Exelixis reports data from cabozantinib phase 3 trial on MTC

Exelixis, Inc. (NASDAQ:EXEL) today reported data from the phase 3 pivotal trial of cabozantinib in patients with progressive, unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). The trial, known as EXAM, met its primary endpoint of improving progression-free survival (PFS), with patients in the cabozantinib arm achieving a median PFS of 11.2 months compared with 4.0 months for patients in the placebo arm. Overall response rate (ORR), a secondary endpoint, was 28% in the cabozantinib arm and 0% in the placebo arm. Estimated PFS at one year was 47.3% with cabozantinib vs. only 7.2% with placebo. Data for overall survival (OS), another secondary endpoint, are not yet mature. Patients on the cabozantinib arm of the trial received a dose of 140 mg (free base equivalent). Adverse events were generally manageable allowing for treatment with cabozantinib for prolonged periods of time. Exelixis recently submitted a New Drug Application (NDA) for cabozantinib in MTC to the U.S. Food and Drug Administration (FDA)

Dr. Patrick Schöffski, professor at the Department of General Medical Oncology at the University Hospitals of Leuven, Catholic University Leuven, Belgium, presented the data (Abstract #5508) today in an oral session at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois. The slides from the presentation are available at http://www.exelixis.com/resources/events/asco-2012.

"As the first phase 3 trial to enroll patients with independently confirmed radiographic progressing medullary thyroid cancer, EXAM represents an important milestone for this orphan disease in which there have been very few rigorous prospective clinical trials," said Dr. Schöffski. "The data presented today are highly compelling and demonstrate that cabozantinib can provide a significant benefit to patients with advanced MTC. Taken as a whole, the results clearly show that cabozantinib is an important advance in the treatment of MTC and has the potential to improve the care and outcomes for MTC patients."

Efficacy Results

All 330 patients were included in the efficacy analysis. Cabozantinib met the primary endpoint of the trial, with a median PFS of 11.2 months vs. 4.0 months for placebo [HR 0.28, p<0.0001] based on the independent radiology committee (IRC) evaluation. The Kaplan Meier estimate for the proportion of patients alive and progression-free at 1 year was 47.3% in the cabozantinib arm and 7.2% in the placebo arm. Other sensitivity analyses (investigator assessment, uniform date, and per protocol assessment) were consistent with the primary analysis. Cabozantinib's benefit on PFS was seen across a number of pre-specified subgroups including RET mutational status or prior tyrosine kinase inhibitor (TKI) therapy. With respect to secondary endpoints, the ORR, per RECIST evaluated by the IRC, was 28% in the cabozantinib arm and 0% in the placebo group. Median duration of response was 14.6 months. At the time of the June 2011 data cut-off, 44% of the events required for the OS analysis had occurred, making data on overall survival immature. At the time of the interim analysis, no difference in OS was observed between treatment arms. A final OS analysis will be conducted after 217 events have occurred.

"As seen in the initial topline results, and again today at the ASCO Annual Meeting, cabozantinib delivered a nearly three-fold increase in median PFS in the EXAM trial," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "The trial was conducted under a Special Protocol Assessment with the FDA, with progression-free survival as the primary endpoint, and we completed the submission of our NDA for MTC at the end of May. Beyond MTC, we are also excited about the encouraging interim cabozantinib data that have been generated in a variety of other tumor indications, including hepatocellular carcinoma, renal cell carcinoma and castration-resistant prostate cancer, which are the subjects of oral presentations at this year's ASCO Annual Meeting. In particular, the prostate cancer data formed the basis for advancing cabozantinib into two recently initiated phase 3 pivotal trials, COMET-1 and COMET-2."    

Source: Exelixis, Inc.

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