Phase I study of amatuximab, a novel monoclonal antibody to mesothelin, in Japanese patients with advanced solid tumors.

Abstract

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).

• Authors: Yasuhito Fujisaka, Takayasu Kurata, Kaoru Tanaka, Toshihiro Kudo, Kunio Okamoto, Junji Tsurutani, Hiroyasu Kaneda, Isamu Okamoto, Masayuki Namiki, Chifumi Kitamura, Kazuhiko Nakagawa
• Journal: Investigational new drugs (Invest New Drugs) Vol. 33 Issue 2 Pg. 380-8 (Apr 2015) ISSN: 1573-0646 [Electronic] United States
• PMID: 25502863 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• GPI-Linked Proteins
• amatuximab
• Mesothelin

Topics

• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects, pharmacokinetics, pharmacology)
• Antineoplastic Agents
• Asian People
• Dose-Response Relationship, Drug
• Female
• GPI-Linked Proteins (biosynthesis)
• Half-Life
• Humans
• Japan
• Male
• Maximum Tolerated Dose
• Mesothelin
• Metabolic Clearance Rate
• Middle Aged
• Neoplasms (drug therapy)