– Submission Based on Positive Pivotal
HER2CLIMB Trial Results Recently Presented at the 2019 San Antonio
Breast Cancer Symposium and Published in the New England Journal of
Medicine –
– FDA Granted Breakthrough Therapy Designation
for Tucatinib in Locally Advanced or Metastatic HER2-Positive
Breast Cancer –
– First Investigational Therapy in a Pivotal
Trial to Address Unmet Need for Patients with Metastatic
HER2-Positive Breast Cancer with or without Brain Metastases –
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced it has
completed the submission of a New Drug Application (NDA) to the
U.S. Food and Drug Administration (FDA) for tucatinib. This NDA
requests FDA approval of tucatinib in combination with trastuzumab
and capecitabine for treatment of patients with locally advanced
unresectable or metastatic HER2-positive breast cancer, including
patients with brain metastases, who have received at least three
prior HER2-directed agents separately or in combination, in the
neoadjuvant, adjuvant or metastatic setting. The submission is
based on the results of HER2CLIMB, a randomized pivotal trial
comparing tucatinib added to trastuzumab and capecitabine versus
trastuzumab and capecitabine alone. HER2CLIMB trial results were
presented on December 11, 2019 at the 2019 San Antonio Breast
Cancer Symposium and published in the New England Journal of
Medicine. Tucatinib is an oral, small molecule tyrosine kinase
inhibitor (TKI) that is highly selective for HER2.
Tucatinib was recently granted Breakthrough Therapy designation
by the FDA in combination with trastuzumab and capecitabine, for
treatment of patients with locally advanced unresectable or
metastatic HER2-positive breast cancer, including patients with
brain metastases, who have been treated with trastuzumab,
pertuzumab, and T-DM1. This designation was based on data from the
HER2CLIMB trial.
“Today’s submission marks another important milestone for
Seattle Genetics and tucatinib, and a potential advance for
patients with either locally advanced or metastatic HER2-positive
breast cancer, including those with and without brain metastases,”
said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics.
“We look forward to working with the FDA on the review of this
application.”
About HER2-Positive Breast Cancer
Patients with HER2-positive 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. An
estimated 271,270 new cases of invasive breast cancer will be
diagnosed in the U.S. in 2019.1 Between 15 and 20 percent of breast
cancer cases worldwide are HER2-positive.2 Historically,
HER2-positive breast cancer tends to be more aggressive and more
likely to recur than HER2-negative breast cancer.2, 3, 4 In
patients with metastatic breast cancer, the most common site of
first metastasis is in bone, followed by lung, brain, and liver.5,
6 Up to 50 percent of metastatic HER2-positive breast cancer
patients develop brain metastases over time.2, 7 Despite recent
treatment advances, there is still a significant need for new
therapies that can impact metastatic disease, especially brain
metastases. There are currently no approved therapies demonstrating
progression-free survival or overall survival benefit for the
treatment of patients with HER2-positive metastatic breast cancer
after progression on T-DM1.8, 9, 10
About HER2CLIMB
HER2CLIMB is a multinational randomized (2:1), double-blind,
placebo-controlled, active comparator, pivotal clinical trial
comparing tucatinib in combination with trastuzumab and
capecitabine compared with trastuzumab and capecitabine alone in
patients with locally advanced unresectable or metastatic
HER2-positive breast cancer who were previously treated with
trastuzumab, pertuzumab, and T-DM1. The primary endpoint of the
trial was PFS per Response Evaluation Criteria in Solid Tumors
(RECIST) v1.1 as determined by blinded independent central review
(BICR) in the first 480 patients enrolled in the trial. HER2CLIMB
enrolled a total of 612 patients to support the analyses of key
secondary endpoints, including overall survival, PFS per BICR in
patients with brain metastases at baseline, and confirmed objective
response rate. Safety data were evaluated throughout the study.
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 targeted 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, colorectal, and gastric cancers. HER2
mediates cell growth, differentiation, and survival. Tucatinib has
been granted orphan drug designation by the FDA for the treatment
of breast cancer patients with brain metastases.
In addition to HER2CLIMB, tucatinib is being evaluated in a
randomized, double-blind, placebo-controlled, multi-center phase 3
trial of tucatinib in combination with T-DM1 compared to T-DM1
alone, in patients with unresectable locally advanced or metastatic
HER2-positive breast cancer, including those with brain metastases,
who have had prior treatment with a taxane and trastuzumab. The
primary endpoint is progression-free survival per RECIST criteria.
