Katja Heinig1, Kazuhiro Miya2, Tomonori Kamei2, Elena Guerini1, Daniela Fraier1, Li Yu3, Surendra Bansal3, Peter N Morcos3. 1. Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland. 2. Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara Kamakura Kanagawa, 247-8530 Japan. 3. Roche Pharmaceutical Research & Early Development, Roche Innovation Center New York, F. Hoffmann-La Roche Ltd, 430 East 29th Street, New York, NY 10016, USA.
Abstract
BACKGROUND: Alectinib is a novel anaplastic lymphoma kinase (ALK) inhibitor for treatment of patients with ALK-positive non-small-cell lung cancer who have progressed on or are intolerant to crizotinib. To support clinical development, concentrations of alectinib and metabolite M4 were determined in plasma from patients and healthy subjects. METHODS: LC-MS/MS methods were developed and validated in two different laboratories: Chugai used separate assays for alectinib and M4 in a pivotal Phase I/II study while Roche established a simultaneous assay for both analytes for another pivotal study and all other studies. CONCLUSION: Cross-validation assessment revealed a bias between the two bioanalytical laboratories, which was confirmed with the clinical PK data between both pivotal studies using the different bioanalytical methods.
BACKGROUND:Alectinib is a novel anaplastic lymphoma kinase (ALK) inhibitor for treatment of patients with ALK-positive non-small-cell lung cancer who have progressed on or are intolerant to crizotinib. To support clinical development, concentrations of alectinib and metabolite M4 were determined in plasma from patients and healthy subjects. METHODS: LC-MS/MS methods were developed and validated in two different laboratories: Chugai used separate assays for alectinib and M4 in a pivotal Phase I/II study while Roche established a simultaneous assay for both analytes for another pivotal study and all other studies. CONCLUSION: Cross-validation assessment revealed a bias between the two bioanalytical laboratories, which was confirmed with the clinical PK data between both pivotal studies using the different bioanalytical methods.
Authors: Peter N Morcos; Eveline Nueesch; Felix Jaminion; Elena Guerini; Joy C Hsu; Walter Bordogna; Bogdana Balas; Francois Mercier Journal: Cancer Chemother Pharmacol Date: 2018-05-10 Impact factor: 3.333