CORRECTING and REPLACING Seattle Genetics Announces Publication of Results from Two Tucatinib Phase 1b Clinical Trials in HER2-Positive Metastatic Breast Cancer

The second bullet point above the “About Tucatinib” boilerplate, should
read: “ORR was 47 percent (n=16/34)” (instead of “ORR was 47 percent

The corrected release reads:


Results of Combination “Triplet” of Tucatinib with Trastuzumab and
Capecitabine Published in The Lancet Oncology

Results of Tucatinib in Combination with Ado-trastuzumab Emtansine
Published in JAMA Oncology

Genetics, Inc. (Nasdaq:SGEN) today announced that results of a phase
1b clinical trial of tucatinib in combination with standard of care
agents for the treatment of patients with advanced HER2-positive (HER2+)
metastatic breast cancer were recently published in the journal The
Lancet Oncology. Results demonstrated that tucatinib in combination
with trastuzumab (Herceptin®) and capecitabine (Xeloda®)
was generally well-tolerated and had encouraging clinical activity in
heavily pre-treated patients with advanced HER2+ breast cancer,
including those with brain metastases (ONT-380-005/triplet study). A
separate phase 1b clinical trial of tucatinib in combination with
ado-trastuzumab emtansine (T-DM1, Kadcyla®) was published in JAMA
Oncology. Results showed an acceptable safety profile and
preliminary antitumor activity among heavily pretreated patients with
HER2+ metastatic breast cancer, with and without brain metastases
(ONT-380-004). Tucatinib is an oral, small molecule tyrosine kinase
inhibitor that is highly selective for HER2.

“There remains a need for a well-tolerated, oral targeted therapy to
treat patients with HER2+ metastatic breast cancer whose disease
progresses on conventional anti-HER2 treatments, particularly for those
whose cancer has metastasized to the brain, which occurs in up to 50
percent of these patients,” said Rashmi Murthy, M.D., MBE, Assistant
Professor, Department of Breast Medical Oncology, Division of Cancer
Medicine, The University of Texas MD Anderson Cancer Center. “In the
ONT-380-005 triplet study, durable responses were seen in heavily
pretreated patients with metastatic HER2+ breast cancer, including those
with brain metastases, after treatment with tucatinib. Importantly, in
the trial, tucatinib treatment was associated with few clinically
significant side effects, such as diarrhea or skin rash, commonly seen
with other tyrosine kinase inhibitors targeting this disease, which may
allow for prolonged use and as a result potentially improve outcomes for

“The results of the combination tucatinib with trastuzumab and
capecitabine triplet study support the development of this regimen in
the ongoing pivotal HER2CLIMB trial to provide a meaningful advancement
in the use of targeted therapies to treat this disease,” said Roger
Dansey, M.D., Chief Medical Officer at Seattle Genetics. “In addition,
based on the results of the combination of tucatinib with T-DM1, we are
evaluating development opportunities for this combination in earlier
lines of HER2+ metastatic breast cancer.”

The manuscript entitled “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” was published
in the July print edition of The Lancet Oncology.

The phase 1b triplet study was an open-label dose-escalation and
expansion cohort study of tucatinib in combination with capecitabine
and/or trastuzumab in patients with HER2+ metastatic breast cancer,
including those with or without brain metastases. The objective of the
study was to assess the safety, tolerability, pharmacokinetics and
antitumor activity, and to determine the recommended phase 2 dose of
tucatinib in combination with these agents. Once a recommended phase 2
dose of 300 mg BID was established in the triplet combination, an
expansion cohort using that regimen was opened. The trial enrolled 60
patients with HER2+ metastatic breast cancer who had previously received
a median of three HER2-targeted agents, such as trastuzumab, pertuzumab
(Perjeta®), lapatinib (Tykerb®) or T-DM1.

Data from patients treated with the triplet combination at 300 mg BID
(n=27) included:

An ongoing randomized, double-blind, placebo-controlled pivotal trial
called HER2CLIMB
is comparing tucatinib vs. placebo, each in combination with
capecitabine and trastuzumab in patients with pretreated, unresectable,
locally advanced or metastatic HER2+ breast cancer, including patients
with or without brain metastases.

“The combination of tucatinib and T-DM1 in the phase 1b clinical
trial was tolerable and appeared to show antitumor activity among
heavily pretreated patients with HER2+ metastatic breast cancer with and
without brain metastases,” said Virginia Borges, M.D., Deputy Head of
the Division of Medical Oncology and the Robert F. & Patricia Young
Endowed Chair in Young Women’s Breast Cancer Research at the University
of Colorado School of Medicine. “Based on these data, tucatinib may have
the potential to be a new therapeutic option for these patients and
warrants further investigation.”

The manuscript entitled “Tucatinib combined with ado-trastuzumab
emtansine in advanced HER2-positive metastatic breast cancer: A phase 1b
open-label clinical trial” was published in the July print edition of JAMA

This phase 1b, open-label dose escalation and expansion cohort study of
tucatinib in combination with T-DM1 enrolled 57 patients with HER2+
breast cancer. The objective of the study was to assess the safety,
tolerability, pharmacokinetics and antitumor activity, and to determine
the recommended phase 2 dose of tucatinib in combination with
T-DM1. Participants in the study previously received a median of two
prior HER2-directed therapies.

Data from the phase 1b study of tucatinib and T-DM1 (n=57) included:

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 U.S. Food and Drug Administration (“FDA”) for the
treatment of breast cancer patients with brain metastases.

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. The American
Cancer Society estimates 268,670 new cases of invasive breast cancer
will be diagnosed in the U.S. in 2018. Approximately 15 to 20 percent of
breast cancers are HER2-positive.3 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.4,5 Over the past two decades, the approvals of
four targeted treatments (trastuzumab, pertuzumab, lapatinib and T-DM1)
have led to improved time to progression and survival rates of patients
with 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
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 continued enrollment of
patients in HER2CLIMB, 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 the 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
March 31, 2018 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.


1. 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.

2. 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).

3. ASCO Cancer.Net, Treatment of Metastatic HER2-Positive Breast Cancer.
Accessed July 2018.

4. 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.

5. Ramakrishna N., et al., Journal of Clinical Oncology 32, no.
19 (July 2014) 2100-2108.

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