- Study Met Primary Endpoint of Significantly Improving
Progression-Free Survival -
- Cabozantinib Reduced the Risk of Disease Progression or Death by
42%; Hazard Ratio = 0.58, (p < 0.0001) Compared to Everolimus -
- Overall Survival Interim Analysis Showed a Trend Favoring
Cabozantinib; Hazard Ratio = 0.67, (p = 0.005) Compared to Everolimus -
- Exelixis to Complete U.S. and EU Regulatory Filings in Early
- Conference Call at 8:30 AM EDT / 5:30 AM PDT Today -
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Jul. 20, 2015--
Exelixis, Inc. (NASDAQ:EXEL) today announced positive top-line results
from the primary analysis of METEOR, the phase 3 pivotal trial comparing
cabozantinib to everolimus in 658 patients with metastatic renal cell
carcinoma (RCC) who have experienced disease progression following
treatment with a VEGF receptor tyrosine kinase inhibitor (TKI).
The trial met its primary endpoint of demonstrating a statistically
significant increase in progression-free survival (PFS) in the first 375
randomized patients as determined by an independent radiology committee
(IRC). Cabozantinib reduced the risk of disease progression or death by
42 percent compared to the everolimus arm (hazard ratio [HR]=0.58, 95
percent CI 0.45-0.75, p<0.0001).
Data pertaining to overall survival (OS) in the entire study population
of 658 patients, a secondary endpoint of the trial, were immature at the
data cutoff. A prespecified interim analysis, triggered by the primary
analysis for PFS, showed a trend in OS favoring cabozantinib (HR = 0.67,
unadjusted 95 percent CI 0.51 - 0.89; p=0.005). At the time of the
interim analysis, the pre-specified p-value of 0.0019 to achieve
statistical significance was not reached. The trial will continue to the
final analysis of OS anticipated in 2016.
METEOR’s primary analysis included a review of serious adverse event
(SAE) data. Based on this analysis, the frequency of SAEs of any Grade
regardless of causality was approximately balanced between study arms.
The rate of treatment discontinuation due to adverse events was low
(10%) in both study arms.
Detailed results of the trial will be submitted for presentation at an
upcoming medical conference.
In April 2015, cabozantinib received Fast Track designation by the U.S.
Food and Drug Administration (FDA) for the potential treatment of
advanced RCC patients who have received one prior therapy. Based on the
outcome of METEOR, Exelixis plans to complete regulatory filings in the
United States and European Union in early 2016.
“We are eager to offer new treatment options for patients with
metastatic RCC, particularly in the second-line setting where the most
commonly utilized therapies have demonstrated a uniformly modest
progression-free survival benefit,” said Toni K. Choueiri, M.D.,
clinical director of the Lank Center for Genitourinary Oncology at
Dana-Farber Cancer Institute, and METEOR’s principal investigator. “The
magnitude of the improvement in PFS observed with cabozantinib compared
to everolimus in the METEOR trial is an exciting and important
development — it suggests an opportunity to improve care and outcomes
for patients with metastatic RCC.”
“The positive top-line results from METEOR represent strong progress for
the kidney cancer community and for Exelixis, bringing us one step
closer to our shared goal of delivering a new and meaningfully
differentiated therapeutic option for the many metastatic RCC patients
in need,” said Michael M. Morrissey, Ph.D., the company’s president and
chief executive officer. “With these data now in hand, Exelixis’ highest
corporate priority becomes the submission of U.S. and EU regulatory
filings, which we intend to complete in early 2016.”
Dr. Morrissey continued, “Delivering these top-line results for METEOR
is one of multiple clinical development and regulatory milestones that
we have planned for this year. These milestones collectively have the
potential to significantly enhance the opportunities before us and bring
value to the multiple stakeholders we serve. We look forward to sharing
the detailed results of METEOR with the oncology community at an
upcoming medical conference, and we thank all of the patients, families,
investigators, and clinical staff who made the trial possible.”
Conference Call and Webcast
Exelixis' management will host a conference call to discuss the METEOR
results beginning at 8:30 a.m. EDT/ 5:30 a.m. PDT today, July 20, 2015.
To join the call, participants may dial 877-358-0169 (domestic) or
706-679-2029 (international) and provide the conference call passcode
90168151 to join by phone. To listen to a live webcast of the conference
call, visit the Event Calendar page under Investors & Media at www.exelixis.com.
An archived replay of the webcast will be available on the Event
Calendar page under Investors & Media at www.exelixis.com
for at least thirty days. An audio-only phone replay will be available
until 11:59 p.m. EDT on July 22, 2015. Access numbers for the phone
replay are: 855-859-2056 (domestic) and 404-537-3406 (international);
the passcode is 90168151.
