Press Release
Press Release
Exelixis-discovered Compounds To Be Featured in 15 Presentations at the ESMO 2016 Congress
- CABOSUN results accepted as late-breaker presentation in oral
session on
Detailed results from CABOSUN, a randomized phase 2 clinical trial of
cabozantinib compared with sunitinib in patients with previously
untreated advanced renal cell carcinoma (RCC), will be presented at ESMO
as a late-breaking abstract in the Genitourinary Tumours, Non-Prostate
oral presentation session on
“This year’s
Cabozantinib to be featured in eight presentations
The full
schedule of cabozantinib presentations expected at the meeting is as
follows:
Oral Presentation
[LBA30]
“CABOzantinib versus SUNitinib (CABOSUN) as initial targeted therapy for
patients with metastatic renal cell carcinoma (mRCC) of poor and
intermediate risk groups: Results from ALLIANCE A031203 Trial.”
Dr.
Session:
Genitourinary Tumours, Non-Prostate
Oral presentation
Note: This is a
National Cancer Institute Cancer Therapy Evaluation Program (NCI-CTEP)
study.
Poster Discussion
[774PD]
“A phase I study of cabozantinib plus nivolumab (CaboNivo) in
patients (pts) with refractory metastatic urothelial carcinoma (mUC) and
other genitourinary (GU) tumors.”
Dr.
Session:
Genitourinary Tumours, Non-Prostate
Poster presented
Note: This is an
NCI-CTEP study.
Poster Presentations
[787P]
“A phase II study of cabozantinib in patients (pts) with
relapsed/refractory metastatic urothelial carcinoma (mUC).”
Dr.
Session: Genitourinary
Tumours, Non-Prostate
Poster presented
Note: This is an NCI-CTEP study.
[814P] “Efficacy of cabozantinib (cabo) vs everolimus (eve) by
metastatic site and tumor burden in patients (pts) with advanced renal
cell carcinoma (RCC) in the phase 3 METEOR trial.”
Dr.
Session: Genitourinary Tumours, Non-Prostate
Poster
presented
[815P] “Evaluation of the novel “trial within a trial” design
of METEOR, a randomized phase 3 trial of cabozantinib versus everolimus
in patients (pts) with advanced renal cell carcinoma (RCC).”
Session:
Genitourinary Tumours, Non-Prostate
Poster presented
[816P] “Quality of life (QoL) in the phase 3 METEOR trial of
cabozantinib vs everolimus for advanced renal cell carcinoma (RCC).”
Dr.
Session:
Genitourinary Tumours, Non-Prostate
Poster presented
[818P] “Analysis of regional differences in the phase 3 METEOR
study of cabozantinib (cabo) versus everolimus (eve) in advanced renal
cell carcinoma (RCC).”
Dr.
Session:
Genitourinary Tumours, Non-Prostate
Poster presented
[1421TiP] “A randomized double-blind phase II study evaluating the
role of maintenance therapy with cabozantinib in high grade
undifferentiated uterine sarcoma (HGUS) after stabilization or response
to doxorubicin +/- ifosfamide following surgery or in metastatic first
line treatment.”
Dr.
Session: Sarcoma
Poster presented
Note: This is an
investigator-sponsored trial.
Cobimetinib to be featured in seven presentations
Also at
the meeting, Exelixis’ collaborator Genentech, a member of the
Oral Presentation
[1111O]
“Genomic features of complete responders (CR) versus fast progressors
(PD) in patients with BRAFV600-mutated metastatic melanoma treated with
cobimetinib + vemurafenib or vemurafenib alone.”
Y. Yan,
Session:
Melanoma and Other Skin Tumours
Oral presentation
Poster Discussion
[1109PD]
“Preliminary safety and clinical activity of atezolizumab combined
with cobimetinib and vemurafenib in BRAF V600-mutant metastatic
melanoma.”
Dr.
Session: Melanoma and Other Skin Tumours
Poster
presented
Poster Presentations
[470P]
“Efficacy and safety of cobimetinib (cobi) and atezolizumab (atezo)
in an expanded phase 1B study of microsatellite-stable (MSS) metastatic
colorectal cancer (mCRC).”
