First report of efficacy and safety results from a phase 2 trial evaluating BNT327/PM8002 plus chemotherapy (chemo) as first-line treatment (1L) in unresectable malignant mesothelioma.

作者：Ying Cheng, Liqin Lu, Wu Zhuang, Dongyuan Zhu, Yanqiu Zhao, Na Li, Yubiao Guo, Zhouguang Hui, Yan Li, Ziping Wang, Peng Zhang, Yan Wang · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.8511 · 被引用次数：5 · 研究领域：Occupational and environmental lung diseases

8511 Background: Malignant mesothelioma is a rare neoplasm with a high unmet medical need. BNT327 is an investigational bispecific antibody, targeting both PD-L1 and VEGF-A in the tumor and tumor microenvironment (TME). By binding to PD-L1 on tumor cells it is designed to restore effector T-cell function and by binding to VEGF-A within the TME it also reverses the negative impact of VEGF signaling on immune cell infiltration and activation. In addition, via VEGF-A neutralization, it normalizes tumor vasculature. This dual targeting of PD-L1 and VEGF-A aims to deliver better efficacy and safety. BNT327 has shown encouraging preliminary activity in thoracic malignancies incl. SCLC (ESMO 2023) and NSCLC (ASCO & ESMO 2024). Methods: After a safety run-in (n=6), this ongoing, multicenter, single-arm phase 2 clinical trial recruited chemo naive pts (pts) aged ≥18 yrs with unresectable malignant mesothelioma (pleural (MPM) or peritoneal (MPeM)) to evaluate BNT327 30 mg/kg Q3W IV combined with 4-6 cycles pemetrexed and platinum, followed by BNT327 maintenance. Primary endpoints were efficacy (ORR per RECIST 1.1 for MPeM, mRECIST 1.1 for MPM) and safety (CTCAE V5.0). Results: As of 25 Oct 2023, 31 pts, median age 58 yrs (range 43-71), 80.6% ECOG PS 1 and 83.9% with metastatic disease had been enrolled, of which 23 had MPM and 8 MPeM. At the cutoff date of 20 Dec 2024, the median exposure duration was 16.0 mo (95% CI 8.1, 19.5) and median follow-up time 19.3 mo (95% CI 17.3, 20.9)....