"Evaluating Immuno-Oncology Treatment With PK/PD Modelling "
World Preclinical Congress, Lisbon, 16 Nov 2017
12. Evaluating Immuno-Oncology Treatment With PK/PD Modelling (3-hour short course). World Preclinical Congress Europe (Cambridge Innovation Institute), Sheraton Lisboa Hotel & Spa, Lisbon (11/2017) PDF
• Introduce how translational PK/PD modelling for chemotherapy and cell-directed targeted therapy can be used to relate preclinical data with clinical response
• The basics of PK/PD modelling that are relevant to evaluating novel immuno-oncology treatments
• Learn about dose selection, estimation of therapeutic window, and translational sciences based on PK/PD modelling
Lecture 1. Translational modelling for cell-directed cancer therapies: the successful case studies
The lecture will provide a historical perspective for translational modelling that has been developed for chemotherapies and cancer cell-directed targeted therapies. It will discuss the following topics:
• How do we define the quantitative relationship between preclinical efficacy and clinical activity for this type of treatment?
• What does compelling preclinical evidence entail?
• Is it possible to set minimum preclinical efficacy criteria to qualify a novel treatment for clinical success?
Group exercise 1
• Limitations of the approach/conclusions
• How shall this translational modelling framework be used in practice to best support drug projects?
• Where does it add value?
• Which ideas can be borrowed to support immuno-oncology projects? 1
Lecture 2. The basics of immuno-oncology modelling
This lecture will focus on the basics of immuno-oncology modelling, including:
• Target-mediated drug disposition (TMDD): translating preclinical antibody PK into the clinics
• Target engagement modelling: a MABEL example
Case study: Predict human PK using in vitro and monkey data with Target Mediated Drug Disposition (TMDD) modelling
Case study: First-in-human (FIH) dose finding for bispecific immunomodulatory P-Cadherin LP-DART with mechanistic PK/PD modelling MABEL approach
Group exercise 2
• What are the main gaps from target engagement to disease modulation to (preclinical and clinical) outcome?
• How to fill in these gaps in practice to enable robust clinical translation of preclinical results?