SKB264 ADC: A first-in-human study of SKB264 in patients with locally advanced unresectable/metastatic solid tumors who are refractory to available standard therapies.

作者：Yongheng Liu, Wei Lian, Xi Zhao, Yina Diao, Jian Xu, Xiao Liang, Qing Yan, Tongtong Xue, Jingyi Wang · 发表于：Journal of Clinical Oncology · 年份：2020 · DOI：10.1200/jco.2020.38.15_suppl.tps3659 · 被引用次数：21 · 研究领域：Radiopharmaceutical Chemistry and Applications、HER2/EGFR in Cancer Research、Peptidase Inhibition and Analysis

TPS3659 Background: Elevated expression of trophoblast antigen 2 (TROP2) is often associated with invasion/aggression, progression, and metastasis of many different tumor types. Efficacies of anti-TROP2 ADC have been demonstrated both pre-clinically and in the clinical trials. SKB264 is being developed as a further optimized TROP2-targeting ADC with a proprietary cytotoxic, belotecan-derived payload and novel stable conjugation chemistry to achieve average DAR (Drug Antibody Ratio) of 7.4. Release of payload upon SKB264 internalization is in a TROP2 expression dependent manner. Extensive preclinical studies demonstrated antitumor activity of SKB264 in vitro, in xenograft and patient-derived xenograft (PDX) animal models. In addition, safety studies have demonstrated a good safety profile to allow SKB264 to be studied in clinical trials. Methods: SKB264-01 is a global open label multicenter study. The study is divided into 2 parts, the phase I is to determine the safety profile, define MTD and/or the RP2D, and characterize DLTs of SKB264. Dose escalation and MTD identification will be directed using a Bayesian logistic regression model (BLRM) with overdose control. The phase II is to evaluate efficacy and obtain clinical activity data of SKB264 as a monotherapeutic agent at the RP2D in each of the designated Phase II cohorts and overall (n = 16 per cohort; n = 48 for entire Phase II part). Objective response rate (ORR) will be continuously evaluated in each cohort using a Baye...