Data from the COSMIC-021 trial will be
presented on Thursday, February 13, 2020 at the American Society of
Clinical Oncology’s Genitourinary Cancers Symposium
Exelixis, Inc. (NASDAQ:EXEL) today announced encouraging results
from the metastatic castration-resistant prostate cancer (CRPC)
cohort of COSMIC-021, the phase 1b trial of cabozantinib
(CABOMETYX®) in combination with atezolizumab (TECENTRIQ®) in
patients with locally advanced or metastatic solid tumors. The data
will be presented on Thursday, February 13th during Poster Session
A: Prostate Cancer at 11:30 a.m. – 1:00 p.m. PT and 5:30 – 6:30
p.m. PT at the 2020 American Society of Clinical Oncology’s
Genitourinary Cancers Symposium (ASCO GU 2020), which is being held
in San Francisco, California, February 13 – 15, 2020.
Upon enrollment, patients had to have measurable disease per
Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1) and
had progressed on prior novel hormone therapy and could have
received prior docetaxel for hormone sensitive disease. Forty-four
patients were included in this interim analysis. The median follow
up was 12.6 months. The objective response rate (ORR) per RECIST v.
1.1, the trial’s primary endpoint, was 32%, including two complete
responses and 12 partial responses. Disease control rate was 80%.
Among the 36 patients with high-risk clinical features including
visceral metastases and/or extra-pelvic lymph node metastases, the
ORR was 33%. Median duration of response for all responding
patients was 8.3 months. Among 12 patients who had an objective
response and at least one post-baseline prostate-specific antigen
(PSA) evaluation, 67% had a PSA decline of at least 50%.
“Given the poor prognosis for men with metastatic
castration-resistant prostate cancer, measurable visceral disease
and/or extra-pelvic lymph node metastases who have progressed on
novel hormone therapies, we are excited to observe clinically
meaningful activity with the combination of cabozantinib and
atezolizumab in this COSMIC-021 cohort,” said Neeraj Agarwal, M.D.,
Professor, Huntsman Cancer Center, University of Utah, and an
investigator of the trial. “Emerging data suggests a tolerable
safety profile and encouraging efficacy for this combination that
may hold promise for these patients with limited treatment options,
potentially providing patients with more time before the need for
treatment with chemotherapy. We look forward to additional results
as the trial progresses.”
The median treatment duration was 6.3 months (range 1 to 18
months). No new safety signals were identified in this combination
cohort. Treatment-related grade 3/4 adverse events (AEs) occurring
in ≥5% of patients were fatigue (7%), diarrhea (7%) and
hyponatremia (7%). One treatment-related grade 5 AE of dehydration
was reported in a 90-year-old patient. The discontinuation rate of
study treatment for adverse events unrelated to disease progression
was low at 7%.
Exelixis announced on January 7, 2020 that metastatic CRPC
cohort 6 of COSMIC-021 had been expanded to enroll up to 130
patients. Based on regulatory feedback from the U.S. Food &
Drug Administration (FDA), and if supported by the clinical data
from the recently expanded existing cohort and added metastatic
CRPC cohorts, Exelixis intends to file with the FDA for accelerated
approval in a metastatic CRPC indication as early as 2021.
“We’re happy to share these encouraging results from the
metastatic CRPC cohort from COSMIC-021, our first trial evaluating
the combination of cabozantinib and atezolizumab,” said Gisela
Schwab, M.D., President, Product Development and Medical Affairs
and Chief Medical Officer, Exelixis. “We look forward to receiving
data from the most recent expansion of this CRPC cohort while we
are also preparing for the initiation of a phase 3 pivotal trial in
this indication. We are excited about the emerging data in
metastatic CRPC and elsewhere and the potential of combining
cabozantinib with immunotherapies in this and other
difficult-to-treat tumor types.”
More information about this trial is available at
ClinicalTrials.gov.
