Assessment of efficacy of LBL-024, a novel and uniquely designed bispecific antibody against PD-L1 and 4-1BB, combined with etoposide/platinum-based chemotherapy in treatment-naive advanced extrapulmonary neuroendocrine carcinoma (EP-NEC): A multicenter phase Ib/II trial.

作者：Ming Lü, Panpan Zhang, Bo Liu, Yuping Sun, Ning Li, Shegan Gao, Yanqiao Zhang, Jianwei Yang, Mudan Yang, Hongming Pan, Ji Ma, Peng Zhao, Wenduo He, Shengli Cai, Lin Shen · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.2500 · 被引用次数：1 · 研究领域：Neuroendocrine Tumor Research Advances、Lung Cancer Research Studies、Gyrotron and Vacuum Electronics Research

2500 Background: The prognosis for patients with EP-NEC is very poor. A recognized 1L treatment for advanced disease is etoposide/platinum-based chemotherapy with no standard 2L/3L treatment. LBL-024 blocks the immunosuppressive pathway of tumor cells by targeting PD-L1 and effectively co-stimulates T cells by targeting 4-1BB, to improve the anti-tumor immune response. Here we report the safety and efficacy of LBL-024 combined with etoposide and cisplatin or carboplatin (EP/EC) as first line treatment in patients with advanced NEC. (NCT06157827). Methods: This is a phase Ib dose escalation and phase II dose optimization/expansion clinical trial. Phase Ⅰb enrolled previously untreated advanced EP-NEC and SCLC patients, phase Ⅱ enrolled previously untreated advanced EP-NEC patients. Three dose levels of LBL-024 (6, 10 and 15 mg/kg, i.v. Q3W) plus EP/EC in phase Ib were evaluated, 2 dose levels (6 and 15 mg/kg, i.v. Q3W) of LBL-024 plus EP/EC were evaluated in a randomized dose optimization. The primary endpoints were tolerability, safety, efficacy (RECIST 1.1) and RP2D, the secondary endpoints were PK, PD and ADA. Results: As of December 26, 2024, a total of 53 patients were enrolled, with 13 patients in Phase Ib and 40 patients in dose optimization stage of Phase II. Phase Ib included 2 patients with SCLC, 1 with MiNEN, and 10 with EP-NEC. All 40 patients in Phase II were EP-NEC. During the Dose escalation stage, no DLTs were observed. During the Dose optimization stage, 15 mg...