Phase I clinical evaluation of a neutralizing monoclonal antibody against Epidermal Growth Factor Receptor

Abstract:

Ior egf/r3 a neutralizing monoclonal antibody (mAb) against Epidermal Growth Factor Receptor (EGFR) was generated at the Cuban Institute of Oncology. Immunoscintigraphic studies in 148 patients with this 99-m Technetium (⁹⁹Tc) labeled mAb showed a high sensitivity and specificity for in vivo detection of epithelial tumors. To study safety pharmacokinetic and immunogenicity of ior egf/r3 at high doses a phase I clinical trial was conducted. Nineteen patients with advanced epithelial tumors received 4 mAb intravenous infusions at 6 dose levels: from 50 to 500 mg. Previously immunoscintigraphic images using the same mAb labeled with ⁹⁹Tc were acquired. Blood samples were collected for pharmacokinetic analysis and HAMA response. After mAb therapy objective response was classified according to WHO criteria. Ior egf/r3 was well tolerated in spite of the high-administered doses. Only a severe adverse reaction consisting of hypotension and lethargy was observed. In 13 patients selective accumulation of ⁹⁹Tc-labeled mAb was observed at the site of the primary tumor or the metastasis. Pharmacokinetic analysis revealed that elimination half-life and the area under the time-concentration curve increased linearly with dose. HAMA response was detected in 17 patients. After 6 months of mAb therapy 4 patients had stable disease. One patient had a tumor partial remission after 3 cycles of ior egf/r3.

Año de publicación:

2001

Keywords:

• Epidermal growth factor receptor
• Monoclonal antibody
• immunotherapy
• Tyrosine kinase inhibitors
• Phase I clinical trial

Fuente:

scopus