- First Presentation of Tucatinib With
Trastuzumab in Metastatic Colorectal Cancer -
- Findings Presented Today at the European
Society for Medical Oncology (ESMO) 2019 Congress -
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that
initial data were presented from the single arm phase 2 clinical
trial known as MOUNTAINEER. The trial is evaluating the
investigational agent tucatinib in combination with trastuzumab
(Herceptin®) in patients with HER2-positive (HER2+), RAS wild-type
metastatic colorectal cancer (mCRC) after treatment with first- and
second-line standard-of-care therapies. The regimen demonstrated
encouraging antitumor activity and was well tolerated.
Tucatinib is an oral, small molecule tyrosine kinase inhibitor
that is highly selective for HER2. HER2 amplification or
overexpression occurs in approximately three-to-five percent of all
patients with mCRC.1,2 The results were presented during a poster
discussion session today at the European Society for Medical
Oncology (ESMO) 2019 Congress in Barcelona, Spain (Abstract
#527PD).
Initial results from 23 patients evaluable for
clinical/radiographic response are below.
- Objective response rate (ORR) was 52.2 percent (95% Confidence
Interval [CI], 30.6-73.2) with a median duration of response of
10.4 months (95% CI, 6.0-NE)
- Median progression-free survival (PFS) was 8.1 months (95% CI,
3.8-NE)
- Median overall survival (OS) was 18.7 months (95% CI,
12.3-NE)
- The combination of tucatinib and trastuzumab was well
tolerated. The most common treatment-related adverse events were
Grade 1 in severity and included increased aspartate
aminotransferase (AST, 38.5 percent; all Grade 1) increased alanine
aminotransferase (ALT, 23.1 percent; all Grade 1), and diarrhea
(23.1 percent; one Grade 1, four Grade 2, one Grade 3). There were
no Grade 4 or 5 treatment-related adverse events.
“It’s exciting to see the initial results from the MOUNTAINEER
trial. Tucatinib is a potent and selective inhibitor of HER2, and
the combination of tucatinib and trastuzumab demonstrated
significant activity for heavily pre-treated patients with
HER2-positive metastatic colorectal cancer,” said John H.
Strickler, M.D., Duke University Medical Center.
“There is an unmet clinical need for new treatments for patients
with HER2-positive metastatic colorectal cancer,” said Roger
Dansey, M.D., Chief Medical Officer at Seattle Genetics. “The trial
demonstrated that tucatinib has the potential to play a role in the
treatment of colorectal cancer. We look forward to developing
tucatinib in combination with trastuzumab and other therapies for
the treatment of HER2-positive metastatic colorectal cancer.”
About MOUNTAINEER
MOUNTAINEER is a multi-center, open label, single-arm phase 2
clinical trial of tucatinib in combination with trastuzumab in
patients with HER2-positive, RAS wildtype metastatic or
unresectable colorectal cancer. The primary endpoint of the trial
is objective response rate by RECIST (Response Evaluation Criteria
in Solid Tumors) v1.1 criteria. Progression-free survival, duration
of response, overall survival and safety and tolerability of the
combination regimen are secondary objectives. Results for 26
patients were evaluated in this analysis, and enrollment is
ongoing. Three of the 26 patients who are on active treatment were
recently enrolled at the time of this analysis and had not yet
received first radiographic assessment of response.
MOUNTAINEER is a Seattle Genetics-sponsored multi-site clinical
trial initiated by the Academic and Community Cancer Research
United (ACCRU) Network. ACCRU is a non-profit cancer research
network comprised of more than 100 academic and community cancer
centers across the United States. Seattle Genetics is now
responsible for this ongoing clinical trial.
About Tucatinib
Tucatinib is an investigational, orally bioavailable, potent
tyrosine kinase inhibitor that is highly selective for HER2 without
significant inhibition of EGFR. Inhibition of EGFR has been
associated with significant 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.3,4 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, colorectal and gastric cancers.
HER2 mediates cell growth, differentiation and survival. Tumors
that overexpress HER2 are more aggressive and historically have
been associated with poor overall survival compared with
HER2-negative cancers. Tucatinib has been granted orphan drug
designation by the FDA for the treatment of HER2-positive
metastatic colorectal cancer and breast cancer patients with brain
metastases.