Secondary endpoints include overall survival, objective response
rate, and duration of response. The trial is being conducted in
North America and is expected to enroll approximately 460 patients.
More information about the phase 3 trial, including enrolling
centers, is available at www.clinicaltrials.gov.
Tucatinib is also being evaluated in a multi-center, open-label,
single-arm phase 2 clinical trial known as MOUNTAINEER, which is
evaluating 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 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 an analysis and presented at the
European Society for Medical Oncology (ESMO) 2019 Congress.
Enrollment is ongoing. More information about the MOUNTAINEER
trial, including enrolling centers, is available at
www.clinicaltrials.gov.
About Seattle Genetics
Seattle Genetics, Inc. is a global biotechnology company that
discovers, develops, and commercializes transformative medicines
targeting cancer to make a meaningful difference in people’s lives.
ADCETRIS® (brentuximab vedotin) and PADCEV™ (enfortumab
vedotin-ejfv) use the company’s industry-leading antibody-drug
conjugate (ADC) technology designed to bring a powerful medicine
directly to cancer cells. ADCETRIS is approved for the treatment of
several types of CD30-expressing lymphomas, and PADCEV is approved
to treat adults with metastatic urothelial cancer. In addition,
investigational agent tucatinib, a small molecule tyrosine kinase
inhibitor, is in late-stage development for HER2-positive
metastatic breast cancer, and in clinical development for
metastatic colorectal cancer. The company is headquartered in
Bothell, Washington, and has offices in California, Switzerland,
and the European Union. 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 potential FDA
approval of tucatinib in combination with trastuzumab and
capecitabine for treatment of patients with locally advanced
unresectable or metastatic HER2-positive breast cancer, including
patients with brain metastases, who have received at least three
prior HER2-directed agents separately or in combination, in the
neoadjuvant, adjuvant or metastatic setting; the therapeutic
potential of tucatinib, including its possible efficacy, safety and
therapeutic uses and anticipated development activities including
ongoing and future clinical trials. 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 possibility that the New Drug Application
submission based on the HER2CLIMB trial may not be accepted for
filing by, or ultimately approved by, the FDA in a timely manner or
at all or with the requested label; the difficulty and uncertainty
of pharmaceutical product development; the risk of adverse events
or safety signals; and the possibility of disappointing results in
ongoing or future clinical trials despite earlier promising
clinical results. 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 September 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:
- American Cancer Society, Cancer Facts and Figures
2018-2019.
- Loibl S, Gianni L (2017). HER2-positive breast cancer. The
Lancet 389(10087): 2415-29.
- Slamon D, Clark G, Wong S, et al. (1987). Human breast cancer:
correlation of relapse and survival with amplification of the
HER-2/neu oncogene. Science 235(4785): 177-82.
- American Cancer Society (ACS) (2018). Breast cancer HER2
status. Accessed: December 10, 2018.
- Kennecke H, Yerushalmi R, Woods R, et al. (2010). Metastatic
Behavior of Breast Cancer Subtypes. Journal of Clinical Oncology
28(20): 3271-7.
- Berman AT, Thukral AD, Hwang W-T, et al. (2013). Incidence and
Patterns of Distant Metastases for Patients With Early-Stage Breast
Cancer After Breast Conservation Treatment. Clinical Breast Cancer
13(2): 88-94.
- Duchnowska R, Loibl S, Jassem J (2018). Tyrosine kinase
inhibitors for brain metastases in HER2-positive breast cancer.
Cancer Treatment Reviews 67: 71-7.
- Verma S, Miles D, Gianni L, et al. (2012). Trastuzumab
Emtansine for HER2-Positive Advanced Breast Cancer. New England
Journal of Medicine 367(19): 1783-91.
- Geyer CE, Forster J, Lindquist D, et al. (2006). Lapatinib plus
Capecitabine for HER2-Positive Advanced Breast Cancer. New England
Journal of Medicine 355(26): 2733-43.
- Blackwell KL, Burstein HJ, Storniolo AM, et al. (2012). Overall
Survival Benefit With Lapatinib in Combination With Trastuzumab for
Patients With Human Epidermal Growth Factor Receptor 2–Positive
Metastatic Breast Cancer: Final Results From the EGF104900 Study.
Journal of Clinical Oncology 30(21): 2585-92.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20191223005127/en/
Media: Monique Greer (425) 527-4641 mgreer@seagen.com
Investors: Peggy Pinkston (425) 527-4160
ppinkston@seagen.com
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