Challenges and Opportunities for Quantitative Clinical Pharmacology in Cancer Immunotherapy: Something Old, Something New, Something Borrowed, and Something Blue
Open accessAbstract
Cancer immunotherapy (CIT) initiates or enhances the host immune response against cancer. Following decades of development, patients with previously few therapeutic options may now benefit from CIT. Although the quantitative clinical pharmacology (qCP) of previous classes of anticancer drugs has matured during this time, application to CIT may not be straightforward since CIT acts via the immune system. Here we discuss where qCP approaches might best borrow or start anew for CIT.
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In cases where RP2D is determined without MTD, clinical PK data and projected efficacious dose based on preclinical studies were the main criteria for choosing an RP2D.
“In these cases, clinical PK data and projected efficacious dose based on preclinical studies were the main criteria for choosing an RP2D.80”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [80]
A PK-based strategy to select nonclinical doses/regimen in mice for approved drugs can maximize the translatability of efficacy results by identifying 'clinically relevant dose' instead of 'maximally tolerated dose'.
“By identifying “clinically relevant dose” instead of “maximally tolerated dose,” this approach can maximize the translatability of efficacy results”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [80]
Frequently, the recommended phase II dose (RP2D) is determined in the absence of a maximum tolerated dose (MTD) for mAbs.
“Frequently, the recommended phase II dose (RP2D) is determined in the absence of a maximum tolerated dose (MTD) for mAbs.”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [80]
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- Authors
- Stroh, M., Carlile, D., Li, C.-C., Wagg, J., Ribba, B., Ramanujan, S., Jin, J., Xu, J., Charoin, J.-E., Xhu, Z.-X., Morcos, P., Davis, J., & Phipps, A.
- Affiliations
- Genentech (US)
- Department of Clinical Pharmacology; F. Hoffmann-La Roche, Roche Innovation Center; Welwyn UK
- F. Hoffmann-La Roche AG (CH)
- Roche Innovation Center New York; New York USA
- Department of Preclinical and Translational PKPD; Genentech; South San Francisco CA USA
- Department of Clinical Pharmacology; Genentech; South San Francisco California USA
- Corresponding author
- Phipps, A
- Venue
- CPT: Pharmacometrics & Systems Pharmacology
- Publisher
- Wiley
- Published
- 2015-09
- Volume
- 4
- Issue
- 9
- Pages
- 495-497
- ISSN
- 2163-8306 (ISSN-L)
- PMC
- PMC4592528
- OpenAlex
- W1828044309
- Cited by
- 16
- References
- 9
- Citations by year
- 2026: 1 · 2022: 1 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 5
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- CPT Pharmacometrics & Systems Pharmacology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- cancer immunotherapy, immune checkpoint inhibitors, pharmacokinetics, pharmacodynamics, immune response, anticancer agents
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