YZYBIO-B (02496) announced that mid-stage data from its self-developed dual-target bispecific antibody (Bs Ab) M701, targeting epithelial cell adhesion molecule (Ep CAM) and cluster of differentiation 3 (CD3), has been presented in poster form at the 2025 European Society for Medical Oncology (ESMO) conference (poster number: 1880P). This data pertains to a Phase II clinical study conducted in China for treating malignant pleural effusion caused by advanced non-small cell lung cancer (NSCLC). The study is a randomized, controlled, multi-center, open-label Phase II trial (code name: M70103), which enrolled participants in a 1:1 ratio for the treatment and control groups. Participants in the treatment group received intrathoracic infusion of M701 after chest puncture drainage, while those in the control group received intrathoracic infusion of cisplatin. The primary endpoint of the study is puncture-free survival time (Pu FS), defined as the time from the end of treatment to the onset of intolerable malignant pleural effusion or death. This composite endpoint directly reflects the duration of local treatment control over malignant pleural effusion. Secondary endpoints include objective response rate (ORR), time to next puncture (TTNP), related symptoms and signs of malignant pleural effusion, as well as pharmacodynamics and immunogenicity. As of March 7, 2025, a total of 54 eligible patients with symptomatic malignant pleural effusion progressing after at least one line of systemic therapy were randomly assigned to the treatment group (26 patients) and the control group (28 patients). The median age for the treatment group was 66.5 years and 61.5 years for the control group. The proportion of female patients in the treatment and control groups was 57.7% and 50.0%, respectively. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 accounted for 92.3% and 96.4%, and the proportion of patients with baseline pleural effusion volumes of moderate or more (≥500mL) was 65.4% and 67.9%. Additionally, patients who had previously undergone chest puncture therapy accounted for 65.4% and 71.4%, while those with positive driver gene mutations were 76.9% and 78.6%, respectively. Meanwhile, patients with prior intrathoracic chemotherapy comprised 42.3% and 35.7%. Aside from the slightly older age of the treatment group, baseline characteristics were relatively balanced. Efficacy results indicated that the puncture-free survival time in the treatment group was longer than that in the control group (median 130 days versus 85 days, HR=0.80, p=0.542), especially in patients without driver gene mutations (median not reached versus 44.5 days, HR<0.01, p<0.001) or those with a history of intrathoracic chemotherapy (median 253 days versus 72 days, HR=0.31, p=0.076). In these populations, the objective response rates for malignant pleural effusion (MPE ORR) were 72.7% for the treatment group and 41.7% for the control group. After 98 days of random grouping, only the treatment group showed sustained improvement in dyspnea symptoms. Flow cytometry analysis revealed a significant reduction in Ep CAM+CD45- tumor cells in the pleural effusion post-M701 infusion, whereas this was not observed in the cisplatin control group. In terms of safety, the incidence of M701-related adverse events was 3.7%, compared to 10% in the cisplatin group, with only one case of a serious adverse event (grade 2 fever) related to M701. In conclusion, M701 intrathoracic infusion demonstrated significant efficacy compared to cisplatin in treating malignant pleural effusion, with good tolerability, providing support for further clinical development, particularly for non-small cell lung cancer (NSCLC) patients without driver gene mutations or those with prior intrathoracic chemotherapy. This Phase II trial is ongoing and has shown considerable potential in preventing pleural effusion recurrence, especially in non-small cell lung cancer (NSCLC) patients without driver gene mutations or those with a history of intrathoracic chemotherapy. Based on these promising results, a pivotal Phase III trial is planned to launch in 2026 to validate its efficacy and safety in a large population in China.