Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 5/2021

Open Access 01-05-2021 | Editorial

Considerations on the Calculation of the Human Equivalent Dose from Toxicology Studies for Biologic Anticancer Agents

Authors: Mohamed Elmeliegy, Chandrasekhar Udata, Ken Liao, Donghua Yin

Published in: Clinical Pharmacokinetics | Issue 5/2021

Login to get access

Excerpt

First-in-human (FIH) clinical trials for investigational anticancer agents are often conducted in cancer patients who are resistant and/or refractory to standard therapy or have no other treatment options that would confer clinically relevant benefit. Selecting an appropriate starting dose for these studies is not only important to ensure patient safety but also to enable efficiency in reaching the therapeutically relevant dose range. Starting with a dose that is too low could lead to a lengthy dose escalation and subjecting many terminally ill cancer patients to subtherapeutic doses [1]. …
Literature
1.
European Medicines Agency. Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products. European Medicines Agency; 2017.
2.
International Conference on Harmonization. Guidance for Industry: S9 Nonclinical Evaluation for Anticancer Pharmaceuticals. International Conference on Harmonization; 2010.
3.
US Food and Drug Administration. Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. US Food and Drug Administration; 2005.
4.
Muller PY, et al. The minimum anticipated biological effect level (MABEL) for selection of first human dose in clinical trials with monoclonal antibodies. Curr Opin Biotechnol. 2009;20(6):722–9.CrossRef
5.
Saber H, et al. An FDA oncology analysis of immune activating products and first-in-human dose selection. Regul Toxicol Pharmacol. 2016;81:448–56.CrossRef
6.
Saber H, et al. An FDA oncology analysis of CD3 bispecific constructs and first-in-human dose selection. Regul Toxicol Pharmacol. 2017;90:144–52.CrossRef
7.
Chapman K, et al. Preclinical development of monoclonal antibodies: considerations for the use of non-human primates. MAbs. 2009;1(5):505–16.CrossRef
8.
Betts A, et al. Linear pharmacokinetic parameters for monoclonal antibodies are similar within a species and across different pharmacological targets: a comparison between human, cynomolgus monkey and hFcRn Tg32 transgenic mouse using a population-modeling approach. MAbs. 2018;10(5):751–64.CrossRef
9.
Oitate M, et al. Prediction of human pharmacokinetics of therapeutic monoclonal antibodies from simple allometry of monkey data. Drug Metab Pharmacokinet. 2011;26(4):423–30.CrossRef
10.
Ling J, et al. Interspecies scaling of therapeutic monoclonal antibodies: initial look. J Clin Pharmacol. 2009;49(12):1382–402.CrossRef
11.
North B, Kocher HM, Sasieni P. A new pragmatic design for dose escalation in phase 1 clinical trials using an adaptive continual reassessment method. BMC Cancer. 2019;19(1):632.CrossRef
Metadata
Title
Considerations on the Calculation of the Human Equivalent Dose from Toxicology Studies for Biologic Anticancer Agents
Authors
Mohamed Elmeliegy
Chandrasekhar Udata
Ken Liao
Donghua Yin
Publication date
01-05-2021
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 5/2021
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-021-00987-2

Other articles of this Issue 5/2021

Clinical Pharmacokinetics 5/2021 Go to the issue

Letter to the Editor

Comment on: "Preterm Physiologically Based Pharmacokinetic Model, Part I and Part II”

Original Research Article

Limited Systemic Exposure with Topical Glycopyrronium Tosylate in Primary Axillary Hyperhidrosis

Original Research Article

Clinical Pharmacokinetics and Bayesian Estimators for the Individual Dose Adjustment of a Generic Formulation of Tacrolimus in Adult Kidney Transplant Recipients

Review Article

Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of Remdesivir, a SARS-CoV-2 Replication Inhibitor

Letter to the Editor

Authors’ Reply to Völler et al: “Comment on: Preterm Physiologically Based Pharmacokinetic Model, Part I and Part II”

Original Research Article

Supra-therapeutic Linezolid Trough Concentrations in Elderly Patients: A Call for Action?