Exelixis Announces Further Expansion to Clinical Research Protocol for Phase 1b COSMIC-021 Trial of Cabozantinib …


SOUTH SAN FRANCISCO, Calif.–()–Exelixis,
Inc.
(Nasdaq:EXEL) today announced an amendment to the protocol for
COSMIC-021, the phase 1b trial of cabozantinib (CABOMETYX®)
in combination with atezolizumab (TECENTRIQ®) in patients
with locally advanced or metastatic solid tumors to add 10 new expansion
cohorts to the trial. The primary objective in the expansion stage of
this trial remains to determine the objective response rate in each
cohort.

The 10 new expansion cohorts will evaluate the combination of
cabozantinib and atezolizumab in patients with:

  • non-small cell lung cancer (NSCLC) with an EGFR mutation who have
    progressed following treatment with an EGFR-targeting tyrosine kinase
    inhibitor for metastatic disease
  • renal cell carcinoma (RCC) with non-clear cell histology who have not
    had prior systemic anticancer therapy for inoperable, locally
    advanced, recurrent or metastatic disease
  • triple-negative breast cancer who have progressed following treatment
    with at least one prior systemic therapy for inoperable, locally
    advanced, recurrent or metastatic disease
  • epithelial ovarian cancer who have platinum-resistant or refractory
    disease
  • endometrial cancer who have progressed following treatment with at
    least one prior systemic therapy for inoperable, locally advanced,
    recurrent or metastatic disease
  • advanced hepatocellular carcinoma (HCC) who have a Child-Pugh score of
    A and have not had prior systemic anticancer therapy for inoperable,
    locally advanced, recurrent or metastatic disease
  • gastric or gastroesophageal junction adenocarcinoma who have
    progressed following treatment with platinum-containing or
    fluoropyrimidine-containing chemotherapy for inoperable locally
    advanced, recurrent or metastatic disease
  • colorectal adenocarcinoma who have progressed following treatment with
    systemic chemotherapy that contained fluoropyrimidine in combination
    with oxaliplatin or irinotecan for metastatic disease
  • head and neck cancer of squamous cell histology who have progressed
    following treatment with platinum-containing chemotherapy for
    inoperable locally advanced, recurrent or metastatic disease
  • differentiated thyroid cancer who are radio-refractory or deemed
    ineligible for treatment with iodine-131

“We look forward to expanding this phase 1b COSMIC-021 clinical trial of
cabozantinib in combination with atezolizumab in a number of additional
tumor types, which include patient populations in significant need of
new therapies that may improve response rates, slow disease progression
and improve treatment outcomes,” said Gisela Schwab, M.D., President,
Product Development and Medical Affairs and Chief Medical Officer,
Exelixis. “We look forward to advancing this trial and to generating
data that will inform late stage trials of cabozantinib in combination
with immune checkpoint inhibitors.”

In January 2018, the protocol was amended to include the following eight
expansion cohorts, which are actively enrolling patients with:

  • RCC with clear cell histology who have not had prior systemic
    anticancer therapy
  • urothelial carcinoma (UC) who have progressed on or after
    platinum-containing chemotherapy
  • UC who are ineligible for cisplatin-based chemotherapy and have not
    received prior systemic chemotherapy for inoperable, locally advanced
    or metastatic disease
  • UC who are eligible for cisplatin-based chemotherapy and have not
    received prior systemic chemotherapy for inoperable, locally advanced
    or metastatic disease
  • advanced non-squamous NSCLC without a defined tumor genetic alteration
    (EGFR, ALK, ROS1, or BRAF) who have not received prior therapy with an
    immune checkpoint inhibitor
  • NSCLC without a defined tumor genetic alteration who have progressed
    following treatment with an immune checkpoint inhibitor
  • UC who have progressed following treatment with an immune checkpoint
    inhibitor
  • castration-resistant prostate cancer (CRPC) who have previously
    received enzalutamide and/or abiraterone acetate and experienced
    radiographic disease progression in soft tissue

The dose-escalation phase of the study determined the optimal dose of
cabozantinib as 40 mg daily when given in combination with atezolizumab
(1200 mg infusion once every 3 weeks). Each expansion cohort of this
multicenter phase 1b, open-label study will initially enroll
approximately 30 patients. Up to 80 may enroll in the cohorts of
patients with UC or NSCLC who have been previously treated with an
immune checkpoint inhibitor, with up to a total of 640 patients in the
entire study.

