- FDA Action Date is August 20, 2020;
Application Under FDA’s Real-Time Oncology Review (RTOR) and Orbis
Pilot Programs -
- Supported by Results from Pivotal HER2CLIMB
Trial; First Investigational Therapy in a Pivotal Trial to Include
Patients with Metastatic HER2-Positive Breast Cancer with Active
Brain Metastases -
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that the
U.S. Food and Drug Administration (FDA) has accepted for priority
review the Company’s New Drug Application (NDA) for the
investigational medicine 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 filing 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 recently
presented at the 2019 San Antonio Breast Cancer Symposium and
published in the New England Journal of Medicine (NEJM). Under the
Prescription Drug User Fee Act (PDUFA), the FDA has set a target
action date of August 20, 2020. Tucatinib is an oral, small
molecule tyrosine kinase inhibitor (TKI) that is highly selective
for HER2.
“The FDA’s filing of the tucatinib NDA marks an important step
forward for patients with locally advanced or metastatic
HER2-positive breast cancer, including those with brain
metastases,” said Clay Siegall, Ph.D., President and Chief
Executive Officer of Seattle Genetics. “We are working
collaboratively with the FDA throughout the review process to bring
this important medicine to patients as quickly as possible.”
The NDA for tucatinib was submitted in December 2019 and is
being reviewed under the Real-Time Oncology Review (RTOR) Pilot
Program. The review of the tucatinib NDA is also being conducted
under Project Orbis, an initiative of the FDA Oncology Center of
Excellence. Project Orbis provides a framework for concurrent
submission and review of oncology drugs among participating
international partners. Tucatinib was recently granted Breakthrough
Therapy designation by the FDA in combination with trastuzumab and
capecitabine for the 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 pivotal HER2CLIMB trial.
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 growth 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 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 called HER2CLIMB-02. This trial is evaluating
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 (PFS) per RECIST
criteria. Secondary endpoints include overall survival, objective
response rate and duration of response. This global trial 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, with
tucatinib in combination with trastuzumab in patients with
HER2-positive, RAS wildtype metastatic or unresectable colorectal
cancer. The primary endpoint of the trial is overall response rate
by RECIST criteria. Duration of response, PFS, overall survival and
safety and tolerability of the combination regimen are secondary
objectives. Results for the first 26 patients were presented at the
European Society for Medical Oncology (ESMO) 2019 Congress.
Enrollment of up to 110 patients 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 PADCEVTM (enfortumab
vedotin-ejfv) use the company’s industry-leading antibody-drug
conjugate (ADC) technology. ADCETRIS is approved in certain
CD30-expressing lymphomas, and PADCEV is approved in certain
metastatic urothelial cancers. 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 potential approval
of tucatinib by regulatory authorities in Project Orbis countries
outside the U.S.; the timing of any such approvals; the therapeutic
potential of tucatinib, including its possible efficacy, safety and
therapeutic uses and 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 data from the HER2CLIMB trial may not be
sufficient to support approval of tucatinib in the U.S. or in other
Project Orbis countries; the possibility of delays in the
regulatory approval process; the possibility of other adverse
regulatory actions or developments; 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 Annual Report on
Form 10-K for the year ended December 31, 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20200213005275/en/
Media: Monique Greer (425) 527-4641 mgreer@seagen.com
Investors: Peggy Pinkston (425) 527-4160
ppinkston@seagen.com
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