.78; p = 0.0003). TTNP was also markedly improved with M701 (186.7 vs 55.1 days; HR = 0.42, 95% CI: 0.29–0.60, p < 0.0001). Overall survival was comparable between arms (p = 0.8407, HR = 0.97, 95% CI: 0.74–1.28). Patient-reported outcomes showed a longer median time to global health status deterioration in Arm T (72.0 vs 39.0 days; HR = 0.73, p = 0.049). A statistically significant between-group difference was observed in the change from baseline in total Likert score at Day 116 (Visit 12) (mean difference −2.45; p = 0.0130), indicating sustained symptom relief with M701. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 70.39% of patients in Arm T and 51.89% in Arm C. Serious adverse events (SAEs) occurred in 48.54% and 33.02% of patients in the two arms, respectively. Only one grade 1 cytokine release syndrome (CRS) event was reported in Arm T, and the incidence of CRS-like symptoms (e.g., pyrexia and dyspnea) was very low. Conclusions: Intraperitoneal M701 was well tolerated when combined with systemic therapy. In patients with epithelial cancer-associated MA, M701 significantly prolonged puncture-free survival with comparable overall survival. These encouraging findings further support the clinical development of M701 and its potential therapeutic role in the management of malignant ascites. Clinical trial information: NCT06432296 .