About the METEOR Phase 3 Pivotal Trial
METEOR is an open-label, event-driven trial with the primary endpoint of
progression-free survival (PFS). The target enrollment for METEOR was
650 patients, and 658 patients were ultimately randomized. The trial was
conducted at approximately 200 sites in 26 countries, and enrollment was
weighted toward Western Europe, North America, and Australia. Patients
were randomized 1:1 to receive 60 mg of cabozantinib daily or 10 mg of
everolimus daily, and were stratified based on the number of prior VEGF
receptor TKI therapies received, and on commonly applied RCC risk
criteria developed by Motzer et al. No cross-over was allowed
between the study arms.
The trial protocol specified that the primary analysis of PFS would be
conducted among the first 375 patients randomized. This design was
employed to ensure sufficient follow up and a PFS profile that would not
be primarily weighted toward early events. Such disproportionate
weighting of events was a potential risk if the entire study population
required for the secondary endpoint analysis of OS had also served as
the population for the primary analysis of PFS. The analysis of PFS was
event-driven, and was designed to observe 259 events, providing 90%
power to detect a HR of 0.67 (assuming a median PFS of 5 months for the
everolimus arm and 7.5 months for the cabozantinib arm). Enrollment of
the first 375 patients was completed in June 2014 and the median
follow-up for these patients was 13.4 months at the time of the data cut
off for the primary analysis for PFS.
Secondary endpoints for METEOR include OS and objective response rate.
The secondary endpoint of OS assumes a median of 15 months for the
everolimus arm and 20 months for the cabozantinib arm. The study was
designed to observe 408 deaths in the entire intent-to-treat population
of 650 planned patients, providing 80% power to detect a HR of 0.75. An
interim analysis of OS at the 2-sided 0.0019 level per the Lan-DeMets
O’Brien-Fleming alpha-spending function was planned at the time of the
primary analysis for PFS, if the trial met the primary PFS endpoint.
About Metastatic Renal Cell Carcinoma
The American Cancer Society’s 2015 statistics cite kidney cancer as
among the top ten most commonly diagnosed forms of cancer among both men
and women in the United States.1 Clear cell renal cell
carcinoma is the most common type of kidney cancer in adults.2
If detected in its early stages, the five-year survival rate for RCC is
high; however, the five-year survival rate for patients with advanced or
late-stage metastatic RCC is under 10 percent, with no identified cure
for the disease.3
Treatments for metastatic RCC had historically been limited to cytokine
therapy (e.g., interleukin-2 and interferon) until the introduction of
targeted therapies into the RCC setting a decade ago. In the second and
later-line setting, which encompasses approximately 17,000 drug-eligible
patients in the U.S. and 37,000 globally,4 two therapies have
been approved for the treatment of patients who have received prior VEGF
receptor TKIs. However, despite the availability of several therapeutic
options, currently approved agents have shown little differentiation in
terms of efficacy and have demonstrated only modest PFS benefit in
patients refractory to sunitinib, a commonly-used first-line therapy.
The majority of clear cell RCC tumors exhibit down-regulation of von
Hippel-Lindau (VHL) protein function, either due to gene inactivation or
epigenetic silencing, resulting in a stabilization of the
hypoxia-inducible transcription factors (HIFs) and consequent
up-regulation of VEGF, MET, and AXL.5 The up-regulation of
VEGF may contribute to the angiogenic nature of clear cell RCC, and
expression of MET or AXL may be associated with tumor cell viability, a
more invasive tumor phenotype, and reduced overall survival. 6
Up-regulation of MET and AXL in clear cell RCC has also been shown to
occur in response to treatment with VEGF receptor TKIs in preclinical
models, indicating a potential role for MET and AXL in the development
of resistance to these therapies.7
Cabozantinib inhibits the activity of tyrosine kinases including MET,
VEGF receptors, AXL, and RET. These receptor tyrosine kinases are
involved in both normal cellular function and in pathologic processes
such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of
the tumor microenvironment.
COMETRIQ® (cabozantinib) is currently approved by the U.S.
Food and Drug Administration for the treatment of progressive,
metastatic medullary thyroid cancer (MTC).
The European Commission granted COMETRIQ conditional approval for the
treatment of adult patients with progressive, unresectable locally
advanced or metastatic MTC. Similar to another drug approved in this
setting, the approved indication states that for patients in whom
Rearranged during Transfection (RET) mutation status is not known or is
negative, a possible lower benefit should be taken into account before
individual treatment decisions.
Important Safety Information, including Boxed WARNINGS
WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE
Serious and sometimes fatal gastrointestinal perforations and
fistulas occur in COMETRIQ-treated patients.
Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated
COMETRIQ treatment results in an increase in thrombotic events, such
as heart attacks.
Wound complications have been reported with COMETRIQ.
COMETRIQ treatment results in an increase in hypertension.
Osteonecrosis of the jaw has been observed in COMETRIQ-treated
Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurs in patients
treated with COMETRIQ.
