Wuhan YZY Biopharma's M701 Shows Superior Efficacy Over Cisplatin in Phase II Trial for Malignant Pleural Effusion
核心洞察
Wuhan YZY Biopharma (搜索)'s M701, a bispecific antibody targeting EpCAM (搜索) and CD3 (搜索), demonstrated longer puncture-free survival compared to cisplatin in treating malignant pleural effusion (搜索) from advanced NSCLC (搜索).
The experimental group showed median puncture-free survival of 130 days versus 85 days for cisplatin, with particularly pronounced benefits in patients without driver gene mutations.
M701 exhibited superior safety profile with only 3.7% treatment-related adverse events compared to 10% with cisplatin, supporting advancement to Phase III trials planned for 2026.
Wuhan YZY Biopharma (搜索) Co., Ltd. has announced promising interim results from its Phase II clinical trial of M701, a bispecific antibody drug targeting epithelial cell adhesion molecule (搜索) (EpCAM (搜索)) and cluster of differentiation 3 (CD3 (搜索)), for treating malignant pleural effusion (搜索) (MPE) caused by advanced non-small cell lung cancer (搜索) (NSCLC (搜索)). The data, presented at the 2025 European Society for Medical Oncology (ESMO) Congress, showed superior efficacy compared to the standard cisplatin treatment.
Trial Design and Patient Population
The randomized, controlled, multicenter, open-label Phase II clinical trial (development code: M70103) enrolled 54 eligible patients with advanced NSCLC (搜索) who had progressed after at least one line of systemic therapy and exhibited symptomatic malignant pleural effusion (搜索). Participants were randomly assigned in a 1:1 ratio to receive either intrapleural infusion of M701 (26 patients) or cisplatin (28 patients) after thoracentesis and drainage.
The median age was 66.5 years in the experimental group and 61.5 years in the control group. Female patients comprised 57.7% and 50.0% of the experimental and control groups, respectively. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 accounted for 92.3% and 96.4%, respectively. The proportion of patients positive for driver gene mutations was 76.9% and 78.6%, respectively.
Efficacy Outcomes
The primary endpoint of puncture-free survival time (PuFS) showed favorable results for M701, with the experimental group achieving a median of 130 days compared to 85 days in the cisplatin control group (hazard ratio = 0.80, p = 0.542). The benefits were particularly pronounced in specific patient subgroups.
For patients negative for driver gene mutations, the results were striking, with median puncture-free survival not reached in the M701 group versus 44.5 days in the cisplatin group (HR < 0.01, p < 0.001). Similarly, patients with a history of intrapleural chemotherapy showed substantial improvement with M701, achieving median puncture-free survival of 253 days compared to 72 days with cisplatin (HR = 0.31, p = 0.076).
The objective response rate (ORR) of malignant pleural effusion (搜索) in these beneficial populations reached 72.7% for M701 compared to 41.7% for cisplatin. Additionally, after 98 days of randomization, only patients in the experimental group showed sustained improvement in dyspnea symptoms.
Mechanistic Insights
Flow cytometry analysis provided mechanistic evidence for M701's efficacy, revealing a significant reduction in EpCAM (搜索)+CD45- tumor cells in the pleural effusion following M701 infusion. This phenomenon was not observed in the control group receiving cisplatin, suggesting M701's targeted mechanism of action effectively eliminates tumor cells in the pleural space.
Safety Profile
M701 demonstrated a superior safety profile compared to cisplatin. The incidence of treatment-related adverse events was notably lower with M701 at 3.7% compared to 10% in the cisplatin group. Only one serious adverse event, a grade 2 fever, was related to M701 treatment, highlighting the drug's favorable tolerability profile.
Clinical Implications and Future Development
The interim results suggest M701's potential as an effective treatment for malignant pleural effusion (搜索), particularly for NSCLC (搜索) patients without driven gene mutations or those previously treated with intrapleural chemotherapy. The bispecific antibody's ability to provide sustained control over pleural effusion reaccumulation while maintaining excellent tolerability represents a significant advancement in managing this challenging complication of advanced lung cancer.
Based on these encouraging results, Wuhan YZY Biopharma (搜索) plans to initiate a pivotal Phase III trial in 2026 to validate M701's efficacy and safety in a larger Chinese population. The ongoing Phase II trial continues to demonstrate considerable potential in preventing pleural effusion reaccumulation, supporting the drug's progression through clinical development.