|Exelixis-Discovered Compounds to Be Featured in 10 Presentations at ESMO 2017 Congress|
- CABOSUN overall survival results and independent radiology review
committee analysis of progression-free survival data to be presented
during poster discussion session on
Progression-free survival by independent radiology review and updated
overall survival 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 as a late-breaking abstract in the Genitourinary Tumours,
Non-Prostate poster discussion session on
“We look forward to this year’s
Cabozantinib to be featured in eight presentations
The full schedule of cabozantinib presentations expected at the meeting is as follows:
[846O] “Final results of a phase I study of cabozantinib (Cabo) plus
nivolumab (Nivo) and CaboNivo plus Ipilimumab (Ipi) in patients (pts)
with metastatic urothelial carcinoma (mUC) and other genitourinary (GU)
[LBA38] “Progression-free survival (PFS) by independent review and
updated overall survival (OS) results from Alliance A031203 trial
(CABOSUN): cabozantinib versus sunitinib as initial targeted therapy for
patients (pts) with metastatic renal cell carcinoma (mRCC)”
[872P] “Outcomes based on plasma biomarkers in METEOR, a randomized
phase 3 trial of cabozantinib (C) vs everolimus (E) in advanced renal
cell carcinoma (RCC)”
[876P] “Efficacy of cabozantinib (C) after PD-1/PD-L1 checkpoint
inhibitors in metastatic renal cell carcinoma (mRCC): the Gustave Roussy
[891P] “Outcomes of patients with metastatic renal cell carcinoma
(mRCC) who were treated with second-line (2L) vascular endothelial
growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) after
first-line (1L) immune checkpoint inhibitor (ICI) therapy”
[901P] “Safety and efficacy of cabozantinib for metastatic renal cell
carcinoma (mRCC): real world data from an Italian Expanded Access
[912P] “Cabozantinib for the treatment of patients with metastatic
variant histology renal cell carcinoma (vhRCC): a retrospective study”
[927TiP] “Cabozantinib in patients with advanced penile squamous cell
carcinoma (PSCC): the open-label, single-arm, single-center, phase 2,
Cobimetinib to be featured in two presentations
Also at the congress, Exelixis’ collaborator Genentech, a member of the
[1225PD] “Prognostic impact of early complete metabolic response on
FDG-PET, in BRAF V600 mutant metastatic melanoma patients treated with
combination vemurafenib & cobimetinib”
[1241P] “Impact of duration of response (DOR) on overall survival
(OS) in patients with metastatic melanoma treated with dacarbazine
(DTIC), vemurafenib (V), or cobimetinib plus vemurafenib (C+V): a pooled
About the CABOSUN Study
CABOSUN was 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 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 PFS. 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).2 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 Genitourinary Cancers
Genitourinary cancers are those that affect the urinary tract, bladder, kidneys, ureter, prostate, testicles, penis or adrenal glands — parts of the body involved in reproduction and excretion — and include renal cell carcinoma (RCC) and urothelial carcinoma.3
The American Cancer Society’s 2017 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.4 Clear cell RCC is the most common type of kidney cancer in adults.5 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.6 Approximately 30,000 patients in the U.S. and 68,000 globally require treatment, and an estimated 14,000 patients in the U.S. each year are in need of a first-line treatment for advanced kidney cancer.7
Urothelial cancers encompass carcinomas of the bladder, ureter and renal pelvis at a ratio of 50:3:1, respectively.8 Urothelial carcinoma occurs mainly in older people, with 90 percent of patients aged 55 or older.9 Bladder cancer is the fourth most common cancer in men and accounts for about five percent of all new cases of cancer in the U.S. each year.9 In 2013, an estimated 587,426 people were living with bladder cancer in the U.S.10
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.
CABOMEYX is not indicated for the treatment of previously untreated advanced RCC.
U.S. 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.
About the Cobimetinib and Vemurafenib Combination
Cobimetinib is a reversible 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.
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; Exelixis’
commitment to advancing the company’s ongoing clinical research program
to help improve care and outcomes for patients with cancer; Ipsen’s
confirmation of its intent to submit the regulatory dossier for
cabozantinib as a treatment for first-line advanced RCC in the
1. Choueiri, T.K., et al. Cabozantinib Versus Sunitinib As
Initial Targeted Therapy for Patients With Metastatic Renal Cell
Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN
2. Heng D.Y., Xie W., Regan M.M., et al. Prognostic factors for overall
survival in patients with metastatic renal cell carcinoma treated with
vascular endothelial growth factor-targeted agents: Results from a
large, multicenter study.
5. Jonasch, E., Gao, J., Rathmell, W., Renal cell carcinoma. BMJ. 2014; 349:g4797.
6. Ko, J. , Choueiri, T., et al. First-, second- third-line therapy for
mRCC: benchmarks for trial design from the IMDC.
7. Decision Resources Report: Renal Cell Carcinoma.
8. Hurwitz, M. et al. Urothelial and Kidney Cancers. Cancer Management. http://www.cancernetwork.com/cancer-management/urothelial-and-kidney-cancers.