More information about the currently enrolling cohorts in this trial is
available at ClinicalTrials.gov.

TECENTRIQ® (atezolizumab) is a registered trademark of
Genentech, a member of the Roche Group.

About Exelixis’ Collaboration with Ipsen

On February 29, 2016, Exelixis and Ipsen jointly announced an exclusive
licensing agreement for the commercialization and further development of
cabozantinib indications outside of the United States, Canada and Japan.
On December 21, 2016, this agreement was amended to include
commercialization rights for Ipsen in Canada. Ipsen has opted to
participate in the funding of the previously announced COSMIC-021 phase
1b trial cohorts in patients with locally advanced or metastatic UC,
RCC, CRPC and NSCLC. They may also participate in these expansion trial
cohorts and in future studies at their choosing and, in such cases,
would have access to the results to support potential future regulatory
submissions.

About Exelixis’ Collaboration with Takeda

On January 30, 2017, Exelixis and Takeda jointly announced an exclusive
licensing agreement for the commercialization and further development of
cabozantinib indications in Japan. Under the parties’ collaboration
agreement, if Takeda opts to participate in funding the COSMIC-021 phase
1b trial, or future studies, Takeda will have access to the respective
study results to support potential future regulatory submissions in
their territory.

Exelixis holds the exclusive rights to develop and commercialize
cabozantinib in the United States.

About CABOMETYX® (cabozantinib)

CABOMETYX tablets are approved in the United States for the treatment of
patients with advanced RCC. CABOMETYX tablets are also approved in the
European Union, Norway, Iceland, Australia, Switzerland and South Korea
for the treatment of advanced RCC in adults who have received prior
VEGF-targeted therapy, and in the European Union for previously
untreated intermediate- or poor-risk advanced RCC. On May 29, 2018,
Exelixis announced that the U.S. Food and Drug Administration (FDA)
accepted for filing the company’s supplemental New Drug Application
(sNDA) for CABOMETYX tablets as a treatment for patients with previously
treated advanced HCC. On March 28, 2018, Ipsen announced that the
European Medicines Agency validated its application for a new indication
for cabozantinib as a treatment for previously treated advanced HCC in
the European Union.

Please see Important Safety Information below and full U.S. prescribing
information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.

U.S. Important Safety Information

  • Hemorrhage: Severe and fatal hemorrhages have occurred with
    CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic
    events was 3% in CABOMETYX-treated patients. Do not administer
    CABOMETYX to patients that have or are at risk for severe hemorrhage.
  • Gastrointestinal (GI) Perforations and Fistulas: In RCC
    studies, fistulas were reported in 1% of CABOMETYX-treated patients.
    Fatal perforations occurred in patients treated with CABOMETYX. In RCC
    studies, gastrointestinal (GI) perforations were reported in 1% of
    CABOMETYX-treated patients. Monitor patients for symptoms of fistulas
    and perforations, including abscess and sepsis. Discontinue CABOMETYX
    in patients who experience a fistula which cannot be appropriately
    managed or a GI perforation.
  • Thrombotic Events: CABOMETYX treatment results in an increased
    incidence of thrombotic events. In RCC studies, venous thromboembolism
    occurred in 9% (including 5% pulmonary embolism) and arterial
    thromboembolism occurred in 1% of CABOMETYX-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,
    including hypertensive crisis. In RCC studies, hypertension was
    reported in 44% (18% Grade ≥ 3) of CABOMETYX-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: In RCC studies, diarrhea occurred in 74% of patients
    treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients
    treated with CABOMETYX. 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.
  • Palmar-Plantar Erythrodysesthesia (PPE): In RCC studies,
    palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients
    treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated
    with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable
    Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume
    CABOMETYX at a reduced dose.
  • Reversible Posterior Leukoencephalopathy Syndrome (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 may be associated with CABOMETYX. Advise
    pregnant women of the potential risk to a fetus. Advise females of
    reproductive potential to use effective contraception during CABOMETYX
    treatment and for 4 months after the last dose.
  • Adverse Reactions: The most commonly reported (≥25%) adverse
    reactions are: diarrhea, fatigue, nausea, decreased appetite,
    hypertension, PPE, weight decreased, vomiting, dysgeusia, and
    stomatitis.
  • Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4
    inhibitors cannot be avoided, reduce the CABOMETYX dosage.
  • Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4
    inducers cannot be avoided, increase the CABOMETYX dosage.
  • Lactation: Advise women not to breastfeed while taking
    CABOMETYX and for 4 months after the final dose.
  • Hepatic Impairment: In patients with mild to 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
genetic systems, 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. We discovered our lead
compounds, cabozantinib and cobimetinib, and advanced them into clinical
development before entering into partnerships with leading
biopharmaceutical companies in our efforts to bring these medicines to
patients globally. We are steadfast in our commitment to prudently
reinvest in our business to maximize the potential of our pipeline. We
intend to supplement 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 recently earned a spot on
Deloitte’s Technology Fast 500 list, a yearly award program honoring the
500 fastest-growing companies over the past four years. For more
information about Exelixis, please visit www.exelixis.com,
follow @ExelixisInc
on Twitter or like Exelixis,
Inc.
on Facebook.

