Phase 1 study of anti-epidermal growth factor receptor monoclonal antibody in patients with solid tumors

MAbs. 2011 Jan-Feb;3(1):67-75. doi: 10.4161/mabs.3.1.14021. Epub 2011 Jan 1.

Abstract

In the present study, we conducted a Phase 1 study of a recombinant anti-EGFR monoclonal antibody (CMAB009) that has the same amino acid sequence as cetuximab. The purpose of this study was to evaluate the safety, pharmacokinetics, and potential benefit of CMAB009 in Chinese patients with advanced chemotherapy-resistant epithelial malignancies. In this study, 18 patients were treated with two successive treatment schedules comprising a single-dose escalation phase followed by a weekly, multiple-dose extension phase. No dose-limiting toxicity was reported during the evaluation period. CMAB009-associated toxicity was minimal, and the most commonly reported adverse events were fever, asthenia, transaminase elevation, nausea, and skin toxicities. CMAB009 exhibited a non-linear PK profile over the dose range of 100 to 400 mg/m2. In the single-dose phase, CMAB009 reached peak serum concentrations at the end of the infusion and then declined slowly with a Tl/2 of 77.15 ±13.96 h, 79.79 ±6.91 h, and 86.25 ±9.93 h after infusion of 100, 250, and 400 mg/m ( 2) based on a two compartmental model analysis. Mean Cmax increased roughly dose-proportional while AUC0-∞ showed a greater than dose-proportionate increase from 100 to 400 mg/m ( 2) . After multiple infusions, serum concentrations dropped slowly and the Tl/2 was 102.25 ± 33.54 h and 118.91 ± 29.12 h based on a two compartmental model analysis. No neutralizing anti-antibody antibodies were detectable. Two patients achieved partial remissions. The study results suggest that CMAB009 shows acceptable tolerance and primary efficacy and should be studied as a treatment in patients with advanced chemotherapy-resistant epithelial malignancies.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Area Under Curve
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Dose-Response Relationship, Drug
  • ErbB Receptors / immunology*
  • Exanthema / chemically induced
  • Female
  • Fever / chemically induced
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Nausea / chemically induced
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Treatment Outcome
  • Vomiting / chemically induced

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • CMAB009
  • ErbB Receptors