Exelixis, Inc. announced that the phase 3 registration trial of XL184 as a potential treatment for medullary thyroid cancer (MTC) has been initiated. XL184 is a small molecule anticancer compound targeting the MET, RET, and VEGFR2 receptor tyrosine kinases.
Recently, Exelixis and the US Food and Drug Administration (FDA) reached agreement on the phase 3 registration trial via the Special Protocol Assessment process. Exelixis has also discussed the trial design with European regulatory agencies.
"We are thrilled that the pivotal trial for XL184 is now open for enrolment, and we look forward to rapid accrual of patients with MTC. We are hopeful that the results of this phase 3 trial will further substantiate the impressive data presented recently at ASCO and support registration of XL184 for the MTC indication, for which no standard of care is currently available," said Michael M. Morrissey, PhD, president of research and development at Exelixis. "The initiation of our first phase 3 trial for a compound wholly developed by Exelixis is a significant milestone for us and demonstrates the growth and integration of our R&D organization."
The phase 3 trial is 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 up to 100 sites in up to 20 countries will participate in this study.
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.
XL184 inhibits MET, RET, and VEGFR2, which are key drivers of tumour growth, metastasis, survival, and angiogenesis. In pharmacodynamic studies in mice, oral administration of XL184 resulted in balanced and durable inhibition of these targets. The compound has also shown activity against common mutant forms of RET and MET. XL184 has exhibited dose-dependent tumour growth inhibition and tumour regression in a variety of tumour models, including breast cancer, colon cancer, MTC, non-small cell lung cancer, and glioblastoma.
Exelixis, Inc. is a development-stage biotechnology company dedicated to the discovery and development of novel small molecule therapeutics for the treatment of cancer and other serious diseases.