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Cabozantinib Demonstrates Improved Progression-free Survival in Phase 3 Trial
Exelixis will consult with the FDA to determine whether the trial conduct should be changed as a result of these data in conjunction with the SPA. The company is requesting permission to begin a rolling submission of the New Drug Application (NDA) for cabozantinib in this indication to the U.S. Food and Drug Administration (FDA). It is anticipated that the filing will be completed in the first half of 2012.
“The prospect of a new highly effective therapy for MTC gives patients and physicians a reason for great optimism,” said Steven I. Sherman, M.D., Chair and Naguib Samaan Distinguished Professor in Endocrinology and Medical Director, Endocrine Multidisciplinary Center at MD Anderson Cancer Center, who was also an investigator in the study. “Personally, as a clinician who treats many patients with advanced MTC, it is particularly gratifying to see Exelixis’ commitment to the thorough evaluation of cabozantinib in this indication in a large phase 3 study, and the resultant positive outcome of the trial. This represents important progress in the treatment of MTC, an indication that has long been underserved and still has a significant unmet medical need. I believe that cabozantinib has great potential to improve the care and outcomes of MTC patients.”
EXAM Trial Design
EXAM is an international, randomized, placebo-controlled, double-blinded study of cabozantinib in patients with progressive, unresectable, locally advanced, or metastatic MTC. Patients were randomized in a 2:1 ratio to receive cabozantinib or placebo administered at a daily dose of 175 mg. The study did not allow for cross-over from the placebo arm to cabozantinib. With an enrollment target of 315 patients and a planned event-driven analysis, the trial provides 90% power to detect a 75% increase in progression-free survival, the primary endpoint of the study. Additionally the study is designed to assess overall survival at a later time point once those events have been achieved, and is powered to detect a 50% improvement in survival compared with placebo. Exelixis is conducting this trial under a SPA from the FDA, which allows for full approval on the basis of PFS if the data are supportive. EXAM completed enrollment in the first quarter of 2011. Cabozantinib Development Program
As previously announced, Exelixis is pursuing a SPA with the U.S. FDA for the first of three planned pivotal trials of cabozantinib in patients with prostate cancer. This trial, XL184-306, is expected to begin by the end of 2011. Exelixis is also working to finalize the design of the XL184-307 and XL184-308 pivotal trials in prostate cancer, which will have endpoints of overall survival and bone metastasis-free survival, respectively. Both trials are expected to begin in 2012. Enrollment is also ongoing in the non-randomized extension (NRE) cohorts in metastatic castration-resistant prostate cancer and ovarian cancer of the company’s randomized discontinuation trial (RDT). The RDT and the NRE cohorts are designed to identify additional indications for late-stage clinical evaluation. About Cabozantinib
Cabozantinib is a potent inhibitor of MET, RET and VEGFR2 that inhibits tumor growth, metastasis and angiogenesis in preclinical models. MET is up-regulated in many tumor types, and promotes tumor cell survival, invasion and metastasis. Further up-regulation of MET occurs under hypoxic conditions, which are often exacerbated by VEGF-pathway inhibitors, promoting increased tumor cell invasion and metastases. Activation of RET is a frequent occurrence in both medullary and papillary thyroid cancers. The therapeutic role of cabozantinib is currently being investigated across multiple tumor types.