Targeting TROP2 with DS-1062a: A Promising Approach for Treating Non-Small Cell Lung Cancer and Other Epithelial Tumors

The research abstract discusses the development and evaluation of DS-1062a, an antibody-drug conjugate (ADC) that targets the TROP2 antigen, a protein overexpressed in several epithelial cancers. TROP2's presence in aggressive tumors makes it a promising target for cancer therapy. DS-1062a utilizes Daiichi Sankyo's DXd technology and incorporates a DNA topoisomerase I inhibitor, DXd, to combat cancer cells.

In the study, the in vitro and in vivo effects of DS-1062a were assessed using TROP2-high and -low tumor cell lines and xenograft mouse models. The internalization and intracellular trafficking of DS-1062a were analyzed using immunofluorescence microscopy, revealing co-localization with the lysosomal marker LAMP-2 in TROP2-high tumor cells. The study also evaluated the induction of DNA damage and apoptosis in tumor cells following treatment with DS-1062a.

The results demonstrated that DS-1062a was effective in inhibiting the growth of TROP2-high tumor cells but not TROP2-low cells. The drug showed strong antitumor activity, leading to tumor regression in several TROP2-high tumor models, including non-small cell lung cancer (NSCLC). The accumulation of DXd and DNA damage were observed in TROP2-high tumors treated with DS-1062a, but not in those treated with isotype control IgG ADC.

Pharmacokinetic analysis in the xenograft mouse model indicated favorable profiles for DS-1062a. The study concludes that DS-1062a has the potential to offer a valuable therapeutic option for TROP2-expressing cancers. A phase 1 clinical trial (NCT03401385) is underway to assess the safety and efficacy of DS-1062a in patients with advanced solid tumors.