SKB264 (TROP2-ADC) for the treatment of patients with advanced NSCLC: Efficacy and safety data from a phase 2 study.

作者：Wen‐Feng Fang, Ying Cheng, Zhendong Chen, Wei Wang, Yongmei Yin, Yongsheng Li, Huiting Xu, Xingya Li, Zev A. Wainberg, Guohua Yu, Yanjun Mi, Jordi Rodon Ahnert, Xiang Wang, Xian Wang, Yina Diao, Yalan Yang, Lian Lu, Junyou Ge, Jin Li, Li Zhang · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.16_suppl.9114 · 被引用次数：32 · 研究领域：Lung Cancer Research Studies、Peptidase Inhibition and Analysis、Lung Cancer Treatments and Mutations

9114 Background: TROP2 (trophoblast cell surface antigen 2) is commonly overexpressed in non-small cell lung cancer (NSCLC) and associated with poor prognosis. SKB264 is a novel anti-TROP2 ADC developed using sulfonyl pyrimidine-CL2A-carbonate linker to conjugate its payload, a belotecan-derivative topoisomerase I inhibitor, to achieve an average Drug-to-antibody Ratio (DAR) of 7.4. The design was to achieve a more effective balance between stability in circulation and release of the ADC payload in tumor cells. Here we report clinical efficacy and safety results of SKB264 in the treatment of patients (pts) with NSCLC from a Phase 2 expansion cohort. TROP2 expression level by immunohistochemistry was assessed retrospectively. Correlation analyses between response and TROP2 level will be provided. Methods: This is a Phase 1/2, multicenter dose-escalation/expansion study in pts with relapsed or refractory locally advanced/metastatic NSCLC and other tumor types (NCT04152499). All NSCLC pts received SKB264 at 5 mg/kg IV Q2W. Tumor assessments based on RECIST 1.1 were performed every 8 weeks by investigators. Results: As of February 9 th , 2023, 43 pts (63% male, 88% ECOG PS 1, median age 58 yrs [44-74]) were enrolled. Median follow-up was 11.5 months (mo; 95% CI, 10.4-12.2). Median treatment duration was 5.7 mo (range, 0.5-14.1). Among 39 response-evaluable pts, the ORR was 44% (17/39, 15 confirmed and 2 pending confirmation), median DoR was 9.3 mo (range, 1.3+ to 11.2+), 6-month ...