Presented at AACR Annual Meeting 2024. QSP model simulations were used to predict anti-tumor efficacy and guide dosing of the antibody-drug conjugate Loncastuximab tesirine combined with T cell-dependent bispecific antibodies, Mosunetuzumab or Glofitamab for the treatment of B-cell malignancies.
Engineered T cells, particularly CAR T cells, have revolutionized hematological cancer treatment. However, their complexity poses challenges. This research explores how mathematical models, utilizing clinical data, can elucidate relationships between product characteristics, patient physiology, and clinical outcomes, thereby facilitating the development of next-generation cell therapies.
This study explores Lonca’s efficacy across varying CD19 expression levels, revealing its effectiveness in patients, regardless of low or undetectable CD19 levels by conventional methods. The study integrates quantitative systems pharmacology (QSP) modeling to predict treatment responses, indicating that CD19 expression alone may not predict Lonca’s effectiveness, however, response predictions are improved by considering CD19 surface density.
Presented at ACoP14. Analysis of the QSP model found that the internalization rate of the target receptors may be an important, yet often underestimated, factor for understanding bsAb efficacy in vitro. Simulations of the model indicated that high rates of receptor turnover can increase model predictions of efficacy, particularly at higher antibody concentrations.
ACoP14 pre-meeting workshop. Highlights include exploring Julia as an open source alternative for QSP support of model-informed drug development, gaining insights into IO QSP modeling for antibody drug conjugate (ADCs) and bispecific mAb (bsAb) therapies to drive your own implementations of Project Optimus, and accessing open source Julia versions of two pivotal IO models and parameterizations.
A novel QSP framework integrating PBPK modeling with tumor dynamics was developed using literature and in-house data. By employing a virtual population reflecting patients treated with Lonca, it is possible to evaluate indication, clinical population selection, influence of clinical study covariates, disease phenotypes, and CD19 expression levels on clinical responses
Antibody-drug conjugates (ADCs) are promising anti-cancer drugs but often cause toxicities in clinical use. This poster presents a new model that predicts toxicities of ADCs, including liver and lung effects for drugs like T-DM1 and T-Dxd, and high hepatotoxicity in CM.
As Julia usage continues to grow within regulated biomedical environments, it is vital to ensure analyses are traceable and reproducible. Conducting analyses in an open-science manner is also critical to expand the adoption of Julia and to facilitate the infrastructure growth of Julia as an accessible ecosystem. A step-by-step model-building example of a classic monoclonal antibody-drug conjugate PBPK/tumor dynamics system illustrates how to develop such a reproducible open-science framework.
Ana Ruiz-Garcia, Paul Baverel, Dean Bottino, Michael Dolton, Yan Feng, Ignacio González-García, Jaeyeon Kim, Seth Robey, Indrajeet Singh, David Turner, Shu-Pei Wu, Donghua Yin, Di Zhou, Hao Zhu, Peter Bonate. J Pharmacokinet Pharmacodyn. March, 4 2023
Masato Fukae, Kyle Baron, James Rogers, Ramon Garcia, Masaya Tachibana, John Mondick, Takako Shimizu. Poster presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October – November 2 2022. Poster M-026
Masato Fukae, Kyle Baron, Masaya Tachibana, John Mondick, Takako Shimizu. Poster presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October – November 2 2022. Poster M-030
James A. Rogers, Hugo Maas, Alejandro Peréz. Poster presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October – November 2 2022. Poster T-022
Yin O, Zahir H, French J, Polhamus D, Wang X, Van de Sande M, Tap WD, Gelderblom H, Wagner AJ, Healey JH, Greenberg J, Shuster D, Stacchiotti S. CPT: Pharmacometrics & Systems Pharmacology. 2021; 10: 1422– 1432. doi:10.1002/psp4.12712
Chen J, Ruiz-Garcia A, James LP, et al. Clin Pharmacol Ther. 2021;110(5):1273-1281. doi:10.1002/cpt.2228
Presentation by Jonathan L. French, Sc.D. at 2020 American Conference on Pharmacometrics (ACoP11) virtual meeting. 11 November 2020.
Patel, Chirag, Sanjay Goel, Manish R. Patel, Lakshmi Rangachari, Jayson D. Wilbur, Yaping Shou, Karthik Venkatakrishnan, and A. Craig Lockhart. Clinical Pharmacology in Drug Development, June 2020.
