Challenges in characterizing treatment response in oncology - Pitfalls and solutions

Recorded On: 11/13/2024

Session Description

Description: The session aims to focus on some of the challenges to characterize treatment responses in oncology. Characterizing the treatment response in general and exposure-response in particular is essential for approval of new drugs. The relevance of this topic is highlighted by FDAs Project Optimus. Survival metrics in many recent oncology studies demonstrate clear signs of non-proportional hazards (NPH). This violates the proportional hazard assumption of the traditional log-rank and Cox proportional hazard tests. Although a wide range of parametric and non-parametric methods for NPH has been proposed, there is no consensus on the best approaches. Prof. Hooker and colleagues have been involved in a project sponsored by the European Medicines Agency to address this. Over the past two decades, antibody-drug conjugates (ADCs) have emerged as an important new class of drugs in oncology. Compared with traditional chemotherapy, ADCs combine the target specificity of antibodies with chemotherapeutic capabilities of cytotoxic drugs. The aim is to widen the therapeutic window for the cytotoxic drugs and be able to achieve higher on target concentrations with less of target toxicity. However, efficient dose optimization remains an essential challenge to fully benefit from the advantages with ADCs. Joint models for longitudinal biomarker response and survival metrics have been shown to be a valuable approach to accurately capture how time dependent patient conditions affect survival. More traditional sequential modeling approaches can be biased due to factors such as immortal time bias and shrinkage of empirical bayes estimates.

Conference Date

November 10-13, 2024

Conference Location

Phoenix, Arizona, USA

DOI

10.70534/JBZC8922

Andrew Hooker, PhD, ISOP member

Professor of Pharmacometrics

Uppsala University

Andrew C. Hooker, PhD, is a Professor of Pharmacometrics at Uppsala University, Sweden. Andrew received a BS in Physics with a Mathematics Minor at the University of Colorado and received a Masters and then a PhD in Bioengineering from the University of Washington, Seattle. Andrew joined the faculty at Uppsala University in 2006. His research ranges between methodological and applied pharmacometrics, including: optimal (adaptive) experimental design, methodological problems associated with building, evaluating and using pharmacometric models (including using models for bioequivalence evaluation) and the development and use of PKPD models in a range of therapeutic areas and drug classes. Andrew is a co-developer of a number of software programs including Xpose, PsN, Pharmpy and the optimal design program PopED. Andrew has published over 90 papers in peer reviewed journals, supervised 12 students to their PhD degree and mentored 11 post-docs. In 2012, he co-founded the model-informed drug development consultancy company Pharmetheus.

Tushar Garimella, PhD, ISoP member, ACCP member

Executive Director, Quantitative Clinical Pharmacology

Daiichi Sankyo Inc

Antoine Pitoy, PhD student

PhD Student

INSERM / Université Paris Cité

Antoine graduated from Sorbonne Université with a master’s degree in public health with a specialization in biostatistics and modeling. Antoine started a PhD at Université Paris Cité, under the supervision of Dr. Julie Bertrand within the INSERM IAME research team and in collaboration with Sanofi. Antoine’s work explores the potential of joint modeling to support decision-making in oncology drug development

Martin Bergstrand

Principal Consultant and MIDD Platform Science Lead

Pharmetheus

Martin obtained his PhD in Pharmacometrics from Uppsala University. He has 20+ years of drug development experience in areas such as metabolic disorders, autoimmune disease, infectious disease, hematological disorders etc. In 2012 Martin co-founded the consulting company Pharmetheus AB. In the consultant role he has been engaged as strategic advisor on behalf of multiple clients and acted as the main responsible consultant for 50+ pharmacometric data analysis projects on behalf of more than 20 different clients. The projects have ranged from pre-clinical translational projects to submission ready large-scale phase III PKPD analysis. These analyses have among other things contributed to 5+ successful NDA filings.

Pavan Vaddady, PhD

Executive Director, QP2 Oncology

Merck & Co., Inc.

Pavan Vaddady currently serves as an Executive Director, Quantitative Pharmacology & Pharmacometrics - Oncology at Merck & Co., Inc., where he leads a team responsible for advancing Merck’s oncology portfolio efficiently across different milestones from first in human through registration. During his career, he led several early and late-stage development programs across multiple therapeutic areas both as a clinical pharmacologist and a pharmacometrician and applied model informed approaches to impact key drug discovery and development decisions. Prior to his current role, he was the Head of Advanced Pharmacometrics, Quantitative Clinical Pharmacology at Daiichi Sankyo, Inc., where he led a global team of scientists working on pharmacometrics deliverables for submissions along with advanced modeling projects involving multiple oncology assets. Pavan is passionate about teaching and mentoring and currently holds the position of Adjunct Professor at the University of Tennessee Health Science Center. He is also an elected Member of the Board of Trustees at the International Society of Pharmacometrics (ISoP), a non-profit organization dedicated to the advancement and promotion of pharmacometrics globally. He obtained his B. Pharm. (Hons.), and M. Pharm. from BITS Pilani, India and his Ph.D. in Pharmaceutical Sciences from the University of Tennessee Health Science Center, Memphis, USA.

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