Cascadian Therapeutics, Inc. (NASDAQ:CASC), a clinical-stage
biopharmaceutical company, today announced that tucatinib in
combination with standard of care agents demonstrated prolonged
progression-free survival (PFS) in a subgroup of patients
participating in two ongoing Phase 1b studies. Results from a
subgroup analysis from these tucatinib combination studies showed
22 percent of patients with HER2-positive (HER2+) metastatic breast
cancer with and without brain metastases achieved prolonged PFS
defined as twice the median PFS seen in these studies or else
defined as survival greater than 17 months. Patients received a
median of two prior HER2-based regimens and the median duration of
the last prior treatment in this subgroup was 9.03 months. Patients
with prolonged PFS on tucatinib combination therapy included those
with characteristics that historically predict poor outcome such as
hormone receptor status, presence of visceral disease, burden of
systemic or brain disease and age. Results from this analysis will
be presented in a poster session at the 2017 San Antonio Breast
Cancer Symposium (SABCS) on Friday, December 8, 2017 beginning at
5:00 p.m. CST.
“One of the challenges in the treatment of HER2+ breast cancer
is the frequent development of brain metastases, which occur in up
to 50 percent of patients with advanced disease,” said Erika
Hamilton, M.D., Director of Breast and Gynecology Cancer Research
and Principal Investigator at Sarah Cannon Research Institute.
“Tucatinib in combination has shown early signs of activity in
HER2+ brain metastases. An active agent showing prolonged activity
systemically as well as in the brain, with a tolerable safety
profile, would represent a meaningful advancement in treating
metastatic breast cancer.”
Dr. Hamilton continued, “The more mature dataset from these
Phase 1b combination studies show tucatinib may be combined with
other standard targeted therapies to achieve disease control in
patients who have received multiple prior lines of therapy.”
Prolonged Progression-Free Survival in Advanced HER2+
Metastatic Breast Cancer with or without Brain Metastases: A
Pooled Analysis of Tucatinib Phase 1b Studies
In this poster, data from two Phase 1b combination studies of
tucatinib were pooled to analyze the subgroup of patients with
prolonged PFS, which was identified as patients achieving at least
twice the observed median PFS in the overall group. Baseline
characteristics and radiology findings were compared between the
subgroup of patients with or without prolonged PFS from two
studies: 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; n=27), and tucatinib in combination
with T-DM1 (ONT-380-004; n=50). Of the 77 patients in the pooled
analysis, 47 percent (n=36) of patients are without brain
metastases and 53 percent (n=41) are with brain metastases,
including patients with untreated or progressive brain metastases
after radiation therapy. Twenty-two percent (17/77) of patients
demonstrated prolonged PFS; 20 percent (n=10/50) from Study 004 and
26 percent (n=7/27) from Study 005/Triplet. Data from pooled
tucatinib studies suggest a similar proportion of patients with
brain metastases in the subgroup of patients with prolonged PFS
compared to the overall patient population.
In addition, the following investigator-initiated trial in
progress poster was presented at SABCS.
Phase 1b/2 Open-Label Single Arm Study to Evaluate
Safety and Efficacy of Tucatinib in Combination with Letrozole and
Palbociclib in Subjects with Hormone Receptor Positive and HER2
Positive Metastatic Breast Cancer (TULiP Trial)
The University of Colorado Cancer Center presented a trials in
progress poster summarizing the study design for the ongoing TULiP
trial in patients with hormone receptor positive and HER2-positive
(HR+/HER2+) metastatic breast cancer. In this study, tucatinib, a
highly selective inhibitor of HER2 tyrosine kinase, is combined
with an aromatase inhibitor letrozole and CDK4/6 inhibitor
palbociclib. The TULiP study is expecting to enroll 40 patients. It
is currently opened for enrollment at the University of Colorado
Denver, and soon will be opened at five additional academic
institutions (members of Academic Breast Cancer Research
Consortium): North Western University, Chicago, IL; University of
Texas Health and Science Center at San Antonio, TX; Stony Brook
University, NY; University of Arizona, Tucson, AZ, and University
of New Mexico, Albuquerque, NM. The Phase 1b part of the trial is
expected to enroll 20 patients and will evaluate the tolerability
of tucatinib given at maximum tolerated dose (300mg by mouth twice
a day) with the standard doses of palbociclib and letrozole. The
Phase 2 part of the trial is expected to enroll 20 additional
patients to enable analysis of efficacy by overall response rate
and progression-free survival. Because of documented activity of
tucatinib in the CNS disease, the TULiP trial will include patients
with brain metastases. For more information, visit
ClinicalTrials.gov, Identifier: NCT03054363.
“Finding novel treatments for HR+/HER2+ breast cancers remains
an area of unmet clinical need, because of intrinsic resistance of
these tumors to both anti-hormonal treatments and HER2-targeted
agents,” said Elena Shagisultanova, MD, PhD, Assistant Professor at
the University of Colorado Denver Cancer Center and Lead Principal
Investigator of TULiP trial. “We are very excited about the TULiP
trial. There is significant preclinical evidence on synergistic
anti-tumor activity of CDK4/6 inhibitors and HER2-targeted agents.
Tucatinib, palbociclib and letrozole have largely non-overlapping
toxicity profiles and metabolic pathways. We believe that this
triple combination of targeted agents will be well tolerated and
highly patient centered, as an effective non-chemotherapy based
regimen for treatment of patients with HR+/HER2+ metastatic breast
cancer. We are grateful for the support we received from both
Cascadian Therapeutics and Pfizer while working on this trial.”
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, and other
factors discussed under the caption “Risk Factors” in Cascadian
Therapeutics’ Quarterly Report on Form 10-Q for the quarterly
period ended September 30, 2017 filed with the Securities and
Exchange Commission. 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. Source: Cascadian Therapeutics, Inc.
Investor and Media Contact:Monique
GreerCascadian Therapeutics206-801-2107mgreer@cascadianrx.com
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