More than 50 bispecific antibodies are in oncology clinical development with a large diversity in formats, directed at a range of immune and tumor targets. Bispecifics have demonstrated the potential for enhanced efficacy and reduced systemic toxicity. However, they are complex modalities with challenges to overcome in early clinical trials, including selection of relevant starting doses and dose escalation strategy due to non-intuitive exposure-response relationships. In this context, prediction and management of cytokine-release syndrome (CRS) is important.
Multiple factors can contribute to between-patient variability, including tumor type, avidity, receptor expression, effector-to-target-cell ratio, and presence of soluble target.
Mechanistic, quantitative systems pharmacology (QSP) models are increasingly being used in the design of bispecifics and to guide translation research, clinical trial design, dose regimen optimization, and patient selection.
Following a general introduction, we shared a case study on using model-informed clinical development to unlock the therapeutic potential of mosunetuzumab (a CD20/CD3 bispecific antibody) to illustrate the application of QSP in drug development and regulatory decision-making.
Piet van der Graaf, Senior Vice President, Quantitative Systems Pharmacology
With over 20 years of experience working in the pharmaceutical industry at Sanofi and Pfizer, Piet brings considerable skill and experience to QSP projects and contributes to the strategic development of Certara. He is also Editor-in-Chief of CPT: Pharmacometrics & Systems Pharmacology.
Chi-Chung Li, Principal Scientist at Genentech
Chi has 13 years in clinical drug development experience and specializes in quantitative clinical pharmacology of small molecule pharmaceuticals and biologics. She supported development of molecules across a broad spectrum of therapeutic areas including cancer immunology, neuroscience, infectious disease, cardiovascular diseases, and respiratory/immunology. She joined Genentech in 2014 and has served as the clinical pharmacology lead of several immuno-oncology molecules, including atezolizumab, anti-OX40, personalized cancer vaccine, and mosunetuzumab (aCD20/CD3 bispecific antibody). She currently leads the Immune Cell Bispecifics platform strategy in Clinical Pharmacology at Genentech. She is passionate in promoting science-driven drug development to maximize benefit-risk of therapeutic modalities and accelerate/enhance access to anti-cancer therapies.