Model-based meta-analysis (MBMA) of non-small cell lung cancer with PD-(L)1 inhibitors for early development decision making and late phase efficacy benchmarking
David Turner, PhD, Distinguished Scientist
David Turner is currently a Distinguished Scientist in the Department of Clinical Pharmacology at Genentech, since September 2021. He has over ten years of experience in Clinical Pharmacology and Modeling and Simulation, contributing to various global regulatory submissions and health authority interactions. At Merck, he was part of the Clinical Pharmacology team working on pembrolizumab approvals in melanoma and metastatic NSCLC, which has since become a standard of care in these settings.
Before joining Genentech, David worked at GSK as a clinical pharmacology lead for oncology programs, where he helped develop MBMA methods to compare internal and external oncology treatments. At Genentech, he is involved as a Clin Pharm lead with the mosunetuzumab (bispecific anti-CD20/CD3) program, assisting in its initial regulatory submissions and approvals for relapsed/refractory follicular lymphoma.
David has authored over 40 publications, delivered four oral presentations, and presented more than 20 conference posters. His research on exposure-response confounding has been recognized for its influence on the field and dose selection practice for biologic treatments.
Joseph Chen, PharmD, Senior Principal Scientist
Joseph Chen is a Senior Principal Scientist in the Genentech Clinical Pharmacology, Oncology group, supporting large molecule oncology drug development including atezolizumab (anti-PD-L1 mAb). Prior to joining Genentech, he worked as a clinical pharmacologist at Pfizer, supporting small molecule oncology drug development, including Lorbrena, an approved ALK-inhibitor small molecule TKI in NSCLC. He received his PharmD at the UCSD Skaggs School of Pharmacy in 2016.
Russ Wada, Principal Consultant, QuanTx Consulting
QuanTx Consulting is a QCP consulting services company with focus on pharmacometrics, located in Mountain View CA. Russ Wada is the Founder and a Principal Consultant at QuanTx Consulting. Previously Russ worked at Pharsight, Quantitative Solutions, and Certara. He has over 25 years of experience as a modeling and simulation consultant in drug development. He received his PhD in Engineering from UCLA and did a postdoctoral fellowship in Clinical Pharmacology in the Dept of Anesthesiology at Stanford.
In this presentation, we will discuss the development and application of a model-based meta-analysis (MBMA) framework designed to evaluate the efficacy of treatments in metastatic non-small cell lung cancer (mNSCLC). The framework was created to facilitate decision-making in early-phase oncology trials by enabling indirect comparisons of single-arm trials with external data. Utilizing data from 15 studies on PD-1 inhibitors pembrolizumab and nivolumab, we developed models to predict overall response rate (ORR) and overall survival (OS), accounting for key covariates such as tumor histology, treatment type, and PD-L1 expression levels.
Our analysis quantified associations between patient characteristics and treatment efficacy, demonstrating the potential of our MBMA framework to support go/no-go decisions and improve early-phase clinical trial designs. By simulating hypothetical scenarios, one can forecast OS outcomes based on ORR, providing insights into the likely success of novel treatment regimens. This work highlights the utility of MBMA in interpreting clinical trial data and guiding drug development in oncology.
Citations: Turner DC, Wada R, Zhou H, Wang X, de Greef R, Valiathan C, Zhang L, Zhang N, Kuchimanchi M, Chen TT, Ballas M, Visser SAG. Model-based meta-analysis of non-small cell lung cancer with standard of care PD-1 inhibitors and chemotherapy for early development decision making. CPT Pharmacometrics Syst Pharmacol. 2023 Nov;12(11):1751-1763. doi: 10.1002/psp4.12917. Epub 2023 Jan 31. PMID: 36642813; PMCID: PMC10681483.