An open-label, multicenter phase 1 study to characterize safety, tolerability, preliminary antitumor activity, and pharmacokinetics of VIP236 monotherapy in patients with advanced cancer.

摘要: TPS3168Background: VIP236, a first-in-class SMDC, consists of an αvβ3 integrin small molecule binder, a peptide linker cleaved by neutrophil elastase (NE) in the tumor microenvironment (TME), and a camptothecin (CPT) payload VIP126 which was optimized for high permeability and low efflux. The overall drug design strategy for VIP236 is targeted delivery to the TME and tumors expressing αVβ3 integrin on their cell surface with release of the optimized CPT derivative by NE also present in the TME. VIP126, when delivered as a component of VIP236, is anticipated to kill tumor cells while reducing effects to normal tissue. VIP236 exhibits convincing single agent in vivo antitumor efficacy and acceptable tolerability in multiple human tumor cell line- and patient- derived xenograft models in mice, including breast, colorectal, small cell lung, gastric, metastatic breast and metastatic colon cancer. In three gastric cancer …