– Data from three cohorts of phase 1b
COSMIC-021 trial to be presented during the 2020 American Society
of Clinical Oncology Virtual Scientific Program (ASCO20) –
– 27% objective response rate seen in immune
checkpoint inhibitor-pretreated non-small cell lung cancer cohort 7
–
– Phase 3 pivotal trials planned for
advanced non-small cell lung cancer and metastatic
castration-resistant prostate cancer –
Exelixis, Inc. (NASDAQ: EXEL) today announced phase 1b clinical
trial results for the combination of cabozantinib (CABOMETYX®) and
atezolizumab (TECENTRIQ®) in patients with locally advanced or
metastatic solid tumors. The data from three expansion cohorts of
the COSMIC-021 trial will be presented during the 2020 American
Society of Clinical Oncology Virtual Scientific Program (ASCO20).
Results from the non-small cell lung cancer (NSCLC) and the
metastatic castration-resistant prostate cancer (CRPC) cohorts will
be presented as posters, and results from the urothelial carcinoma
(UC) cohort will be presented as a poster discussion; all three
presentations will be available on demand for ASCO20 registrants
beginning Friday, May 29 at 8:00 a.m. ET.
NSCLC Expansion Cohort (abstract
9610):
Initial results from the NSCLC expansion cohort (cohort 7) will
be presented by Joel Neal, M.D., Ph.D., Associate Professor of
Medicine – Oncology at the Stanford University School of Medicine,
one of the lead trial investigators. The analysis included 30
patients who had received prior therapy with immune checkpoint
inhibitors, and 87% of patients had received prior chemotherapy.
Fifty percent of patients received the cabozantinib and
atezolizumab combination as their second line of therapy and 50% as
their third line of therapy. At the time of enrollment in the
study, the best response to prior immune checkpoint inhibitor
therapy was a partial response in 3 (10%) patients, stable disease
in 7 (23%) patients, progressive disease in 14 (47%) patients and
unknown in 5 (17%) patients.
At a median follow-up of 12.1 months, the investigator-assessed
confirmed objective response rate (ORR) per Response Evaluation
Criteria in Solid Tumors (RECIST) v. 1.1, the trial’s primary
endpoint, was 27%, and the disease control rate was 83%. Median
progression-free survival (PFS) was 4.2 months (95% confidence
interval [CI] 2.7–7 months) with 22 events (73%), and median
duration of response for all responding patients was 5.7
months.
“Cabozantinib, in combination with immune checkpoint inhibitors,
has now demonstrated promise in multiple difficult to treat tumor
types,” said Dr. Sumanta Pal, Clinical Professor, City of Hope, the
principal investigator for the COSMIC-021 study. “The findings from
the three COSMIC-021 cohorts presented at ASCO20 add to the growing
body of evidence of potential synergistic effects with cabozantinib
and immune checkpoint inhibitors. We are particularly encouraged by
the new data emerging from the NSCLC cohort which showed a 27%
confirmed overall response rate, including three patients with
primary refractory disease to checkpoint inhibition. Further
evaluation of cabozantinib and atezolizumab in patients with
advanced tumor types, including immune checkpoint
inhibitor-pretreated NSCLC, and forms of prostate and urothelial
cancers, is warranted.”
The most common treatment-related adverse events (AEs) were
diarrhea (53%), fatigue (37%), nausea (30%), decreased appetite
(23%), palmar-plantar erythrodysesthesia (20%) and vomiting (20%).
One patient experienced grade 5 pneumonitis that was related to
atezolizumab, and one patient (3%) discontinued due to
treatment-related AEs not associated with disease progression.
“We are encouraged by these promising findings in patients with
non-small cell lung cancer who had been previously treated with
immune checkpoint inhibitor therapy, along with other COSMIC-021
results presented at ASCO20,” said Gisela Schwab, M.D., President,
Product Development and Medical Affairs and Chief Medical Officer,
Exelixis. “The efficacy data and favorable safety profiles seen in
the three cohorts suggest the combination of cabozantinib and
atezolizumab offers promise for patients with advanced,
difficult-to-treat tumor types. These findings and additional data
from these cohorts will inform the design of future studies,
including planned phase 3 pivotal trials for the combination of
cabozantinib and atezolizumab in advanced or metastatic NSCLC and
CRPC.”
UC Expansion Cohort (abstract
5013):
Initial results from the UC expansion cohort (cohort 2) will be
presented by Dr. Pal. The analysis included 30 patients who had
been previously treated with platinum-containing chemotherapy, with
a median follow-up of 19.7 months. The investigator-assessed ORR
per RECIST v. 1.1 was 27%, with two complete responses; disease
control rate was 63%. Median duration of response was not yet
reached, and the longest ongoing response was 15.6 months. Median
PFS was 5.4 months. Preliminary data did not suggest an association
between PD-L1 expression and tumor response.
The most common treatment-related AEs were asthenia (37%),
diarrhea (27%), decreased appetite (23%), increased transaminases
(23%) and mucosal inflammation (20%). No discontinuations due to
treatment-related AEs occurred.
