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Tarceva (erlotinib HCI) Shows Encouraging Safety Profile and Activity in Phase I Clinical Study in Patients with Malignant Glioma -- Genentech and OSI Pharmaceuticals Moving Forward to Initiate Phase II Study --
May 31, 2003 -- Genentech and OSI Pharmaceuticals, Inc. announced encouraging results from a Phase I clinical study of TarcevaT (erlotinib HCl) in patients with malignant glioma (brain cancer). Tarceva is designed to inhibit the tyrosine kinase activity of the HER1/EGFR signaling pathway inside the cell, which may block tumor cell growth.
"We are very encouraged by the safety profile and the response rates seen in this Phase I study in glioma, a disease in which HER1/EGFR may play a special role," stated Susan D. Hellmann, M.D., MPH, Genentech´s executive vice president, Development and Product Operations, and chief medical officer. "Glioma is the most malignant form of brain cancer, and there is a tremendous unmet medical need because current therapies have shown minimal impact to alter the course of the disease."
Based on an encouraging safety profile and clinical activity observed in this Phase I study (Abstract #394), Genentech and OSI have made a decision to move forward with a Phase II trial of Tarceva in glioma in the U.S. This Phase II clinical trial will be conducted in collaboration with the Accelerate Brain Cancer Cure (ABC2) Clinical Network of leading neuro-oncology centers. ABC2 is a non-profit foundation that funds novel translational science aimed at the discovery of a cure for brain cancer.
Results of Phase I Glioma Clinical Trial
The study, led by Michael Prados, M.D., of the University of California, San Francisco, evaluated the safety and pharmacokinetics (PK) of Tarceva in patients with malignant glioma. Patients with stable or progressive malignant glioma were treated with Tarceva, starting at 100 mg/day and received an additional 50 mg/day until a dose-limiting toxicity occurred. The 26 patients were stratified based on the use of enzyme inducing antiepileptic drugs (EIAEDs), which are used to prevent seizures. In addition to receiving Tarceva, some patients also received temozolomide, a type of chemotherapy.
Sixteen percent of the evaluable patients (8/49) achieved a response after treatment with Tarceva. Dr. Prados reported that the number of objective responses observed in this study was encouraging. Dose-limiting toxicities occurred in six patients, primarily due to skin rash. To date, the maximum tolerated dose has not been reached.
"In addition to encouraging indications of clinical activity, the dose escalation component of this study has allowed us to use Tarceva at doses where essentially all patients develop rash, which in other studies appears to correlate with improved survival," said Nicole Onetto, M.D., executive vice president and chief medical officer, OSI Pharmaceuticals.