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

Invest New Drugs. 2015 Apr;33(2):380-8. doi: 10.1007/s10637-014-0196-0. Epub 2014 Dec 12.

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).

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / pharmacology*
  • Antineoplastic Agents
  • Asians
  • 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

Substances

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

Associated data

  • ClinicalTrials.gov/NCT01018784