ZL-1310, a DLL3 ADC, in patients with extensive stage small cell lung cancer: Ph1 trial update.

作者：Manish Patel, Yi‐Long Wu, Zhen Wang, Pedro Rocha, Qiming Wang, Yingying Du, Grace K. Dy, Afshin Dowlati, A.I. Spira, Xiaorong Dong, Martin Gutierrez, Yuping Sun, Haiyong Wang, Wenxiu Yao, Luis Paz‐Ares, Yinjia Fu, Xiao Liu, Xiao Wang, Renke Zhou, Jun Zhao · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.3041 · 被引用次数：16 · 研究领域：Lung Cancer Research Studies、Cancer therapeutics and mechanisms、Peptidase Inhibition and Analysis

3041 Background: Treatment options are limited for patients (pts) with extensive-stage small cell lung cancer (ES-SCLC) that progress after platinum-based chemotherapy (chemo). ZL-1310, a DLL3-targeted antibody drug conjugate (ADC) with a topoisomerase 1 inhibitor payload and cleavable linker, demonstrated promising preliminary results in pts with relapsed/refractory (r/r) ES-SCLC (Spira et al, ENA 2024). Here, we report updated data with additional pts and follow-up (NCT06179069). Methods: This is a two-part Phase I study of ZL-1310 administered intravenously every 3 weeks to pts with r/r SCLC who have progressed after at least one platinum-based chemo regimen. Part 1A is a monotherapy dose escalation; Part 2 is a randomized dose optimization/expansion. Study endpoints include safety parameters, objective response rate (ORR) per RECIST v1.1, duration of response (DOR), disease control rate (DCR) and pharmacokinetics (PK). Exploratory tumor biomarkers, including DLL3 expression (expressed as H-score), are examined. Results: As of 28 Jan 2025, 28 pts were enrolled in the dose escalation Part 1A and received ZL-1310 at dose levels ranging from 0.8 mg/kg to 2.8 mg/kg. The median time on study is 5.1 months (range 2.4-10.1+). Median age was 66 years (range 36-79); 43% were female; 75% had an ECOG performance status of 1; 93% progressed after prior anti-PD-L1 therapy; 39% had prior lung irradiation, and 36% had baseline brain metastases. Any-grade treatment-related adverse events ...