Chia-Chi Lin, Jun Guo, William D. Tap, Andrew J. Wagner, Silvia Stacchiotti, Jih-Hsiang Lee, Xiaoning Wang, Jia Kang, Hamim Zahir, Shun-ichi Sasaki, Ophelia Yin
Poster presented at the 2019 Connective Tissue Oncology Society annual meeting in Toyko, Japan. 14 Nov 2019
Ophelia Yin, Jonathan French, Daniel Polhamus, Hamim Zahir, Michiel van de Sande, William D. Tap, Hans Gelderblom, Andrew J. Wagner, Jon Greenberg, Dale Shuster, Silvia Stacchiotti
Poster presented at 2019 American Conference on Pharmacometrics (ACoP10) in Orlando, FL. 23 October 2019.
Eric Burroughs Jordie, Ahmed Elmokadem, Mohammad Azab, and Aram Oganesian
Presented by Eric Jordie at American Conference on Pharmacometrics 2019.
Ophelia Yin, Jia Kang, William Knebel, Hamim Zahir, Michiel van de Sande, William D. Tap, Hans Gelderblom, Silvia Stacchiotti, Jon Greenberg, Dale Shuster, Andrew J. Wagner
Poster presented at 2019 American Conference on Pharmacometrics (ACoP10) in Orlando, FL. 21 October 2019.
Lu D, Li C, Riggs M, Polhamus D, French J, Agarwal P, Chen S-C, Vadhavkar S, Patre M, Strasak A, Quartino A, Jin JY, Girish S. Cancer Chemother Pharmacol [Internet]. 2019 May 17. doi: 10.1007/s00280-019-03852-z.
Li C, Wang B, Chen SC, Wada R, Lu D, Wang X, Polhamus D, French J, Vadhavkar S, Strasak A, Smitt M, Joshi A, Samant M, Quartino A, Jin J, Girish S. Cancer Chemotherapy and Pharmacology 80 (6): 1079–90. December 2017.
Ocampo-Pelland AS, French JL. Presented at the 8th American Conference on Pharmacometrics (ACoP), Fort Lauderdale, FL, October 2017.
Chen S-C, Quartino A, Polhamus D, Riggs M, French J, Wang X, Vadhavkar S, Smitt M, Hoersch S, Strasak A, Jin JY, Girish S, and Li C. Br J Clin Pharmacol, 2017 Jul 21.
Zomorodi K, Dumas T, Berry S, Johnston C, and Eller M.
Chen SC, Quartino AL, Polhamus D, Riggs MM, French JL, Wang X, Vadhavkar S, Smitt M, Hoersch S, Strasak A, Chernyukhin N, Jin JY, Girish S, Li C. Abstract in Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Cancer Res 2017;77(4 Suppl):Abstract P4-21-26.
Lu D, Li C, Polhamus D, French JL, Riggs MM, Agarwal P, Chen SC, Wang X, Smitt M, Patre M, Strasak A, ChernyukhinN , Quartino AL, Jin JY, Girish S. Presented at the 7th American Conference on Pharmacometrics (ACoP), Bellevue, WA; October 2016.
Polhamus D, French J, Chen SC, Wang B, Li C, Lu D, Girish S, Jin J, Quartino A. Presented at the Annual Meeting of the Population Approach Group in Europe (PAGE), Lisboa, June 2016.
Polhamus D, French J, Chen S-C, Wang B, Li C, Lu D, Girish S, Jin J, Quartino A. Presented at the 6th American Conference on Pharmacometrics, Arlington, VA; October 2015.
Jonathan French. Presented at the 5th American Conference on Pharmacometrics (ACoP), Las Vegas, NV, October 2014.
Hansson EK, Ma G, Amantea MA, French J, Milligan PA, Friberg LE, and Karlsson MO. CPT: Pharmacometrics & Systems Pharmacology. 2013;2(12):e85-. doi:10.1038/psp.2013.62.
Hansson EK, Amantea MA, Westwood P, Milligan PA, Houk BE, French J, Karlsson MO and Friberg LE. CPT: Pharmacometrics & Systems Pharmacology. 2013;2(11):e84-. doi:10.1038/psp.2013.61
Presented at the Annual Meeting of the Population Approach Group Europe (PAGE), Glasgow; June, 2013. Abstract A-06.
French J. Presented at the 4th American Conference on Pharmacometrics (ACoP), Ft. Lauderdale; May 2013.