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
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."
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.