Exelixis Forward-Looking Statement Disclaimer

This press release contains forward-looking statements, including,
without limitation, statements related to: the clinical and therapeutic
potential of cabozantinib in combination with atezolizumab in patients
with locally advanced or metastatic solid tumors; the potential for
COSMIC-021 to generate data that will inform late stage trials of
cabozantinib in combination with immune checkpoint inhibitors; the
potential for Ipsen’s and Takeda’s participation in future cabozantinib
studies under their respective collaborations and to have access to the
results to support potential future regulatory submissions in their
territories; Exelixis’ commitment to reinvesting in its business to
maximize the potential of its pipeline, including supplementing its
existing therapeutic assets through targeted business development
activities and internal drug discovery; and Exelixis’ mission to deliver
the next generation of Exelixis medicines and help patients recover
stronger and live longer. Words such as “look forward,” “may,” “will,”
“commitment,” “potential,” “intend,” or other similar expressions
identify forward-looking statements, but the absence of these words does
not necessarily mean that a statement is not forward-looking. In
addition, any statements that refer to expectations, projections or
other characterizations of future events or circumstances are
forward-looking statements. These forward-looking statements 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: Exelixis’ ability and the ability of its collaborators to
conduct clinical trials of cabozantinib and cobimetinib both alone and
in combination with other therapies sufficient to achieve a positive
completion; risks related to the potential failure of cabozantinib and
cobimetinib both alone and in combination with other therapies, to
demonstrate safety and efficacy in clinical testing; risks and
uncertainties related to regulatory review and approval processes and
Exelixis’ compliance with applicable legal and regulatory requirements;
the level of costs associated with Exelixis’ commercialization, research
and development and other activities; competition in the area of
business development activities and the inherent uncertainty of the drug
discovery process; Exelixis’ dependence on its relationships with its
cabozantinib collaboration partners, including, the level of their
investment in the resources necessary to successfully commercialize
partnered products in the territories where they are approved; market
acceptance of CABOMETYX, COMETRIQ, and COTELLIC and the availability of
coverage and reimbursement for these products; Exelixis’ dependence on
third-party vendors for the development, manufacture and supply of its
products; Exelixis’ ability to protect the company’s intellectual
property rights; market competition, including the potential for
competitors to obtain approval for generic versions of Exelixis’
marketed products; changes in economic and business conditions, and
other factors discussed under the caption “Risk Factors” in Exelixis’
quarterly report on Form 10-Q filed with the Securities and Exchange
Commission (SEC) on May 2, 2018, and in Exelixis’ future filings with
the SEC. The forward-looking statements made in this press release speak
only as of the date of this press release. Exelixis expressly disclaims
any duty, obligation or undertaking to release publicly any updates or
revisions to any forward-looking statements contained herein to reflect
any change in Exelixis’ expectations with regard thereto or any change
in events, conditions or circumstances on which any such statements are
based.

Exelixis, the Exelixis logo and CABOMETYX are registered U.S.
trademarks.



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