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

According to the news from Zhitong Finance APP, YZYBIO-B (02496) announced that the mid-term data of its self-developed dual-target bispecific antibody (Bs Ab) drug M701, which targets epithelial cell adhesion molecule (Ep CAM) and cluster of differentiation 3 (CD3), in a Phase II clinical study for the treatment of malignant pleural effusion caused by advanced non-small cell lung cancer (NSCLC) in China has been presented in the form of a conference poster at the 2025 European Society for Medical Oncology (ESMO) (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) targeting malignant pleural effusion caused by advanced non-small cell lung cancer (NSCLC). The study enrolled subjects in a 1:1 ratio into the experimental group and the control group. Subjects in the experimental group received intrathoracic infusion of M701 after thoracentesis drainage, while subjects in the control group received intrathoracic infusion of cisplatin after thoracentesis drainage. The primary endpoint of the study is puncture-free survival time (Pu FS), defined as the time from the end of treatment to the occurrence of intolerable malignant pleural effusion or death, which is a composite event time endpoint that directly reflects the control time of local treatment for malignant pleural effusion. The secondary endpoints of the study include the objective response rate (ORR) of malignant pleural effusion, time to next puncture (TTNP), symptoms and signs related to malignant pleural effusion, pharmacodynamics, and immunogenicity.

As of March 7, 2025, 54 eligible patients with advanced non-small cell lung cancer (NSCLC) who had progressed after at least one line of systemic treatment and had symptomatic malignant pleural effusion were randomly assigned in a 1:1 ratio, with 26 in the experimental group and 28 in the control group. The median age of the experimental group was 66.5 years, while the median age of the control group was 61.5 years. The proportion of females in the experimental and control groups was 57.7% and 50.0%, respectively. The proportion of patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 was 92.3% and 96.4%, respectively. The proportion of patients with baseline pleural effusion volume of medium or above (≥500mL) was 65.4% and 67.9%, respectively. The proportion of patients who had previously undergone thoracentesis treatment was 65.4% and 71.4%, respectively. The proportion of patients with positive driver gene mutations was 76.9% and 78.6%, respectively. The proportion of patients who had previously received intrathoracic chemotherapy was 42.3% and 35.7%, respectively. Except for the older age of 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, HR (hazard ratio) = 0.80, p = 0.542), while for patients with negative driver gene mutations (median not reached vs. 44.5 days, HR < 0.01, p < 0.001) or those with a history of intrathoracic chemotherapy (median 253 days vs. 72 days, HR = 0.31, p = 0.076), the benefits were more significant. In the aforementioned populations, the objective response rates (MPE ORR) of malignant pleural effusion in the experimental and control groups were 72.7% and 41.7%, respectively After 98 days of random grouping, only the experimental group showed continuous improvement in dyspnea symptoms. Flow cytometry analysis indicated a significant reduction in Ep CAM+CD45- tumor cells in the pleural effusion after M701 infusion, while no such phenomenon was observed in the control group receiving cisplatin.

Safety Results: The incidence of treatment-related adverse events for M701 was 3.7%, compared to 10% in the cisplatin group, with only one serious adverse event (grade 2 fever) related to M701.

Conclusion: Compared to cisplatin, M701 pleural infusion demonstrated significant efficacy in treating malignant pleural effusion and showed good tolerance, supporting its further clinical development, especially for non-small cell lung cancer (NSCLC) patients without driver gene mutations or those who have previously received intrathoracic chemotherapy. This Phase II trial is still ongoing and has shown considerable potential in preventing the recurrence of pleural effusion, particularly in driver gene-negative NSCLC patients or those who have previously undergone intrathoracic chemotherapy. Based on the current excellent results, a pivotal Phase III trial is planned to start in 2026 to validate its efficacy and safety in a large Chinese population