Clinical Trial to Evaluate Antitumor Activity of Epidermal Growth Factor in Breast Cancer

May 1, 1996

ImClone Systems has initiated an additional phase Ib/IIa clinical trial of C225, the company's epidermal growth factor (EGF)-receptor antagonist. The dose-escalation study will evaluate C225 in conjunction with the chemotherapeutic agent paclitaxel

ImClone Systems has initiated an additional phase Ib/IIa clinicaltrial of C225, the company's epidermal growth factor (EGF)-receptorantagonist. The dose-escalation study will evaluate C225 in conjunctionwith the chemotherapeutic agent paclitaxel (Taxol) in patientssuffering from EGF receptor-positive breast carcinoma. C225 isdesigned to block the EGF receptor, which is overexpressed inseveral varieties of cancer. In combination with chemotherapyor radiation, C225 eliminates cancerous cells through a mechanismthat is believed to involve the induction of apoptosis, the naturalprocess of cell death.

The multisite trial will be conducted at Memorial Hospital, thepatient care arm of Memorial Sloan-Kettering Cancer Center, underthe direction of Larry Norton, MD, and at the Yale UniversitySchool of Medicine, Department of Medicine under the directionof Barbara Burtness, MD. Patients will receive C225 by weeklyintravenous administration in a multiple-injection dose-escalationstudy in combination with paclitaxel.

ImClone recently announced the initiation of a phase Ib/IIa clinicaltrial to evaluate C225 in conjunction with doxorubicin in patientssuffering from advanced prostate carcinoma. In addition, multiplephase Ib/IIa studies of C225 are currently being conducted inpatients with advanced head and neck and lung carcinomas. Patientsin these studies are being treated with C225 in combination withcisplatin (Platinol).

"The breast cancer study marks the third of our phase Ib/IIaclinical trials of C225 targeting specific tumors in combinationwith chemotherapeutic agents," said Harlan W. Waksal, MD,Executive Vice President and Chief Operating Officer of ImCloneSystems, "The results of these studies will provide valuablesafety and pharmacokinetic data regarding C225. Moreover, theywill further demonstrate the potential marketing breadth of thisproduct in various cancer indications."

Pronounced Activity Against Breast Cancer Cell Lines

Animal studies evaluating the use of C225 activity against humanbreast cancer cell lines showed pronounced antitumor activityresulting in the complete destruction of the human tumor cellsin the experimental model. These experiments also demonstratedlong-term tumor-free survival of the animals.

The EGF receptor is expressed in select normal human tissue andhas been shown to be overexpressed in the cells of approximatelyone-third of all cancers. Antibodies directed against the EGFreceptor may inhibit the uncontrolled cancer cell growth thathas been shown to be associated with this receptor's activity.Potential indications for C225 include head and neck, lung, breast,prostate, and ovarian cancers.