1371P - An anti-EpCAM x CD3 bispecific antibody, M701, for the treatment of malignant pleural effusion in NSCLC patients: Intermediate results of a prospective multicenter phase Ib trial

Background

Malignant pleural effusion (MPE) is a significant complication in patients (pts) with advanced NSCLC, precipitating a pronounced decline in quality of life and severe symptoms, typically attributed to tumor cells disseminate into the pleura, obstruct lymphatic drainage and increase capillary permeability. Talc currently stands as the sole approved medicine for MPE, despite its potential for inducing strong pain and pleurisy.

Methods

Enrolled NSCLC Pts with symptomatic MPE underwent thoracentesis and received intrapleural (IP) infusions of M701. Simultaneously, systemic treatment was administrated as determined by investigators. Primary endpoints included dose limiting toxicities (DLT) and incidence of AEs. Evaluation of MPE efficacy was based on CT-measured pleural fluids volume and the puncture-free survival (PuFS) interval post-M701 treatment. Additional secondary endpoints comprised overall survival (OS) and pharmacokinetics parameters of M701.

Results

As of April 19, 2024, 24 pts were enrolled, with a median age 65 years, 29.2% male, 58.3% harboring EGFR mutation. Median prior lines of treatment were 3. In the dose escalation phase, 11 patients received M701 doses ranging from 25-400 μg on days 1, 4, 7, and 10, while 6 and 7 patients in the dose expansion phase received 4 or 6 doses of M701 every 3 days, respectively. No DLT was reported, with a 16.7% incidence of SAEs, all unrelated to M701. Notably, the only 1 case of ≥grade 3 TRAE was neutropenia. At 4 weeks from enrollment, 61.5% pts in the dose expansion phase had >50% MPE volume decreased (including 2 CR) and successful pleurodesis. The median PuFS of all pts exceeded 129 days, with 14 pts had no re-puncture at the data cutoff. OS data remained immature. Flow cytometry analysis revealed 95% pts had EpCAM+ cells decreased significantly in effusions after the initial 3 M701 infusions.

Conclusions

IP infusion with M701 demonstrates a favorable safety profile and efficacy on preventing the re-accumulation of pleural effusions. And RP2D had been decided (400μg, 4 doses). Data accrual of efficacy and safety parameters within a controlled phase II trial exploring IP infusion of M701 or cisplatin in MPE pts is ongoing.

Clinical trial identification

NCT05543330.

Editorial acknowledgement

Legal entity responsible for the study

Wuhan YZY Biopharma Co., Ltd.

Funding

Wuhan YZY Biopharma Co., Ltd.

Disclosure

P. Zhou: Financial Interests, Personal, Stocks or ownership: Wuhan YZY Biopharma Co., Ltd. S. Huang, M. Pei, L. Huang: Financial Interests, Personal, Full or part-time Employment: Wuhan YZY Biopharma Co., Ltd. All other authors have declared no conflicts of interest.