About the COSMIC-021 Study
COSMIC-021 is a multicenter, phase 1b, open-label study that is
divided into two parts: a dose-escalation phase and an expansion
cohort phase. The dose-escalation phase was designed to enroll
patients either with advanced renal cell carcinoma (RCC) with or
without prior systemic therapy or with inoperable, locally
advanced, metastatic or recurrent urothelial carcinoma (UC),
(including renal, pelvis, ureter, urinary bladder and urethra)
after prior platinum-based therapy. Ultimately, all 12 patients
enrolled in this stage of the trial were patients with advanced
RCC. The dose-escalation phase of the study determined the optimal
dose of cabozantinib to be 40 mg daily when given in combination
with atezolizumab (1200 mg infusion once every 3 weeks). These
results were presented at the European Society for Medical Oncology
2018 Congress.
In the expansion phase, the trial is enrolling 24 cohorts in 12
tumor types: RCC, UC, non-small cell lung cancer (NSCLC), CRPC,
hepatocellular carcinoma (HCC), triple-negative breast cancer,
epithelial ovarian cancer, endometrial cancer, gastric or
gastroesophageal junction adenocarcinoma, colorectal
adenocarcinoma, head and neck cancer, and differentiated thyroid
cancer. Up to 1,720 patients may enroll in this phase of the trial:
each expansion cohort will initially enroll approximately 30
patients, and up to 10 cohorts may further expand enrollment
resulting in up to 1,000 patients across such potential additional
expansion cohorts.
Four of the cohorts are exploratory: three are enrolling
approximately 30 patients each with advanced UC, CRPC or NSCLC to
be treated with cabozantinib as a single-agent, and one is
enrolling approximately 10 patients with advanced CRPC to be
treated with single-agent atezolizumab. Exploratory cohorts have
the option to be expanded up to 80 patients (cabozantinib) and 30
patients (atezolizumab) total.
Exelixis is the study sponsor of COSMIC-021. Ipsen has opted in
to participate in the trial and is contributing to the funding for
this study under the terms of the companies’ collaboration
agreement. Roche is providing atezolizumab for the trial.
About CRPC
According to the American Cancer Society, approximately 192,000
new cases of prostate cancer will be diagnosed and 33,000 people
will die from the disease this year.1 Prostate cancer that has
spread beyond the prostate and does not respond to
androgen-suppression therapies — a common treatment for prostate
cancer — is known as metastatic CRPC.2 Researchers estimate that in
2020, 43,000 people with prostate cancer will progress to
metastatic CRPC, which has a median survival of less than two
years.3,4,5
About CABOMETYX® (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of
patients with advanced RCC and for the treatment of patients with
HCC who have been previously treated with sorafenib. CABOMETYX
tablets have also received regulatory approvals in the European
Union and additional countries and regions worldwide. In 2016,
Exelixis granted Ipsen exclusive rights for the commercialization
and further clinical development of cabozantinib outside of the
United States and Japan. In 2017, Exelixis granted exclusive rights
to Takeda Pharmaceutical Company Limited for the commercialization
and further clinical development of cabozantinib for all future
indications in Japan.
Important Safety Information
Warnings and Precautions
Hemorrhage: Severe and fatal hemorrhages occurred with
CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5%
in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX
for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to
patients who have a recent history of hemorrhage, including
hemoptysis, hematemesis, or melena.
Perforations and Fistulas: Gastrointestinal (GI)
perforations, including fatal cases, occurred in 1% of CABOMETYX
patients. Fistulas, including fatal cases, occurred in 1% of
CABOMETYX patients. Monitor patients for signs and symptoms of
perforations and fistulas, including abscess and sepsis.
Discontinue CABOMETYX in patients who experience a Grade 4 fistula
or a GI perforation.
Thrombotic Events: CABOMETYX increased the risk of
thrombotic events. Venous thromboembolism occurred in 7% (including
4% pulmonary embolism) and arterial thromboembolism in 2% of
CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX
patients. Discontinue CABOMETYX in patients who develop an acute
myocardial infarction or serious arterial or venous thromboembolic
event requiring medical intervention.
