Press Release
Press Release
Exelixis Announces Positive Overall Survival Results from METEOR, the Phase 3 Pivotal Trial of Cabozantinib in Advanced Renal Cell Carcinoma
– Cabozantinib significantly improved overall survival as compared with everolimus –
– First therapy to demonstrate improvement in overall survival, progression-free survival, and objective response rate in a large, pivotal phase 3 study in previously treated renal cell carcinoma patients –
–
“With these results, cabozantinib is now the first and only therapy
evaluated in a large, pivotal study in previously treated patients with
advanced renal cell carcinoma to demonstrate a benefit in all three key
efficacy parameters – overall survival, progression-free survival and
objective response rate,” said
In late
On
Both regulatory applications are based on the results of METEOR. In
Cabozantinib is currently marketed in capsule form under the brand name
COMETRIQ® in
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
Secondary endpoints for METEOR include OS and objective response rate.
The secondary endpoint of OS assumed 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 employing a
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. This analysis showed a strong trend in OS favoring
cabozantinib (HR=0.67, 95% CI 0.51-0.89, p=0.005), although the p-value
of 0.0019 to achieve statistical significance was not reached at that
time. Based upon these results and after consulting with the
About Advanced 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 U.S.1 Clear cell RCC 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
Until the introduction of targeted therapies into the RCC setting a decade ago, treatments for metastatic RCC had historically been limited to cytokine therapy (e.g., interleukin-2 and interferon). In the second and later-line settings, which encompass approximately 17,000 drug-eligible patients in the U.S. and 37,000 globally,4 two small-molecule therapies and an immune checkpoint inhibitor have been approved for the treatment of patients with advanced RCC who have received prior systemic therapy. The currently approved small-molecule agents have shown little differentiation in terms of efficacy and have demonstrated only modest progression-free survival benefit in patients refractory to sunitinib, a commonly-used first-line therapy.
The majority of clear cell RCC tumors exhibit down-regulation of
About Cabozantinib
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.
Cabozantinib, marketed under the brand name COMETRIQ®, is
currently approved by the
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 patients.
- 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 patients.
- 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 with COMETRIQ.
- 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, at www.COMETRIQ.com/downloads/Cometriq_Full_Prescribing_Information.pdf
Please refer to the full European Summary of Product Characteristics for
full
About
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including, without limitation, statements related to: acceptance of the latest METEOR results for presentation at a medical meeting later this year; the company’s ability to obtain regulatory approvals of cabozantinib for advanced RCC on an expedited review schedule; and the overall potential of cabozantinib as a treatment for patients with advanced RCC. Words such as “intends,” “will,” “potential” or other similar expressions identify forward-looking statements, but the absence of these words does not necessarily mean that a statement is not forward-looking. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements. 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: risks and
uncertainties related to regulatory review and approval processes and
and COTELLIC is a U.S. trademark.
1Cancer Facts & Figures 2015.
http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf
2Jonasch et al., BMJ (2014) vol. 349, g4797.
3http://www.cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-adult-survival-rates
4ACS 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 (
5Harschman and Choueiri, Cancer J. 2013 v19 316-323; Rankin et al., PNAS, 2014.
6Bommy-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.
7Ciamporcero et al., MolCancerTher, 2014; Rankin et al., PNAS, 2014.
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Source:
Investors Contact:
Exelixis, Inc.
Susan
Hubbard, 650-837-8194
Investor Relations & Corporate
Communications
shubbard@exelixis.com
Media
Contact:
For Exelixis, Inc.
Hal Mackins,
415-994-0040
hal@torchcommunications.com