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
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.