Hypertension and Hypertensive Crisis: CABOMETYX can cause
hypertension, including hypertensive crisis. Hypertension occurred
in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do
not initiate CABOMETYX in patients with uncontrolled hypertension.
Monitor blood pressure regularly during CABOMETYX treatment.
Withhold CABOMETYX for hypertension that is not adequately
controlled with medical management; when controlled, resume at a
reduced dose. Discontinue CABOMETYX for severe hypertension that
cannot be controlled with anti-hypertensive therapy or for
hypertensive crisis.
Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients.
Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold
CABOMETYX until improvement to Grade 1 and resume at a reduced dose
for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be
managed with standard antidiarrheal treatments, or Grade 4
diarrhea.
Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in
44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX
patients. Withhold CABOMETYX until improvement to Grade 1 and
resume at a reduced dose for intolerable Grade 2 PPE or Grade 3
PPE.
Proteinuria: Proteinuria occurred in 7% of CABOMETYX
patients. Monitor urine protein regularly during CABOMETYX
treatment. Discontinue CABOMETYX in patients who develop nephrotic
syndrome.
Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of
CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis,
osteitis, bone erosion, tooth or periodontal infection, toothache,
gingival ulceration or erosion, persistent jaw pain, or slow
healing of the mouth or jaw after dental surgery. Perform an oral
examination prior to CABOMETYX initiation and periodically during
treatment. Advise patients regarding good oral hygiene practices.
Withhold CABOMETYX for at least 3 weeks prior to scheduled dental
surgery or invasive dental procedures, if possible. Withhold
CABOMETYX for development of ONJ until complete resolution.
Impaired Wound Healing: Wound complications occurred with
CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to
elective surgery. Do not administer CABOMETYX for at least 2 weeks
after major surgery and until adequate wound healing is observed.
The safety of resumption of CABOMETYX after resolution of wound
healing complications has not been established.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS):
RPLS, a syndrome of subcortical vasogenic edema diagnosed by
characteristic findings on MRI, can occur with CABOMETYX. Evaluate
for RPLS in patients 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.
Advise pregnant women and females of reproductive potential of the
potential risk to a fetus. Verify the pregnancy status of females
of reproductive potential prior to initiating CABOMETYX and advise
them to use effective contraception during treatment and for 4
months after the last dose.
Adverse Reactions
The most commonly reported (≥25%) adverse reactions are:
diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension,
and vomiting.
Drug Interactions
Strong CYP3A4 Inhibitors: If coadministration with strong
CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
Avoid grapefruit or grapefruit juice.
Strong CYP3A4 Inducers: If coadministration with strong
CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
Avoid St. John’s wort.
USE IN SPECIFIC POPULATIONS
Lactation: Advise women not to breastfeed during
CABOMETYX treatment and for 4 months after the final dose.
Hepatic Impairment: In patients with moderate hepatic
impairment, reduce the CABOMETYX dosage. CABOMETYX is not
recommended for use in patients with severe hepatic impairment.
Please see accompanying full Prescribing Information:
https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
About Exelixis
Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially
successful, oncology-focused biotechnology company that strives to
accelerate the discovery, development and commercialization of new
medicines for difficult-to-treat cancers. Following early work in
model system genetics, we established a broad drug discovery and
development platform that has served as the foundation for our
continued efforts to bring new cancer therapies to patients in
need. Our discovery efforts have resulted in four commercially
available products, CABOMETYX® (cabozantinib), COMETRIQ®
(cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO®
(esaxerenone), and we have entered into partnerships with leading
pharmaceutical companies to bring these important medicines to
patients worldwide. Supported by revenues from our marketed
products and collaborations, we are committed to prudently
reinvesting in our business to maximize the potential of our
pipeline. We are supplementing our existing therapeutic assets with
targeted business development activities and internal drug
discovery — all to deliver the next generation of Exelixis
medicines and help patients recover stronger and live longer.
