Exelixis Reaches Agreement with FDA on Special Protocol Assessment for XL184 Phase 3 Trial

Tue, 06/17/2008 - 6:24am
Exelixis, Inc. announced recently that the company and the FDA have reached agreement on the phase 3 registration trial of XL184, a small molecule anticancer compound targeting MET, RET, and VEGFR2, via the Special Protocol Assessment process. Exelixis has also discussed the trial design with European regulatory agencies. Exelixis is planning to initiate the phase 3 trial of XL184 as a potential treatment for medullary thyroid cancer (MTC) this summer.The phase 3 trial has been designed in collaboration with internationally renowned experts in the field of thyroid malignancies, including Dr. Steven Sherman from the MD Anderson Cancer Center in Houston, Texas, Drs. Douglas Ball and Barry Nelkin from Johns Hopkins University in Baltimore, Maryland, and Dr. Martin Schlumberger from the Institut Gustave Roussy in Paris, France. This will be a randomized, placebo-controlled, double-blinded study of XL184 as single-agent therapy in 315 patients with unresectable, locally advanced, or metastatic MTC. Patients will be randomized in a 2:1 ratio to receive XL184 or placebo administered as a daily oral dose. The primary endpoint will be duration of progression-free survival. In a planned event-driven analysis, the study size provides 90% power to detect a 75% increase in progression-free survival in patients with documented progressive disease prior to study entry. Secondary endpoints will include overall survival, objective tumor response rate, and changes in serum biomarkers (carcinoembryonic antigen and calcitonin). Additional secondary endpoints will be assessment of the potential relationship between germline and/or tumor DNA sequence alterations and the efficacy of XL184, as well as assessment of pharmacodynamics and pharmacokinetics of XL184. It is expected that approximately 100 sites in 20 countries will participate in this study."We are very encouraged by the level of clinical activity in the ongoing XL184 phase 1 study showing a high response rate and durable disease control in medullary thyroid cancer patients, and believe that the FDA-approved phase 3 study design will allow us to rigorously evaluate the clinical benefit of XL184 in this population for which no standard of care is available," said Gisela Schwab, MD, executive vice president and chief medical officer at Exelixis.The planned initiation of this phase 3 trial is based on encouraging data that were presented earlier this month at the 2008 annual meeting of the American Society of Clinical Oncology (ASCO). Safety and clinical activity data were presented from an ongoing phase 1 trial of XL184 in 69 patients with various solid tumors, including 17 response-evaluable patients with MTC. These data showed a disease control rate (percentage of patients with partial responses or prolonged stable disease >3 months) of 100% in the evaluable MTC patients, with 53% of those patients (9 of 17) experiencing partial responses. The median duration of partial responses and stable disease for patients with MTC has not been reached (range 1+ to 22+ months). Most of the MTC patients in the trial had previously failed other treatments, including tyrosine kinase inhibitors with anti-RET activity (e.g., vandetanib, sorafenib, or motesanib), chemotherapeutic agents, immunotherapy, radioactive iodine, and radiotherapy.Several additional studies with XL184 have recently been initiated to complement the planned pivotal trial in patients with MTC as part of Exelixis' strategy to rapidly advance compounds into areas of high unmet medical need while potentially expanding into broader commercial markets by demonstrating activity in major tumor types. A phase 1/2 trial of XL184 as a single agent and in combination with erlotinib was recently initiated in patients with non- small cell lung cancer. In addition, a phase 2 study of XL184 in patients with glioblastoma multiforme is ongoing./t2>

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