Phase I clinical evaluation of a neutralizing monoclonal antibody against epidermal growth factor receptor

Ior egf/r3, a neutralizing monoclonal antibody (mAb) against Epidermal Grow th Factor Receptor (EGFR) was generated at the Cuban Institute of Oncology. Immunoscintigraphic studies in 148 patients with this 99-m Technetium (Tc- 99) labeled mAb, showed a high sensitivity and specificity for in vivo dete ction of epithelial tumors. To study safety, pharmacokinetic and immunogeni city of ior egf/r3 at high doses, a phase I clinical trial was conducted. N ineteen patients with advanced epithelial tumors received 4 mAb intravenous infusions at 6 dose levels: from 50 to 500 mg. Previously, immunoscintigra phic images using the same mAb labeled with Tc-99 were acquired Blood sampl es 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 obser ved. In 13 patients, selective accumulation of Tc-99-labeled mAb was observ ed at the site of the primary tumor or the metastasis. Pharmacokinetic anal ysis revealed that elimination half-life and the area under the time-concen tration curve increased linearly with dose. HAMA response was detected in 1 7 patients. After 6 months of mAb therapy 4 patients had stable disease. On e patient had a tumor partial remission after 3 cycles of ior egf/r3.