Population pharmacokinetics and exposure-response relationship of amatuximab, an anti-mesothelin monoclonal antibody, in patients with malignant pleural mesothelioma and its application in dose selection.

Cancer Chemotherapy and Pharmacology
Anubha GuptaBruce A Wallin

Abstract

To characterize amatuximab pharmacokinetics (PK) and the relationship of amatuximab exposure with response in patients with unresectable malignant pleural mesothelioma (MPM) receiving amatuximab with pemetrexed and cisplatin. A nonlinear mixed effects PK model was built using data from all of the amatuximab studies conducted to date. Patients received amatuximab alone or in combination with chemotherapy. The influence of demographic, laboratory and disease characteristics on PK parameters was assessed. Exposure-response analyses explored relationships between amatuximab exposure and overall survival (OS), progression-free survival (PFS) and safety. Alternative amatuximab dosing regimens were explored with simulations using population PK and parametric survival models. Amatuximab PK was best described by a two-compartment model with parallel linear and nonlinear elimination pathways. Body weight and an antidrug antibodies reaction with the titer >64 affected volume of distribution and clearance, respectively. Exposure-response analyses demonstrated that the amatuximab exposure (C min) showed a significant effect on OS (log-rank test, P = 0.0202). For patients with amatuximab C min above the median (38.2 μg/mL), the median OS was...Continue Reading

References

Feb 1, 1992·International Journal of Cancer. Journal International Du Cancer·K ChangM C Willingham
Jul 15, 1993·Cancer·V De Pangher ManziniC Bianchi
Jan 5, 2002·Journal of Pharmacokinetics and Pharmacodynamics·S L Beal
Mar 18, 2003·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Nelson G Ordóñez
Jul 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nicholas J VogelzangPaolo Paoletti
Aug 6, 2005·Applied Immunohistochemistry & Molecular Morphology : AIMM·Raffit HassanMark C Willingham
Jan 19, 2006·American Journal of Clinical Pathology·Raffit HassanDaniel Brackett
Jun 16, 2007·Clinical Pharmacology and Therapeutics·M O Karlsson, R M Savic
May 20, 2009·The AAPS Journal·Martin Bergstrand, Mats O Karlsson
Sep 12, 2009·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Raffit HassanIra Pastan
Jan 9, 2010·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Diane R Mould, Bruce Green
Sep 8, 2010·Clinical Pharmacokinetics·Nathanael L Dirks, Bernd Meibohm
Nov 3, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Raffit HassanDaniel Laheru
Feb 9, 2011·The AAPS Journal·Martin BergstrandMats O Karlsson
Feb 22, 2012·Molecular Cancer Therapeutics·Ronan J KellyRaffit Hassan
Sep 19, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Raffit HassanBruce A Wallin

❮ Previous
Next ❯

Citations

Aug 30, 2019·Biomarker Research·Jiang Lv, Peng Li
Nov 20, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Raffit HassanIra Pastan
Jun 11, 2020·International Journal of Molecular Sciences·Christopher MontemagnoGilles Pagès
Dec 11, 2019·Antibodies·Veena A Thomas, Joseph P Balthasar
May 29, 2018·Clinical Pharmacokinetics·David TernantGilles Paintaud
Aug 28, 2019·Clinical Pharmacokinetics·Antoine PetitcollinDavid Ternant
Nov 13, 2020·Expert Opinion on Biological Therapy·Astero KlampatsaSteven M Albelda

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Raffit HassanBruce A Wallin
European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
Jaine K BlayneyDean A Fennell
© 2022 Meta ULC. All rights reserved