Exelixis is a member of the Standard & Poor’s (S&P) MidCap
400 index, which measures the performance of profitable mid-sized
companies. For more information about Exelixis, please visit
www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis,
Inc. on Facebook.
Forward-Looking Statements
This press release contains forward-looking statements,
including, without limitation, statements related to: Exelixis’
expectation that data from the CRPC cohort of the COSMIC-021 trial
will be presented at ASCO GU 2020; the therapeutic potential of
cabozantinib in combination with atezolizumab for patients with
CRPC and other difficult-to-treat tumor types; Exelixis’ intention
to file with the FDA for accelerated approval of the combination of
cabozantinib and atezolizumab in a metastatic CRPC indication as
early as 2021, based on regulatory feedback from the FDA and if
supported by the clinical data; Exelixis’ plans to initiate a phase
3 pivotal trial in metastatic CRPC; and Exelixis’ plans to reinvest
in its business to maximize the potential of the company’s
pipeline, including through targeted business development
activities and internal drug discovery. Any statements that refer
to expectations, projections or other characterizations of future
events or circumstances are forward-looking statements and 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 availability
of data at the referenced times; risks and uncertainties related to
regulatory review and approval processes and Exelixis’ compliance
with applicable legal and regulatory requirements; the potential
failure of the combination of cabozantinib and atezolizumab to
demonstrate safety and/or efficacy in future trials; uncertainties
inherent in the product development process; the costs of
conducting clinical trials, including the ability or willingness of
Exelixis’ collaboration partners to invest in the resources
necessary to complete the trials; Exelixis’ dependence on
third-party vendors for the development, manufacture and supply of
cabozantinib; Exelixis’ ability to protect its intellectual
property rights; market competition, including the potential for
competitors to obtain approval for generic versions of CABOMETYX;
changes in economic and business conditions; and other factors
affecting Exelixis and its development programs discussed under the
caption “Risk Factors” in Exelixis’ Quarterly Report on Form 10-Q
filed with the Securities and Exchange Commission (SEC) on October
30, 2019, and in Exelixis’ future filings with the SEC. All
forward-looking statements in this press release are based on
information available to Exelixis as of the date of this press
release, and Exelixis undertakes no obligation to update or revise
any forward-looking statements contained herein.
Exelixis, the Exelixis logo, CABOMETYX,
COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a
Japanese trademark.
TECENTRIQ® (atezolizumab) is a registered
trademark of Genentech, a member of the Roche Group.
_______________________________ 1 American Cancer Society. Key
Statistics for Prostate Cancer. Available at:
https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html.
Accessed February 2020. 2 American Society of Clinical Oncology.
Cancer.Net. Treatment of Metastatic Castration-Resistant Prostate
Cancer. September 8, 2014. Available at:
https://www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer.
Accessed February 2020. 3 Scher, H.I., Solo, K., Valant, J., Todd,
M.B., Mehra, M. Prevalence of Prostate Cancer Clinical States and
Mortality in the United States: Estimates Using a Dynamic
Progression Model. PLOS ONE. 2015; 10: e0139440. 4 American
Urological Association. Prostate Cancer: Castration Resistant
Guideline. 2018. Available at:
https://www.auanet.org/guidelines/prostate-cancer-castration-resistant-guideline.
Accessed February 2020. 5 Moreira, D. M., Howard, L. E., Sourbeer,
K. N., et al. Predicting Time From Metastasis to Overall Survival
in Castration-Resistant Prostate Cancer: Results From SEARCH. Clin
Genitourin Cancer. 2017; 15: 60–66.e2.
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version on businesswire.com: https://www.businesswire.com/news/home/20200210005731/en/
Investors: Susan Hubbard EVP, Public Affairs and Investor
Relations Exelixis, Inc. (650) 837-8194 shubbard@exelixis.com
Media: Lindsay Treadway Senior Director, Public Affairs
and Advocacy Relations Exelixis, Inc. (650) 837-7522
ltreadway@exelixis.com
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