The kidneys can be adversely affected by COMETRIQ. Proteinuria and
nephrotic syndrome have been reported in patients receiving COMETRIQ.
Reversible Posterior Leukoencephalopathy Syndrome has been observed
Avoid administration of COMETRIQ with agents that are strong CYP3A4
inducers or inhibitors.
COMETRIQ is not recommended for use in patients with moderate or
severe hepatic impairment.
COMETRIQ can cause fetal harm when administered to a pregnant woman.
Adverse Reactions – The most commonly reported adverse drug reactions
(≥25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia
syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue,
oral pain, hair color changes, dysgeusia, hypertension, abdominal pain,
and constipation. The most common laboratory abnormalities (≥25%) are
increased AST, increased ALT, lymphopenia, increased alkaline
phosphatase, hypocalcemia, neutropenia, thrombocytopenia,
hypophosphatemia, and hyperbilirubinemia.
Please see full U.S. prescribing information, including Boxed WARNINGS,
Please refer to the full European Summary of Product Characteristics for
full European Union prescribing information, including contraindication,
special warnings and precautions for use at www.sobi.com
Exelixis, Inc. is a biopharmaceutical company committed to developing
small molecule therapies for the treatment of cancer. Exelixis is
focusing its development and commercialization efforts primarily on
COMETRIQ® (cabozantinib), its wholly-owned inhibitor of
multiple receptor tyrosine kinases. Another Exelixis-discovered
compound, cobimetinib, a selective inhibitor of MEK, is being evaluated
by Roche and Genentech (a member of the Roche Group) in a broad
development program under a collaboration with Exelixis. For more
information, please visit the company's web site at www.exelixis.com.
Forward-Looking Statement Disclaimer
The statements in this press release that Exelixis plans to complete
U.S. and EU regulatory filings in early 2016, that the trial will
continue to the final analysis of OS which is anticipated in early 2016,
that detailed results of the trial will be submitted for presentation at
an upcoming medical conference, that the results of the trial suggest an
opportunity to improve care and outcomes for patients with metastatic
RCC, regarding the potential that delivering upon top-line results for
METEOR and other planned clinical development and regulatory milestones
for this year will significantly enhance the opportunities before
Exelixis and bring value to the multiple stakeholders Exelixis serves,
are forward-looking statements that are subject to risk and uncertainty.
These forward-looking statements are based upon Exelixis’ current plans,
assumptions, beliefs, expectations, estimates and projections.
Forward-looking statements involve risks and uncertainties. Actual
results and the timing of events could differ materially from those
anticipated in the forward-looking statements as a result of these risks
and uncertainties, which include, without limitation: the clinical,
therapeutic and commercial value of cabozantinib; the availability of
data at the expected times; risks related to the potential failure of
cabozantinib to demonstrate safety and efficacy in clinical study;
Exelixis' ability to conduct clinical trials of cabozantinib sufficient
to achieve a positive completion; risks and uncertainties related to
regulatory review and approval processes and Exelixis' compliance with
applicable legal and regulatory requirements; the general sufficiency of
Exelixis' capital and other resources; the uncertain timing and level of
expenses associated with the development of cabozantinib; market
competition; changes in economic and business conditions; and other
factors discussed under the caption “Risk Factors” in Exelixis’
quarterly report on Form 10-Q filed with the Securities and Exchange
Commission (SEC) on April 30, 2015, and in Exelixis’ other filings with
the SEC. The forward-looking statements made in this press release speak
only as of the date of this press release. Exelixis expressly disclaims
any duty, obligation or undertaking to release publicly any updates or
revisions to any forward-looking statements contained herein to reflect
any change in Exelixis’ expectations with regard thereto or any change
in events, conditions or circumstances on which any such statements are
Exelixis, the Exelixis logo, and COMETRIQ are registered U.S.
1 Cancer Facts & Figures 2015. American Cancer Society.
2 Jonasch et al., BMJ (2014) vol. 349, g4797.
4 ACS Cancer Facts and Figures 2015; Heng et al., Ann
Oncol (2012) vol. 23 no. 6; internal data on file; Motzer et al., N Engl
J Med (2007) vol. 356 no. 2; NCIN (UK) report, April 2014, Available at http://www.ncin.org.uk/view?rid=2676.
5 Harschman and Choueiri, Cancer J. 2013 v19 316-323;
Rankin et al., PNAS, 2014.
6 Bommy-Reddi et al., PNAS, 2008; Gibney et al., Ann.
Oncol. 2013 v24 343-349; Koochekpour et al., Mol. Cell. Biol. 1999, v19
5902-5912; Rankin et al., PNAS, 2014.
7 Ciamporcero et al., MolCancerTher, 2014; Rankin et al.,
View source version on businesswire.com: http://www.businesswire.com/news/home/20150720005611/en/
Source: Exelixis, Inc.
Investor Relations and Corporate
For Exelixis, Inc.