Results from Pooled Analysis Support the
Potential Utility of Tucatinib for Patients with HER2+ Metastatic
Breast Cancer with Brain Metastases
Cascadian Therapeutics, Inc. (NASDAQ:CASC),
a clinical-stage biopharmaceutical company, today announced
tucatinib data in multiple tumor types were presented at the
European Society for Medical Oncology (ESMO) 2017 Congress being
held September 8-12, 2017 in Madrid, Spain. Results from the pooled
analysis of Phase 1b combination studies support the potential
utility of tucatinib for patients with HER2-positive (HER2+)
metastatic breast cancer with brain metastases, including untreated
or progressive brain metastases after radiation therapy. HER2
disease has been associated with shorter survival times as well as
a higher risk of recurrence and brain metastases.
“Approximately 30-to-50 percent of patients with metastatic
HER2+ breast cancer will develop brain metastases over time and,
historically, patients with HER2+ brain metastases have had poorer
outcomes compared to those without,” said Stacy L. Moulder, MD,
Associate Professor, Department of Breast Medical Oncology, The
University of Texas MD Anderson Cancer Center, Houston, TX. “The
results from this pooled analysis of tucatinib combination studies
suggesting that patients with HER2+ brain metastases, including
those with untreated or progressing disease, have similar
progression-free survival compared to those without brain
metastases is promising and supports inclusion of patients with
brain metastases into ongoing clinical trials. There remains a
clinical need for safe and effective HER2-targeted therapies that
are active both systemically and in the brain.”
Luke Walker, MD, Senior Vice President, Clinical Development of
Cascadian Therapeutics, added, “These data from our Phase 1b trials
further support the inclusion of patients with brain metastases in
our ongoing registrational trial of tucatinib in combination with
capecitabine and trastuzumab. This trial, known as HER2CLIMB, is
enrolling patients with all types of brain metastases, including
untreated, previously treated or progressing brain metastases.
Approximately half of patients enrolled in HER2CLIMB to date have
had brain metastases at study entry, which will allow us to assess
activity in that subpopulation in a statistically meaningful
way."
Progression-free survival (PFS) and site of first
progression in HER2+ metastatic breast cancer patients with or
without brain metastases: A pooled analysis of tucatinib phase I
studies (Poster 264)
In this poster (264), data from two Phase 1b combination studies
of tucatinib were pooled to analyze baseline characteristics and
outcomes of patients with and without brain metastases: tucatinib
in combination with trastuzumab (Herceptin®) and capecitabine
(Xeloda®) in heavily pre-treated patients with advanced HER2+
breast cancer with or without brain metastases (ONT-380-005/Triplet
study), and tucatinib in combination with T-DM1 (ONT-380-004). Of
the 77 patients in the pooled analysis, 47 percent (n=36) of
patients are without brain metastases and 53 percent (n=41) with
brain metastases, including patients with untreated or progressive
brain metastases after radiation therapy. Four subgroups were
identified retrospectively based on historical data and then
compared with respect to baseline characteristics, progression-free
survival and site of progression. Data from pooled tucatinib
studies suggest the PFS of patients with and without brain
metastases were similar, regardless of whether brain metastases
were untreated or progressed after radiation therapy.
In addition, the following nonclinical poster supports the
clinical evaluation of tucatinib for the treatment of other HER2+
tumor types. Tucatinib, a HER2 selective kinase inhibitor,
is active in patient derived xenograft (PDX) models of
HER2-amplified colorectal, esophageal and gastric cancer (Poster
1639)
In this poster, data are presented that show tucatinib is active
as a single agent in nonclinical models of HER2+ gastrointestinal
cancers, including colorectal, esophageal and gastric cancers. The
data also demonstrate that tucatinib combined with trastuzumab
displayed superior anti-tumor activity compared with either single
agent, producing a higher proportion of partial and complete tumor
regressions. These nonclinical data support the clinical evaluation
of tucatinib for the treatment of HER2+ gastrointestinal cancers.
Tucatinib is currently being evaluated in an open label Phase 2
study combining tucatinib with trastuzumab in HER2+/RAS wild type
metastatic colorectal cancer (MOUNTAINEER: NCT03043313).
Scott Peterson, Ph.D., Chief Scientific Officer of Cascadian
Therapeutics, commented, “We are pleased to share this update
regarding the potential versatility of tucatinib in combination for
other tumor types beyond breast cancer.” To access these poster
presentations, please visit www.cascadianrx.com.About
Tucatinib
Tucatinib is an investigational, orally bioavailable, potent
tyrosine kinase inhibitor that is highly selective for HER2 without
inhibition of EGFR. Inhibition of EGFR has been associated with
clinical toxicities, including skin rash and diarrhea. Tucatinib
has shown activity as a single agent and in combination with both
chemotherapy and other HER2 directed agents such as trastuzumab.1,2
Studies of tucatinib in these combinations have shown activity both
systemically and in brain metastases. HER2 is a growth factor
receptor that is overexpressed in multiple cancers, including
breast, ovarian and gastric cancers. HER2 mediates cell growth,
differentiation and survival. Tumors that overexpress HER2 (HER2+)
are more aggressive and historically have been associated with poor
overall survival, compared with HER2-negative cancers.
