Seattle Genetics Announces Initiation of Phase 3 Clinical Trial of Tucatinib in Combination with Ado-trastuzumab Emtansine (T...
October 10 2019 - 8:00AM
Business Wire
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced dosing of
the first patient in HER2CLIMB-02, a randomized phase 3 clinical
trial evaluating investigational agent tucatinib versus placebo, in
combination with standard-of-care ado-trastuzumab emtansine (T-DM1,
Kadcyla®), for patients with locally advanced or metastatic
HER2-positive (HER2+) breast cancer. This trial is intended to
support registration in the U.S. Tucatinib is an oral, small
molecule tyrosine kinase inhibitor that is highly selective for
HER2.
“We are building a comprehensive strategy for tucatinib in
combination with other medicines across a range of HER2-positive
cancers,” said Roger Dansey, M.D., Chief Medical Officer at Seattle
Genetics. “We are pleased to advance this tucatinib clinical trial
with the vision of improving combination outcomes for patients with
HER2-positive metastatic breast cancer who receive T-DM1. This
trial has the potential to support tucatinib use in earlier lines
of therapy.”
HER2CLIMB-02 is a multi-center, randomized, double-blind,
placebo-controlled phase 3 trial designed to evaluate tucatinib
versus placebo, in combination with T-DM1, in patients with
unresectable locally-advanced or metastatic HER2+ breast cancer,
including those with brain metastases, who have had prior treatment
with a taxane and trastuzumab in any setting. The primary endpoint
is progression-free survival per Response Evaluation Criteria in
Solid Tumors (RECIST). Secondary endpoints include overall
survival, objective response rate and duration of response. The
trial is expected to enroll approximately 460 patients. More
information about this phase 3 trial, including enrolling centers,
is available at www.clinicaltrials.gov.
HER2CLIMB-02 is based on the results from a completed phase 1b
study. The manuscript entitled “Tucatinib combined with
ado-trastuzumab emtansine in advanced ERBB2/HER2-positive
metastatic breast cancer: The results of a phase 1b trial”
evaluating tucatinib with the current standard of care
HER2-targeted antibody-drug conjugate, T-DM1, in previously treated
metastatic HER2-positive breast cancer was published in the July
2018 print edition of JAMA Oncology.
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.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 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 breast cancer patients with brain
metastases.
Tucatinib is being evaluated in an ongoing randomized,
double-blind, placebo-controlled pivotal trial called HER2CLIMB
comparing tucatinib vs. placebo, in combination with capecitabine
and trastuzumab in patients with pretreated, unresectable, locally
advanced or metastatic HER2-positive breast cancer, including
patients with or without brain metastases. In addition, tucatinib
is being evaluated in other solid tumor clinical trials, including
colorectal cancer.
About HER2-Positive Metastatic 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.
BreastCancer.org estimates 271,270 new cases of invasive breast
cancer will be diagnosed in the U.S. in 2019.3 Approximately 25
percent of breast cancers are HER2-positive.4 Historically, HER2
disease has been associated with shorter survival times as well as
a higher risk of recurrence and CNS disease (brain metastases).
Approximately 30 to 50 percent of HER2-positive breast cancer
patients develop brain metastases over time.5,6 Over the past two
decades, the approvals of four targeted treatments (trastuzumab,
pertuzumab, lapatinib and T-DM1) have led to improved
progression-free survival and survival rates of patients with
metastatic HER2-positive 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 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 therapeutic
potential of tucatinib, its possible safety, efficacy, and
therapeutic uses and anticipated development activities including
the enrollment of patients in the company’s phase 3 clinical trial
evaluating tucatinib in combination with ado-trastuzumab emtansine
for patients with locally advanced or metastatic HER2+ breast
cancer, development of tucatinib for breast and other cancers,
future clinical trials and intended 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 inability to show
sufficient activity in clinical trials, the risk of adverse events
or safety signals, and the possibility of 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:
- Moulder, S. et al., Phase 1 Trial 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.
- Hamilton, E. et al., Efficacy of a Phase 1b Trial 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 San
Antonio Breast Cancer Symposium (SABCS) Annual Meeting 2016, San
Antonio, TX, December 9, 2016 (Poster P4-21-01).
- BreastCancer.org, U.S. Breast Cancer Statistics. Accessed
August 2019.
- BreastCancer.org, HER2 Status. Accessed August 2019.
- Metro, et al., Clinical outcome of patients with brain
metastases from HER2-positive breast cancer treated with lapatinib
and capecitabine. Annals of Oncology, vol. 212, no. 3, pp. 625-630,
2011.
- Ramakrishna N., et al., Journal of Clinical Oncology 32, no. 19
(July 2014) 2100-2108.
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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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