scholarly journals Clinical Pharmacology of Antibody-Drug Conjugates

Antibodies ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 20
Author(s):  
Iftekhar Mahmood
Keyword(s):  
Clinical Pharmacology ◽  
Patient Population ◽  
Inflammatory Diseases ◽  
Biologically Active ◽  
Myelogenous Leukemia ◽  
Optimum Dose ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Selection Of ◽  
Antibody Drug

Antibody-drug conjugates (ADCs) are biopharmaceutical products where a monoclonal antibody is linked to a biologically active drug (a small molecule) forming a conjugate. Since the approval of first ADC (Gemtuzumab ozogamicin (trade name: Mylotarg)) for the treatment of CD33-positive acute myelogenous leukemia, several ADCs have been developed for the treatment of cancer. The goal of an ADC as a cancer agent is to release the cytotoxic drug to kill the tumor cells without harming the normal or healthy cells. With time, it is being realized that ADCS can also be used to manage or cure other diseases such as inflammatory diseases, atherosclerosis, and bacteremia and some research in this direction is ongoing. The focus of this review is on the clinical pharmacology aspects of ADC development. From the selection of an appropriate antibody to the finished product, the entire process of the development of an ADC is a difficult and challenging task. Clinical pharmacology is one of the most important tools of drug development since this tool helps in finding the optimum dose of a product, thus preserving the safety and efficacy of the product in a patient population. Unlike other small or large molecules where only one moiety and/or metabolite(s) is generally measured for the pharmacokinetic profiling, there are several moieties that need to be measured for characterizing the PK profiles of an ADC. Therefore, knowledge and understanding of clinical pharmacology of ADCs is vital for the selection of a safe and efficacious dose in a patient population.

Regulatory considerations for clinical pharmacology during development of antibody-drug conjugates.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 2569-2569 ◽  
Author(s):  
Stacy Shifflett Shord ◽  
Sarah J Schrieber ◽  
Hong Zhao ◽  
Brian Booth ◽  
Nam Atiqur Rahman
Keyword(s):  
Clinical Pharmacology ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

scholarly journals Clinical pharmacology of vc-MMAE antibody–drug conjugates in cancer patients: learning from eight first-in-human Phase 1 studies

mAbs ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 1699768 ◽  
Author(s):  
Chunze Li ◽  
Cindy Zhang ◽  
Zao Li ◽  
Divya Samineni ◽  
Dan Lu ◽  
...  
Keyword(s):  
Clinical Pharmacology ◽  
Cancer Patients ◽  
Phase 1 ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

scholarly journals Clinical pharmacology strategies in supporting drug development and approval of antibody–drug conjugates in oncology

2021 ◽  
Author(s):  
Stephanie N. Liu ◽  
Chunze Li
Keyword(s):  
Clinical Pharmacology ◽  
Complex Structure ◽  
Clinical Development ◽  
Cytotoxic Drug ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Technology Heterogeneity ◽  
Quantitative Understanding ◽  
Small Molecule Therapeutics ◽  
Antibody Drug

AbstractAntibody–drug conjugates (ADCs) are important molecular entities in the treatment of cancer. These conjugates combine the target specificity of monoclonal antibodies with the potent anti-cancer activity of small-molecule therapeutics. The complex structure of ADCs poses unique challenges to characterize the drug’s pharmacokinetics (PKs) and pharmacodynamics (PDs) since it requires a quantitative understanding of the PK and PD properties of multiple different molecular species (e.g., ADC conjugate, total antibody and unconjugated cytotoxic drug). As a result, clinical pharmacology strategy of an ADC is rather unique and dependent on the linker/cytotoxic drug technology, heterogeneity of the ADC, PK and safety/efficacy profile of the specific ADC in clinical development. In this review, we summarize the clinical pharmacology strategies in supporting development and approval of ADCs using the approved ADCs as specific examples to illustrate the customized approach to clinical pharmacology assessments in their clinical development.

scholarly journals Binding and functional profiling of antibody mutants guides selection of optimal candidates as antibody drug conjugates

PLoS ONE ◽  
2019 ◽  
Vol 14 (12) ◽  
pp. e0226593 ◽  
Author(s):  
John C. Zwaagstra ◽  
Traian Sulea ◽  
Jason Baardsnes ◽  
Stevo Radinovic ◽  
Yuneivy Cepero-Donates ◽  
...  
Keyword(s):  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Functional Profiling ◽  
Selection Of ◽  
Antibody Drug

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.

Sign in / Sign up

Export Citation Format

Share Document