超过 50 种结构形式多样的双特异性抗体正在肿瘤临床开发中，针对多种免疫和肿瘤靶点。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.
Our Speakers
Piet van der Graaf, 高级副总裁兼定量系统药理学负责人
Piet 曾任职于赛诺菲和辉瑞，在制药行业拥有 20 多年经验，为 QSP 项目带来了丰富的技能和经验，并为 Certara 的战略发展做出了贡献。他还任 《CPT：定量药理学与系统药理学》的总编辑。
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.
