- Application Supported by Results of Pivotal
HER2CLIMB Trial -
- First Investigational Therapy in a Pivotal
Trial to Include Patients with Metastatic HER2-Positive Breast
Cancer with Active Brain Metastases -
- EU Marketing Authorization Application (MAA)
Follows Recent Submission of Tucatinib New Drug Application (NDA)
to the U.S. Food and Drug Administration (FDA) -
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that the
European Medicines Agency (EMA) validated the Marketing
Authorization Application (MAA) for tucatinib, in combination with
trastuzumab and capecitabine, for the treatment of adult patients
with locally advanced unresectable or metastatic HER2-positive
breast cancer, including patients with brain metastases, who have
received at least two prior anti-HER2 treatment regimens. The EMA
validation of the MAA confirms that the submission is sufficiently
complete to begin the formal review process. Tucatinib is an oral,
small molecule tyrosine kinase inhibitor (TKI) that is highly
selective for HER2.
“Today, we achieved a significant milestone towards our goal of
making tucatinib available to patients with locally advanced
unresectable or metastatic HER2-positive breast cancer, including
those with brain metastases, around the world,” said Roger Dansey,
M.D., Chief Medical Officer at Seattle Genetics. “We look forward
to working with the EMA throughout the review process. If approved,
tucatinib has the potential to be a clinically meaningful advance
for patients in this disease setting.”
The MAA is based on data from the pivotal HER2CLIMB clinical
trial, which compared tucatinib in combination with trastuzumab and
capecitabine to trastuzumab and capecitabine alone in patients with
locally advanced unresectable or metastatic HER2-positive breast
cancer. Patients had previously received trastuzumab, pertuzumab
and T-DM1 (ado-trastuzumab emtansine). Patients had received a
median of four prior lines of therapy overall and three in the
metastatic setting. Forty-seven percent of the patients enrolled in
the trial had brain metastases at the time of enrollment. Results
of the pivotal HER2CLIMB trial were presented during an oral
presentation at the 2019 San Antonio Breast Cancer Symposium
(SABCS) and simultaneously published in the New England Journal of
Medicine (NEJM).
The New Drug Application (NDA) for tucatinib was submitted to
the U.S. Food and Drug Administration (FDA) on December 23, 2019
under the Real-Time Oncology Review 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
HER2CLIMB trial.
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 progression-free survival (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 (ORR). Safety data
were evaluated throughout the study.
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 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 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, 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 ORR by
RECIST criteria. PFS, 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 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 therapeutic
potential of tucatinib, including its possible efficacy, safety and
therapeutic uses; anticipated development activities including
ongoing and future clinical trials; and the potential to obtain
regulatory approvals of tucatinib in the United States, the
European Union and in countries participating in Project Orbis.
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, the risk of
adverse events or safety signals, the possibility of disappointing
results in ongoing or future clinical trials despite earlier
promising clinical results, the possibility that data from the
HER2CLIMB trial may not be sufficient to support approval of
tucatinib in the United States, the European Union or in other
countries participating in Project Orbis or that other adverse
regulatory actions could occur. 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:
1. American Cancer Society, Cancer Facts and Figures
2018-2019.
2. Loibl S, Gianni L (2017). HER2-positive breast cancer. The
Lancet 389(10087): 2415-29.
3. 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.
4. American Cancer Society (ACS) (2018). Breast cancer HER2
status. Accessed: December 10, 2018.
5. Kennecke H, Yerushalmi R, Woods R, et al. (2010). Metastatic
Behavior of Breast Cancer Subtypes. Journal of Clinical Oncology
28(20): 3271-7.
6. 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.
7. Duchnowska R, Loibl S, Jassem J (2018). Tyrosine kinase
inhibitors for brain metastases in HER2-positive breast cancer.
Cancer Treatment Reviews 67: 71-7.
8. 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.
9. 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.
10. 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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Media: Monique Greer (425) 527-4641 mgreer@seagen.com
Investors: Peggy Pinkston (425) 527-4160
ppinkston@seagen.com
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