YZYBIO-B (02496): Mid-term data from the Phase II study of M701 for malignant pleural effusion will be presented at the 2025 ESMO conference.

YZYBIO-B (02496) announced that the mid-term data of the ongoing Phase II clinical study of the bi-specific antibody (BsAb) drug M701, targeting epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 3 (CD3) developed independently by the company, for the treatment of malignant pleural effusion caused by advanced non-small cell lung cancer (NSCLC) in China was presented in the form of a poster at the 2025 European Society for Medical Oncology (ESMO) Congress (poster number: 1880P) and will also be published on the company's website (https://www.yzybio.com). This study is a randomized, controlled, multicenter, open-label Phase II clinical trial (development code: M70103) for malignant pleural effusion caused by advanced NSCLC. The study enrolled subjects in the experimental group and control group in a 1:1 ratio. Subjects in the experimental group received intrapleural infusion of M701 drug after pleural effusion drainage, while subjects in the control group received intrapleural infusion of cisplatin after pleural effusion drainage. The primary endpoint of the study is puncture-free survival (PuFS), defined as the time from the end of treatment to the onset of intolerable malignant pleural effusion or death, which is a composite time event endpoint that directly reflects the control time of malignant pleural effusion by local treatment. Secondary endpoints of the study include objective response rate (ORR) of malignant pleural effusion, time to next puncture (TTNP), symptoms and signs related to malignant pleural effusion, pharmacokinetics, and immunogenicity. As of March 7, 2025, a total of 54 eligible patients with symptomatic malignant pleural effusion caused by advanced NSCLC, who had progressed after at least first-line systemic treatment, were included in the study in a 1:1 randomization, with 26 patients in the experimental group and 28 patients in the control group. The median age of patients in the experimental group was 66.5 years, while in the control group it was 61.5 years. The percentage of female patients in the experimental group and control group was 57.7% and 50.0% respectively, and the percentage of patients with a performance status score (ECOG) of 0-1 was 92.3% and 96.4% in the experimental group and control group respectively. The proportion of patients with baseline pleural effusion volume of moderate or above (500mL) was 65.4% and 67.9% in the experimental group and control group, respectively. The proportion of patients who had previously received pleural effusion drainage treatment was 65.4% and 71.4% in the experimental group and control group, and the percentage of patients with positive driver gene mutations were 76.9% and 78.6% in the two groups, respectively. The proportion of patients who had previously received intrapleural chemotherapy was 42.3% in the experimental group and 35.7% in the control group. Apart from the older age of patients in the experimental group, the baseline characteristics of the two groups were relatively balanced. Efficacy results: The puncture-free survival time of the experimental group was longer than that of the control group (median 130 days vs. 85 days, hazard ratio (HR) = 0.80, p = 0.542), and this benefit was more pronounced in patients who were driver gene negative (median not reached vs. 44.5 days, HR < 0.01, p < 0.001) or had a history of intrapleural chemotherapy (median 253 days vs. 72 days, HR = 0.31, p = 0.076). In these populations, the objective response rate of malignant pleural effusion (MPE ORR) in the experimental group and control group was 72.7% and 41.7%, respectively. After 98 days of randomization, only patients in the experimental group showed continued improvement in respiratory symptoms. Flow cytometry analysis showed a significant reduction in EpCAM+CD45-tumor cells in pleural effusion after M701 infusion, while this phenomenon was not observed in the control group receiving cisplatin. Safety results: The incidence of M701 treatment-related adverse events was 3.7%, while in the cisplatin group it was 10%. Only one serious adverse event (grade 2 fever) was related to M701. Conclusion: Compared to cisplatin, intrapleural infusion of M701 has shown significant efficacy in treating malignant pleural effusion and good tolerability, providing support for its further clinical development, especially for patients with non-driver gene mutations of NSCLC or those who have previously received intrapleural chemotherapy. This Phase II trial is still ongoing and has shown considerable potential in preventing the reaccumulation of pleural effusion, especially in patients with driver gene negative NSCLC or those who have received intrapleural chemotherapy in the past. Based on the current excellent results, a key Phase III trial is planned to be initiated in 2026 to validate its effectiveness and safety in a large population of Chinese patients.