Phase I study of amatuximab, a novel monoclonal antibody to mesothelin, in Japanese patients with advanced solid tumors
Summary Amatuximab is a chimeric monoclonal antibody that targets mesothelin, which is expressed in virtually all mesotheliomas and pancreatic adenocarcinomas. The objective of this study was to determine the dose-limiting toxicity and the maximum tolerated dose. Patients with mesothelioma, pancreat...
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Published in | Investigational new drugs Vol. 33; no. 2; pp. 380 - 388 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Boston
Springer US
01.04.2015
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Summary
Amatuximab is a chimeric monoclonal antibody that targets mesothelin, which is expressed in virtually all mesotheliomas and pancreatic adenocarcinomas. The objective of this study was to determine the dose-limiting toxicity and the maximum tolerated dose. Patients with mesothelioma, pancreatic adenocarcinoma or other mesothelin-positive solid tumors were eligible for this study. Amatuximab was administered weekly as an intravenous infusion in 4-week cycles at progressively increasing doses ranging from 50 to 200 mg/m
2
. Seventeen patients received amatuximab. Two dose-limiting toxicities were observed: one at 50 mg/m
2
and one at 200 mg/m
2
; the maximum tolerated dose of this study was determined to be 200 mg/m
2
. Of the 17 patients, 13 patients (76.5 %) experienced treatment-related adverse events. The most common adverse events were grade 1 fatigue (29.4 %) and pyrexia (23.5 %). The maximum serum concentration and area under the concentration curve values increased in an almost dose-proportional manner. Three patients had stable disease. Amatuximab was generally well tolerated at doses up to 200 mg/m
2
. The pharmacokinetic profile of amatuximab in the Japanese population was similar to that seen in the United States population (Clinical Trials.gov Identifier: NCT01018784). |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0167-6997 1573-0646 |
DOI: | 10.1007/s10637-014-0196-0 |