About HER2CLIMB Pivotal Trial
HER2CLIMB is a randomized (2:1), double-blind,
placebo-controlled pivotal clinical trial comparing tucatinib vs.
placebo, each in combination with capecitabine and trastuzumab and
without loperamide or budesonide prophylaxis, in patients with
locally advanced or metastatic HER2+ breast cancer who have had
prior treatment with trastuzumab, pertuzumab and ado-trastuzumab
emtansine, also known as T-DM1. The primary endpoint is
progression-free survival (PFS) based upon independent radiologic
review. Key objectives related to assessing activity in brain
metastases include a key secondary endpoint of PFS in a subset of
patients with brain metastases. All patients will be followed for
overall survival. HER2CLIMB is currently enrolling patients in the
United States, Canada, Western Europe and Australia. Additional
information is available at www.HER2CLIMB.com.
About HER2+ Metastatic Breast Cancer
Patients with HER2+ breast cancer have tumors with high levels
of a protein called human epidermal growth factor receptor 2
(HER2), which promotes the aggressive spread of cancer cells. The
American Cancer Society estimates that 20-25 percent of the
approximately 246,660 annual new cases of breast cancer diagnoses
in the U.S. are HER2+. Historically, HER2 disease has been
associated with shorter survival times as well as a higher risk of
recurrence and CNS disease (brain metastases). Up to 50 percent of
patients with HER2+ metastatic breast cancer experience brain
metastases over time.3 Over the past two decades, the
approvals of four targeted treatments (trastuzumab, pertuzumab,
lapatinib, and T-DM1) have led to improved time to
progression and survival rates of patients with HER2+ breast
cancer. Despite these advances, there is still a significant need
for new therapies that can impact metastatic disease, including
brain metastases, and be tolerated for longer periods of time.
About Cascadian Therapeutics
Cascadian Therapeutics is a clinical-stage biopharmaceutical
company dedicated to developing innovative product candidates for
the treatment of cancer. Its lead product candidate, tucatinib, is
an investigational oral, selective small molecule HER2 inhibitor.
Cascadian Therapeutics is conducting a randomized, double-blind,
controlled pivotal clinical trial called HER2CLIMB, which is
comparing tucatinib vs. placebo, each in combination with
capecitabine and trastuzumab, in patients with locally advanced or
metastatic HER2+ breast cancer with and without brain metastases,
who have previously been treated with trastuzumab, pertuzumab and
T-DM1. Additional details on HER2CLIMB can be found at
www.HER2CLIMB.com or www.clinicaltrials.gov. For more information,
please visit www.cascadianrx.com.Forward-Looking
Statements In order to provide Cascadian Therapeutics'
investors with an understanding of its current results and future
prospects, this release contains statements that are
forward-looking. Any statements contained in this press release
that are not statements of historical fact may be deemed to be
forward-looking statements. Words such as "believes,"
"anticipates," "plans," "expects," "will," "intends," "potential,"
"possible" and similar expressions are intended to identify
forward-looking statements. These forward-looking statements
include Cascadian Therapeutics' expectations regarding clinical
development activities, HER2CLIMB enrollment, and the potential
benefits of its product candidates. Forward-looking statements
involve risks and uncertainties related to Cascadian Therapeutics'
business and the general economic environment, many of which are
beyond its control. These risks, uncertainties and other factors
could cause Cascadian Therapeutics' actual results to differ
materially from those projected in forward-looking statements,
including the risks associated with the costs and expenses of
developing its product candidates, the adequacy of financing and
cash, cash equivalents and investments, changes in general
accounting policies, general economic factors, achievement of the
results it anticipates from its preclinical development and
clinical trials of its product candidates, the receipt of
regulatory approvals, and its ability to adequately obtain and
protect its intellectual property rights. Although Cascadian
Therapeutics believes that the forward-looking statements contained
herein are reasonable as of the date hereof, it can give no
assurance that its expectations are correct. All forward-looking
statements are expressly qualified in their entirety by this
cautionary statement. For a detailed description of Cascadian
Therapeutics' risks and uncertainties, you should review the
documents filed by Cascadian Therapeutics with the securities
regulators in the United States on EDGAR and in Canada on SEDAR.
Cascadian Therapeutics does not undertake any obligation to
publicly update its forward-looking statements based on events or
circumstances after the date hereof, except to the extent required
by law.
1 Moulder, S. et al., Phase 1 Study of ONT-380, a HER2
Inhibitor, in Patients with HER2+ Advanced Solid Tumors, with an
Expansion Cohort in HER2+ Metastatic Breast Cancer. Clin
Cancer Res. May 2017. 2 Hamilton, E. et al., Efficacy of
a Phase 1b Study of Tucatinib (ONT-380), an Oral HER2-Specific
Inhibitor, in Combination with Capecitabine and Trastuzumab in
HER2+ Metastatic Breast Cancer, Including Patients with Brain
Metastases. Presented at the SABCS Annual Meeting 2016. December 9,
2016 (Poster P4-21-01). 3 Ramakrishna N., et al., Journal of
Clinical Oncology. 32, no. 19 (July 2014) 2100-2108.All trademarks
used or mentioned in this press release are protected by law.
Herceptin and Xeloda are registered trademarks of Genentech,
Inc.
Investor and Media Contact:Monique
GreerCascadian Therapeutics206-801-2107mgreer@cascadianrx.com
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