Dr.
Session: Genitourinary Tumours,
Colorectal
Poster presented
[1142P] “Prognostic subgroups and impact of treatment for
post-progression overall survival (ppOS) in patients (pts) with
BRAFV600-mutated metastatic melanoma treated with decarbazine (DTIC) or
vemurafenib (VEM) +/- cobimetinib (COBI): A pooled analysis.”
Dr.
Session: Melanoma and Other Skin Tumours
Poster
presented
[1138P] “Cobimetinib plus vemurafenib to treat unresectable or
metastatic melanoma: Data from the French temporary authorization for
use.”
Dr.
Session: Melanoma and Other Skin Tumours
Poster
presented
[1156TiP] “CONVERCE: Evaluation of cobimetinib and vemurafenib
combination treatment in patients with brain metastases from BRAFV600
mutated melanoma.”
Dr.
Session: Melanoma and Other Skin Tumours
Poster
presented
[286P] “First-line cobimetinib (C) + paclitaxel (P) in
patients (pts) with advanced triple-negative breast cancer (TNBC):
Updated results and tumoral immune cell infiltration data from the phase
2 COLET study.”
Dr.
Session: Breast Cancer, Locally Advanced
and Metastatic
Poster presented
About the CABOSUN Study
On
CABOSUN is a randomized, open-label, active-controlled phase 2 trial that enrolled 157 patients with advanced RCC determined to be intermediate- or poor-risk by the International Metastatic RCC Database Consortium (IMDC) criteria. Patients were randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off). The primary endpoint was progression-free survival. Secondary endpoints included overall survival and objective response rate. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2, and had to be intermediate or poor risk, per the IMDC Criteria (Heng JCO 2009). Prior systemic treatment for RCC was not permitted.
Please see Important Safety Information below and full U.S. prescribing information at https://cabometyx.com/downloads/cabometyxuspi.pdf.
About Advanced Renal Cell Carcinoma
The American Cancer Society’s 2016 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; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12 percent, with no identified cure for the disease. 1 Approximately 30,000 patients in the U.S. and 68,000 globally require treatment.3
The majority of clear cell RCC tumors have lower than normal levels of a
protein called
About CABOMETYX™ (cabozantinib)
CABOMETYX is the tablet formulation of cabozantinib. Its targets include MET, AXL and VEGFR-1, -2 and -3. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.
CABOMETYX is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.
On
On
Important Safety Information
Hemorrhage: Severe hemorrhage occurred with CABOMETYX. The incidence of Grade ≥3 hemorrhagic events was 2.1% in CABOMETYX-treated patients and 1.6% in everolimus-treated patients. Fatal hemorrhages also occurred in the cabozantinib clinical program. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
Gastrointestinal (GI) Perforations and Fistulas: Fistulas were reported in 1.2% (including 0.6% anal fistula) of CABOMETYX-treated patients and 0% of everolimus-treated patients. GI perforations were reported in 0.9% of CABOMETYX-treated patients and 0.6% of everolimus-treated patients. Fatal perforations occurred in the cabozantinib clinical program. Monitor patients for symptoms of fistulas and perforations. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.
Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. Venous thromboembolism was reported in 7.3% of CABOMETYX-treated patients and 2.5% of everolimus-treated patients. Pulmonary embolism occurred in 3.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Events of arterial thromboembolism were reported in 0.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension. Hypertension was reported in 37% (15% Grade ≥3) of CABOMETYX-treated patients and 7.1% (3.1% Grade ≥3) of everolimus-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.
Diarrhea: Diarrhea occurred in 74% of patients treated with CABOMETYX and in 28% of patients treated with everolimus. Grade 3 diarrhea occurred in 11% of CABOMETYX-treated patients and in 2% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to diarrhea occurred in 26% of patients.
