Abstract 5391: Antibody-drug conjugates in oncology drug development: Examining approaches to set the first-in-human dose

2012 ◽  
Author(s):  
Nadine N. Bewry
Keyword(s):  
Drug Development ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Oncology Drug ◽  
Human Dose ◽  
Oncology Drug Development ◽  
Antibody Drug

scholarly journals Interspecies Scaling of Antibody–Drug Conjugates (ADC) for the Prediction of Human Clearance

Antibodies ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 1
Author(s):  
Iftekhar Mahmood
Keyword(s):  
Prediction Error ◽  
Animal Species ◽  
Allometric Scaling ◽  
Pharmacokinetic Parameters ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Human Dose ◽  
Animal Data ◽  
Fold Prediction ◽  
Antibody Drug

Allometric scaling is a useful tool for the extrapolation of pharmacokinetic parameters from animals to humans. The objective of this study was to predict human clearance of antibody–drug conjugates (ADC) allometrically from one to three animal species and compare the predicted human clearance with the observed human clearance. For three animal species allometric scaling, the “Rule of Exponents” (ROE) was used. The results of the study indicated that three-species allometric scaling in association with the ROE provides acceptable prediction (within 0.5–2-fold prediction error) of human clearance. The two-species allometric scaling resulted in substantial prediction error. One-species scaling using a fixed exponent of 1.0 provided acceptable prediction error (within 0.5–2-fold) by monkey, rat, and mouse, in which monkey and rat were comparable. Overall, the predicted human clearance values of ADCs from animal(s) was good. The allometric method proposed in this article can be used to predict human clearance from the animal data and subsequently to select the first-in-human dose of ADCs.

ASCO-GU 2019: Metastasierte Urothelkarzinome

2019 ◽  
Vol 10 (03) ◽  
pp. 140-141
Author(s):  
Alexander Kretzschmar
Keyword(s):  
San Francisco ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Chapel Hill ◽  
Antibody Drug

Die Therapielandschaft des metastasierten Urothelkarzinoms hat sich seit der Zulassung der ersten Immun-Checkpoint-Inhibitoren verändert. Die neuen Therapien sind deutlich effektiver, allerdings erreichen die Responseraten der neuen Therapien nur bis zu etwa 30 %, beklagte Prof. Matthew Milowsky, Chapel Hill/USA, auf einer Oral Abstract Session auf dem ASCO-GU. In San Francisco gaben erste Vorträge und Poster bereits einen Einblick, wovon diejenigen Patienten profitieren könnten, die auf die etablierten Chemotherapien und die neuen Immuntherapien nicht ansprechen. Manche Onkologen sprechen bereits von der „Post-Checkpoint-Ära”. Als Kandidaten werden vor allem Antikörper-Wirkstoff-Konjugate (antibody-drug conjugates; ADC) gehandelt – und zwar nicht nur zur Therapie des metastasierten Blasenkarzinoms.

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