Histology-agnostic approvals for antibody-drug conjugates in solid tumours: is the time ripe?

Several antibody-drug conjugates (ADCs) have been recently approved to treat solid tumours. Since ADCs seem to have activity in multiple malignancies sharing the expression of a specific antigen, they may be mirroring the experience of histology-agnostic-targeted treatments. So, the possibility to interpret the activity of some ADCs across different cancer types in a biomarker-driven perspective arises. However, relevant biological, methodological, and regulatory challenges should be highlighted and addressed, in order to grant ADCs biomarker-driven regulatory approvals in the next future. In this review, we discuss challenges and opportunities posed by the pan-histological expansion of ADCs in solid tumours. In particular, we provide an overview about technological and manufacturing advancements; we offer up-to-date highlights of the current evidence from clinical trials investigating ADCs in solid tumours; we discuss the need for the identification of optimal predictive biomarkers, as well as major methodological, statistical, and regulatory considerations for a biomarker-driven histology-agnostic approach. (C) 2022 Elsevier Ltd. All rights reserved.

Automated summary

This review discusses the challenges and opportunities of pan-histological expansion of ADCs in solid tumors. It covers technological and manufacturing advancements, current evidence from clinical trials, and the need for predictive biomarkers and methodological, statistical, and regulatory considerations in a biomarker-driven histology-agnostic approach.