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Published on: August 15, 2019
Considerations for the clinical development of immuno-oncology agents in cancer
Atanasio Pandiella1,2, Emiliano Calvo3, Victor Moreno4
1Centro de Investigación del Cáncer, CIC-CSIC, Salamanca, Spain.
Abstract:
Targeting of the immune system has shown to be a successful therapeutic approach in cancer, with the development of check point inhibitors (ICI) or T-cell engagers (TCE). As immuno-oncology agents modulate the immune system to attack cancer cells and do not act directly on oncogenic vulnerabilities, specific characteristics of these compounds should be taken in consideration during clinical development. In this review we will discuss relevant concepts including limitations of preclinical models, special pharmacologic boundaries, clinical development strategies such as the selection of clinical indication, line of treatment and backbone partner, as well as the endpoints and expected magnitude of benefit required at different stages of the drug development. In addition, future directions for early and late trial designs will be reviewed. Examples from approved drugs or those currently in clinical development will be discussed and options to overcome these limitations will be provided.
Insights
Immuno-oncology agents like checkpoint inhibitors and T-cell engagers offer successful cancer therapy. This review covers their unique clinical development, from preclinical models to trial designs and overcoming limitations.
Area of Science:
- Oncology
- Immunology
- Clinical Pharmacology
Background:
- Immunotherapy, including immune checkpoint inhibitors (ICI) and T-cell engagers (TCE), is a successful cancer treatment strategy.
- Unlike traditional therapies, immuno-oncology agents leverage the immune system, necessitating unique development considerations.
Purpose of the Study:
- To review key aspects of clinical development for immuno-oncology agents.
- To discuss limitations, strategies, and future directions for optimizing drug development in this field.
Main Methods:
- Literature review of immuno-oncology drug development.
- Analysis of preclinical models, pharmacologic properties, and clinical trial strategies.
- Examination of endpoints, magnitude of benefit, and trial designs.
Main Results:
- Identified limitations in preclinical models and pharmacologic boundaries.
- Outlined clinical development strategies including indication selection, treatment lines, and backbone partners.
- Discussed required endpoints and benefit magnitude for different development stages.
Conclusions:
- Successful clinical development of immuno-oncology agents requires careful consideration of unique properties and strategic planning.
- Addressing limitations in preclinical models and trial design is crucial for advancing novel immunotherapies.
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