Press Release
Press Release
Exelixis Presents COMETRIQ™ (cabozantinib) Clinical Trial Data in Patients with Progressive, Metastatic Medullary Thyroid Cancer
-- 30% of patients in a phase 1 study remain progression-free for more than two years --
--
“These data provide important insight into the clinical utility of
COMETRIQ in patients with progressive, metastatic MTC, the first
indication in which this tyrosine kinase inhibitor has been approved,”
said
“These results are encouraging for the field of medullary thyroid cancer because, for many years, patients with this disease have had limited treatment options,” said Dr. Cohen. “These results show that a significant number of patients treated with cabozantinib achieved meaningful long-term disease control and were able to remain on continuous daily therapy.”
Dr.
“These data show that COMETRIQ improves PFS in all RET subgroups,” said Dr. Sherman. “The extent of the benefit varies in part based on tumor genotype. Given that RET mutations are associated with most cases of hereditary MTC and about half of sporadic cases, understanding the correlation between specific RET mutations and response to COMETRIQ may be important for optimizing outcomes in patients with metastatic MTC. Recent data have shown RAS mutations in subsets of patients without RET mutations, and the data from our study show that these patients also benefit from treatment with COMETRIQ. These findings are important for improving outcomes and PFS for patients with metastatic MTC.”
About COMETRIQ
COMETRIQ’s safety and efficacy was assessed in an international, multi-center, randomized double-blinded controlled trial called EXAM of 330 patients with progressive, metastatic medullary thyroid carcinoma (MTC). Patients were required to have evidence of actively progressive disease within 14 months prior to study entry confirmed by an Independent Radiology Review Committee (IRRC) masked to treatment assignment (89%) or the treating physician (11%). Patients were randomized (2:1) to receive COMETRIQ 140 mg (n = 219) or placebo (n = 111) orally, once daily until disease progression determined by the treating physician or until intolerable toxicity. Randomization was stratified by age (≤65 years vs. > 65 years) and prior use of a tyrosine kinase inhibitor (TKI). No crossover was allowed at the time of progression. The main efficacy outcome measures of PFS, objective response and response duration were based on IRRC-confirmed events using the modified RECIST criteria.
A statistically significant prolongation in PFS was demonstrated among COMETRIQ-treated patients compared to those receiving placebo [HR 0.28 (95% CI: 0.19, 0.40); p<0.0001], with median PFS times of 11.2 months and 4.0 months in the COMETRIQ and placebo arms, respectively. Partial responses were observed only among patients in the COMETRIQ arm (27% vs 0; p<0.0001). The median duration of objective responses was 14.7 months (95% CI: 11.1, 19.3) for patients treated with COMETRIQ. There was no statistically significant difference in overall survival between the treatment arms at the planned interim analysis.
COMETRIQ Mechanism of Action
COMETRIQ (cabozantinib) inhibits the activity of tyrosine kinases including RET, MET and VEGFR2. 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™ Important Safety Information, including Boxed Warning
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 (PPE) Syndrome 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.
- 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.
Drug Interactions – COMETRIQ is a CYP3A4 substrate. Co-administration of strong CYP3A4 inhibitors can increase cabozantinib exposure. Chronic co-administration of strong CYP3A4 inducers can reduce cabozantinib exposure.
For full prescribing information, including Boxed Warning, please visit www.COMETRIQ.com.
About
Forward-Looking Statements
This press release contains forward-looking statements, including,
without limitation, statements related to: the continued development and
clinical, therapeutic and commercial potential of, and opportunities
for, COMETRIQ; the belief that the referenced data provide important
insight into the clinical utility of COMETRIQ in patients with
progressive, metastatic MTC; the belief that COMETRIQ offers patients an
important new treatment option that can lead to durable disease control;
the belief that the referenced analyses provide additional rationale for
exploring the clinical utility of COMETRIQ in other tumor types with
genetic alterations in the RET and RAS genes; the belief that the
referenced results provide physicians and patients with additional
information showing that COMETRIQ can help improve long-term disease
control; the belief that understanding the correlation between specific
RET mutations and response to COMETRIQ may be important for optimizing
outcomes in patients with metastatic MTC; and the belief that the
referenced findings are important for improving outcomes and PFS for
patients with metastatic MTC. Words such as “show,” “provide,”
“insight,” “supporting,” “evidence,” “offers,” “can,” “believe,”
“rationale,” “investigating,” “activity,” “encouraging,” “may,”
“important,” and similar expressions are intended to identify
forward-looking statements. These forward-looking statements are based
upon
Source:
Exelixis, Inc.
Charles Butler, 650-837-7277
Vice President,
Investor Relations and Corporate Communications
cbutler@exelixis.com