Histology-agnostic approvals for antibody-drug conjugates in solid tumours: is the time ripe?
Chiara Corti1, Gabriele Antonarelli1, Carmine Valenza1
1Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Haematology (DIPO), University of Milan, Milan, Italy.
Abstract:
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.
Insights
Antibody-drug conjugates (ADCs) show promise across various solid tumors by targeting shared antigens. Addressing biological, methodological, and regulatory hurdles is key for biomarker-driven, histology-agnostic approvals.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Several antibody-drug conjugates (ADCs) are approved for solid tumors.
- ADCs may exhibit activity across multiple cancer types expressing specific antigens, similar to targeted therapies.
- This suggests a potential for biomarker-driven, histology-agnostic approaches.
Purpose of the Study:
- To review the challenges and opportunities of expanding antibody-drug conjugate (ADC) use across different tumor types (pan-histological).
- To discuss advancements in ADC technology, manufacturing, and clinical trial evidence.
- To highlight the need for predictive biomarkers and address regulatory considerations for histology-agnostic approvals.
Main Methods:
- Literature review of recent advancements in ADC technology and manufacturing.
- Analysis of current clinical trial data for ADCs in solid tumors.
- Discussion of biological, methodological, statistical, and regulatory aspects of biomarker-driven approaches.
Main Results:
- Technological and manufacturing advancements are enabling wider ADC applications.
- Clinical trials show promising ADC activity in various solid tumors.
- Identification of predictive biomarkers and robust regulatory frameworks are crucial.
Conclusions:
- The pan-histological expansion of ADCs in solid tumors presents significant opportunities.
- Overcoming biological, methodological, and regulatory challenges is essential for future biomarker-driven approvals.
- A collaborative approach is needed to realize the full potential of ADCs across diverse malignancies.