CRPC Expansion Cohort (abstract
5564):
An interim analysis from the metastatic CRPC expansion cohort
(cohort 6) was previously presented at the 2020 American Society of
Clinical Oncology’s Genitourinary Cancers Symposium and was now
updated with additional biomarker results that will be presented by
Neeraj Agarwal, M.D., Professor, Huntsman Cancer Center, University
of Utah, and an investigator of the trial. This analysis of 44
patients who had been previously treated with enzalutamide and/or
abiraterone found an ORR per RECIST v. 1.1 of 32% and a disease
control rate of 80% at a median follow up of 15.8 months.
Preliminary data from the analysis did not suggest an association
between PD-L1 expression and antitumor activity, suggesting
patients with or without PD-L1 may respond to treatment with the
combination of cabozantinib plus atezolizumab. Comparison of
baseline and circulating immune cell counts after 21 days showed a
total increase in circulating T cells (CTLs) and a decrease in
immunosuppressive cells. Subpopulations of CTLs also increased with
the largest accumulation observed for prolonged activated CTLs.
Additional safety and efficacy findings from this analysis were
previously presented at the 2020 American Society of Clinical
Oncology’s Genitourinary Cancers Symposium.
Based on regulatory feedback from the U.S. Food & Drug
Administration (FDA), and if supported by the clinical data,
Exelixis intends to file with the FDA for accelerated approval in a
metastatic CRPC indication as early as 2021.
More information about COSMIC-021 is available at
ClinicalTrials.gov (NCT03170960).
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 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, 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 NSCLC
Lung cancer is the second most common type of cancer in the
U.S., with more than 220,000 new cases expected to be diagnosed in
2020.1 The disease is the leading cause of cancer-related mortality
in both men and women, causing 25% of all cancer-related deaths.1
The majority (84%) of lung cancer cases are NSCLC, which mainly
comprise adenocarcinoma, squamous cell carcinoma and large cell
carcinoma.1 The five-year survival rate for patients with NSCLC is
24%, but that rate falls to just 6% for those with advanced or
metastatic disease.2 More than half of lung cancer cases are
diagnosed at an advanced stage,3 and more options are needed for
these patients.
About UC
Urothelial cancers encompass carcinomas of the bladder, ureter
and renal pelvis at a ratio of 50:3:1, respectively.4 Bladder
cancer occurs mainly in older people, with 90 percent of patients
aged 55 or older.5 With more than 81,000 new cases expected to be
diagnosed in 2020, bladder cancer accounts for about five percent
of all new cases of cancer in the U.S. each year.6 It is the fourth
most common cancer in men.7
About CRPC
According to the American Cancer Society, in 2020, approximately
192,000 new cases of prostate cancer will be diagnosed and 33,000
people will die from the disease.7 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.8 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.9,10,11
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 NSCLC, metastatic CRPC and UC
cohorts of the COSMIC-021 trial will be presented at ASCO20; the
potential synergistic effects with cabozantinib and immune
checkpoint inhibitors; Exelixis’ plans to initiate phase 3 pivotal
trials in advanced or metastatic NSCLC and CRPC; 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; 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 continuing
COVID-19 pandemic and its impact on Exelixis’ research and
development operations, including Exelixis’ ability to initiate new
clinical trials and clinical trial sites, enroll clinical trial
patients, conduct trials per protocol, and conduct drug research
and discovery operations and related activities; the availability
of data at the referenced times; complexities and the
unpredictability of the regulatory review and approval processes in
the U.S. and elsewhere; Exelixis’ and Roche’s continuing 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 May 5,
2020, 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, except as required
by law.
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. About Lung Cancer.
https://www.cancer.org/content/dam/CRC/PDF/Public/8703.00.pdf.
Accessed May 2020.
2 American Society of Clinical Oncology. Cancer.Net. Lung Cancer
- Non-Small Cell: Statistics.
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics.
Accessed May 2020.
3 National Cancer Institute. SEER Stat Fact Sheets: Lung and
Bronchus Cancer. https://seer.cancer.gov/statfacts/html/lungb.html.
Accessed May 2020.
4 Hurwitz, M. et al. Urothelial and Kidney Cancers. Cancer
Management.
http://www.cancernetwork.com/cancer-management/urothelial-and-kidney-cancers.
Accessed May 2020.
5 American Cancer Society. Bladder Cancer Key Statistics.
https://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-key-statistics.
Accessed May 2020.
6 National Cancer Institute. SEER Stat Fact Sheets: Bladder
Cancer. https://seer.cancer.gov/statfacts/html/urinb.html. Accessed
May 2020.
7 American Cancer Society: Cancer Facts & Figures 2020.
Available at:
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf.
Accessed May 2020.
8 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 May 2020.
9 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.
10 American Urological Association. Prostate Cancer: Castration
Resistant Guideline. 2018. Available at:
https://www.auanet.org/guidelines/prostate-cancer-castration-resistant-guideline.
Accessed May 2020.
11 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/20200513005815/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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