Palmar-Plantar Erythrodysesthesia Syndrome (PPES): Palmar-plantar erythrodysesthesia syndrome (PPES) occurred in 42% of patients treated with CABOMETYX and in 6% of patients treated with everolimus. Grade 3 PPES occurred in 8.2% of CABOMETYX-treated patients and in <1% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPES or Grade 3 PPES until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to PPES occurred in 16% of patients.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
Embryo-fetal Toxicity: CABOMETYX can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, PPES, hypertension, vomiting, weight decreased, and constipation.
Drug Interactions: Strong CYP3A4 inhibitors and inducers: Reduce the dosage of CABOMETYX if concomitant use with strong CYP3A4 inhibitors cannot be avoided. Increase the dosage of CABOMETYX if concomitant use with strong CYP3A4 inducers cannot be avoided.
Lactation: Advise a lactating woman not to breastfeed during treatment with CABOMETYX and for 4 months after the final dose.
Reproductive Potential: Contraception―Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the final dose. Infertility ―CABOMETYX may impair fertility in females and males of reproductive potential.
Hepatic Impairment: Reduce the CABOMETYX dose in patients with mild (Child-Pugh score [C-P] A) or moderate (C-P B) hepatic impairment. CABOMETYX is not recommended for use in patients with severe hepatic impairment.
Please see full Prescribing Information at https://cabometyx.com/downloads/cabometyxuspi.pdf.
About the Cobimetinib and Vemurafenib Combination
Cobimetinib is a selective inhibitor that blocks the activity of MEK, a
protein kinase that is part of a key pathway (the RAS-RAF-MEK-ERK
pathway) that promotes cell division and survival. This pathway is
frequently activated in human cancers including melanoma, where mutation
of one of its components (BRAF) causes abnormal activation in about 50%
of cases. Tumors with BRAF mutations may develop resistance and
subsequently progress after treatment with a BRAF inhibitor. About 50%
of patients with BRAF mutation positive melanoma experience a tumor
response when treated with a BRAF inhibitor, however development of
resistance and subsequent tumor progression limits treatment benefit.
Clinical and preclinical analyses indicated that reactivation of the
MEK-ERK pathway may underlie development of resistance to BRAF
inhibitors in many progressing tumors, and that co-treatment with a BRAF
and MEK inhibitor delays the emergence of resistance in the preclinical
setting, providing the rationale for testing the combination of
vemurafenib and cobimetinib in clinical trials.
About
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: future data presentations
from clinical trials of cabozantinib and cobimetinib at ESMO, including
detailed results from CABOSUN; the opportunity for
References | |||
1. | American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society; 2016. | ||
2. | Jonasch E., Gao J., Rathmell W.K., Renal cell carcinoma. BMJ. 2014; 349:g4797. | ||
3. | Decision Resources Report: Renal Cell Carcinoma. October 2014 (internal data on file). | ||
4. | Harshman, L.C. and Choueiri, T.K., Targeting the hepatocyte growth factor/c-Met signaling pathway in renal cell carcinoma. Cancer J. 2013; 19(4):316-23. | ||
5. | Rankin et al., Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET. Proc Natl Acad Sci U S A. 2014; 111(37):13373-8. | ||
6. | Zhou L, Liu X-D, Sun M, et al. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma. Oncogene. 2015 Sep 14. doi:10.1038/onc.2015.343. [Epub ahead of print]. | ||
7. | Koochekpour et al.,The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells. Mol Cell Biol. 1999; 19(9):5902–5912. | ||
8. | Takahashi A, Sasaki H, Kim SJ, et al. Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. Cancer Res. 1994;54:4233-4237. | ||
9. | Nakagawa M, Emoto A, Hanada T, Nasu N, Nomura Y. Tubulogenesis by microvascular endothelial cells is mediated by vascular endothelial growth factor (VEGF) in renal cell carcinoma. Br J Urol. 1997;79:681-687. |
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Source:
Exelixis, Inc.
Investors:
Susan Hubbard,
650-837-8194
Public Affairs and Investor Relations
shubbard@exelixis.com
or
Media:
Lindsay
Treadway, 650-837-7522
Public Affairs and Advocacy Relations
ltreadway@exelixis.com