While the classic chemotherapy agents are cytotoxics, which do not have specific target, the new approach in oncology drug development is focused on immunotherapy, where the new compounds target specific molecular targets. 

But what are the challenges in immuno-oncology drug development?

  • Unlike classic cytotoxics immunotherapy requires specific patient population, which is selected based on strong biological rational and predictive biomarkers. However, the data that is available currently regarding biomarkers is very limited.
  • Different tumour types respond in a different way to immunotherapy. Tumour heterogeneity is another challenge.
  • Because these new immunotherapy agents have new mechanisms of action it is critical to select carefully the endpoints. Failure to do so may give false inefficacy results in early stage.
  • Standard radiology assessments of tumour response (such as widely used RECIST criteria) may not be the best to evaluate these new agents. This led to the development of new assessments: Choi criteria, mRECIST and PERCIST. Proper evaluation of the tumour response is important not only to avoid exposing patients on unnecessary toxicity if the treatment is not efficient in them but also continue treatment for patients who benefit from the treatment and have had pseudo-progression.
  • New toxicity profiles – there are new toxicity associated with the immunotherapy, which are still unknown – for example, sepsis, autoimmune reactions, etc. Often such toxicities were not detected in preclinical research.
  • Optimal dose could be different in immunotherapy – the new agents have different mechanisms of action and lower doses could trigger the required response. The classic concept of dose was to be administrated the highest possible dose, which does not trigger unacceptable toxicity. 

The new challenges that the immuno-oncology establish require new designs of the clinical trials, which will take into consideration the complexity of the new treatment agents and the therapeutic area.

Source: Immuno-Oncology: The Third Paradigm in Early Drug Development

Author: Olga Peycheva

Olga is a clinical research professional who has been working in clinical research since 2005. She has extensive experience in clinical research in Eastern and Western Europe. 

Originally published on 2 Aug 2017