About Colorectal Cancer
Colorectal cancer is the second leading cause of cancer death in
the United States (U.S.).5 In 2019, it is estimated there will be
145,600 new cases and 51,020 deaths in the U.S.5 Approximately 21
percent of U.S. patients with colorectal cancer are diagnosed at
the advanced stage. 5 According to the U.S. Centers for Disease
Control and Prevention, the most effective way to reduce the risk
of colorectal cancer is routine screening beginning at age 50. In
colorectal cancer, human epidermal growth factor receptor 2 (HER2)
is overexpressed in three-to-five percent of patients.1,2 There are
currently no therapies approved that specifically target HER2 in
colorectal cancer.
About Seattle Genetics
Seattle Genetics, Inc. is an emerging multi-product, global
biotechnology company that develops and commercializes
transformative therapies targeting cancer to make a meaningful
difference in people’s lives. ADCETRIS® (brentuximab vedotin)
utilizes the company’s industry-leading antibody-drug conjugate
(ADC) technology and is currently approved for the treatment of
multiple CD30-expressing lymphomas. Beyond ADCETRIS, the company
has established a pipeline of novel targeted therapies at various
stages of clinical testing, including three in ongoing pivotal
trials for solid tumors. Enfortumab vedotin for metastatic
urothelial cancer and tisotumab vedotin for metastatic cervical
cancer utilize our proprietary ADC technology. Tucatinib, a small
molecule tyrosine kinase inhibitor, is in a pivotal trial for
HER2-positive metastatic breast cancer. In addition, we are
leveraging our expertise in empowered antibodies to build a
portfolio of proprietary immuno-oncology agents in clinical trials
targeting hematologic malignancies and solid tumors. The company is
headquartered in Bothell, Washington, and has a European office in
Switzerland. For more information on our robust pipeline, visit
www.seattlegenetics.com and follow @SeattleGenetics on Twitter.
Forward Looking Statements
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the possible
efficacy, safety and the therapeutic uses of tucatinib, and
anticipated clinical development activities including ongoing and
future clinical trials and potential regulatory actions. Actual
results or developments may differ materially from those projected
or implied in these forward-looking statements. Factors that may
cause such a difference include the difficulty and uncertainty of
pharmaceutical product development, including the risks that
Seattle Genetics may experience delays, setbacks or failures in its
clinical development programs due to potential lack of efficacy,
adverse events or adverse regulatory actions as tucatinib advances
in clinical trials even after promising results in earlier clinical
trials. More information about the risks and uncertainties faced by
Seattle Genetics is contained under the caption “Risk Factors”
included in the company’s Quarterly Report on Form 10-Q for the
quarter ended June 30, 2019 filed with the Securities and Exchange
Commission. Seattle Genetics disclaims any intention or obligation
to update or revise any forward-looking statements, whether as a
result of new information, future events or otherwise, except as
required by law.
References:
1.
Takegawa N and Yonesaka K (2017). HER2 as
an emerging oncotarget for colorectal cancer treatment after
failure of anti-epidermal growth factor receptor therapy. Clin
Colorectal Cancer 16: 247-51.
2.
Valtorta E., et al. Assessment of a HER2
scoring system for colorectal cancer: results from a validation
study. Mod Pathol 28: 1481-91 2015.
3.
Moulder S., et al. Phase I Study of
ONT-380, a HER2 Inhibitor, in Patients with HER2+-Advanced Solid
Tumors, with an Expansion Cohort in HER2+ Metastatic Breast Cancer
(MBC). Clin Cancer Res; 23(14) July 15, 2017.
4.
Murthy R., et al. Tucatinib with
capecitabine and trastuzumab in advanced HER2-positive metastatic
breast cancer with and without brain metastases: a non-randomized,
open-label, phase 1b study. Lancet Oncol 2018; 19: 880-88.
5.
SEER Cancer Stat Facts: Colorectal Cancer.
National Cancer Institute. Bethesda, MD.
https://seer.cancer.gov/statfacts/html/colorect.html. Accessed
September 17, 2019.
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version on businesswire.com: https://www.businesswire.com/news/home/20190929005010/en/
Media: Monique Greer (425) 527-4641 mgreer@seagen.com
Investors: Peggy Pinkston (425) 527-4160
ppinkston@seagen.com
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