Monoclonal Antibody Combined With Chemo or Radiation Studied in Advanced Head and Neck Cancer

The findings of two clinical studies of C225, a monoclonal antibody (epidermal growth factor receptor inhibitor) being developed by ImClone Systems (New York City), were presented at the 1999 annual meeting of the American Society of Clinical Oncology (ASCO). The studies demonstrated the effectiveness of C225 in eliciting a clinical response in patients with advanced head and neck cancer when used in combination with standard radiotherapy and chemotherapeutic agents.

John Mendelsohn, MD, president of M. D. Anderson Cancer Center, presented data from a phase Ib/IIa study of nine treated and evaluable patients with refractory advanced squamous cell head and neck carcinoma who were treated with the combination of C225 and cisplatin (Platinol). The results demonstrated a response rate of 66%, with one complete response and five partial responses. All of the patients who responded to the combination had been unresponsive to previous treatment regimens, including standard chemotherapy, radiotherapy, and experimental treatments. In particular, three of the six responders (including the complete responder) had not responded to prior cisplatin treatment.

“The cisplatin study is a significant step in the development of C225 because of the impressive response rate and because we observed that patients who have progressed after cisplatin therapy respond when it is then combined with C225,” said Dr. Mendelsohn. “With further clinical evaluation, C225 with cisplatin may prove to be an effective initial therapy and an effective treatment for patients who have failed previous chemotherapy. These patients currently have few treatment options.”

C225 Also Effective With Radiotherapy

Also during ASCO, Mark Ezekiel, MD, Department of Radiation Oncology, University of Alabama Medical Center, Birmingham, presented the findings of a phase Ib/IIa dose-escalation study of a combination of C225 and radiation therapy in 15 treated patients with stage III or IV locally advanced head and neck cancer. The combination of C225 and radiotherapy produced responses in all 15 evaluable patients, including 13 complete responses and 2 partial responses. In addition, the median duration of response was greater than 12 months. These results compared favorably with published response rates of 30% to 40% using radiation therapy alone.

Future Trials Planned

“The data presented at the ASCO conference is extremely encouraging, not only because it adds to the positive clinical data we have accumulated on C225 in this cancer area, but also because it may prove to benefit patients who have failed prior chemotherapy treatment,” said Samuel D. Waksal, president and chief executive office of ImClone Systems. “We intend to initiate a phase II study in this refractory patient population in the near term.”

ImClone has recently initiated two phase III clinical trials evaluating C225 in combination with chemotherapy and radiotherapy in patients with advanced squamous cell head and neck carcinoma.