[ad_1]
BOTHELL, Wash .– ( BUSINESS SONGS ) – The second point above the boilerplate "About Tucatinib" should
read: "ORR was 47 percent (n = 16/34)" (instead of "ORR was 47 percent
(n = 34/50) ").
The corrected version states:
SEATTLE GENETICS ANNOUNCES PUBLICATION OF THE RESULTS OF TWO TUCATINIB
CLINICAL TRIALS OF PHASE 1B IN HER2-POSITIVE METASTATIC BREAST CANCER
Results of the "Triplet" combination of Tucatinib with Trastuzumab and
Capecitabine Published in The Lancet Oncology
Results of Tucatinib in association with Ado-trastuzumab Emtansine
Posted on JAMA Oncology
Seattle
Genetics, Inc. (Nasdaq: SGEN) announced today that the results of one 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 . The results demonstrated that tucatinib in combination
with trastuzumab (Herceptin ® ) and capecitabine (Xeloda ® )
was generally well tolerated and had encouraging clinical activity
heavily pretreated patients with advanced HER2 + breast cancer,
including those with brain metastases (ONT-380-005 / triplet study). A
phase 1b separate clinical trial of tucatinib in combination with
The ado-trastuzumab emtansine (T-DM1, Kadcyla ® ) was published in JAMA
Oncology . The results showed an acceptable safety profile and
preliminary antitumor activity in heavily pre-treated patients with
HER2 + metastatic breast cancer, with or without brain metastases
(ONT-380-004). Tucatinib is a small molecule tyrosine kinase administered orally.
highly selective inhibitor for HER2.
"There remains a need for a well-tolerated oral targeted therapy for
treat patients with metastatic HER2 + breast cancer whose disease
progresses on conventional anti-HER2 treatments, particularly for
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, Cancer Division
Medicine, University of Texas MD Anderson Cancer Center. "In the
ONT-380-005 triplet study, long-lasting responses were observed
Pretreated patients with metastatic HER2 + breast cancer, including
with cerebral metastases, after treatment with tucatinib. Especially in
the trial, tucatinib treatment was associated with little
side effects, such as diarrhea or rash, often
with other tyrosine kinase inhibitors targeting this disease, which can
allow for prolonged use and, therefore, potentially improve the results for
patients. "
"The results of the tucatinib association with trastuzumab and
triplet study of capecitabine supports the development of this diet
ongoing HER2CLIMB pivotal trial to provide meaningful advancement
in the use of targeted therapies to treat this disease, "said Roger
Dansey, M.D., chief physician at Seattle Genetics. "In addition,
based on the results of the combination of tucatinib with T-DM1, we are
evaluate the development opportunities of this combination
HER2 + metastatic breast cancer lines. "
The manuscript entitled" Tucatinib with capecitabine and trastuzumab in
HER2-positive advanced metastatic breast cancer with and without brain
metastases: a non-randomized open-label phase 1b study published
in the July printed edition of The Lancet Oncology .
The phase 1b triplet study was an open dose-escalation and
expansion cohort study of tucatinib in combination with capecitabine
and / or trastuzumab in patients with metastatic HER2 + breast cancer,
including those with or without brain metastases. The goal of the
The study aimed to evaluate the safety, tolerability, pharmacokinetics and
antitumor activity, and to determine the recommended phase 2 dose
tucatinib in combination with these agents. Once a recommended phase 2
dose of 300 mg BID was established in the triplet combination, a
Cohort of expansion using this scheme has been opened. The test is registered 60
patients with HER2 + metastatic breast cancer who had already received
a median of three HER2 targeting agents, such as trastuzumab, pertuzumab
(Perjeta ® ), lapatinib (Tykerb ® ) or T-DM1.
Data from patients treated with triplet combination at 300 mg BID
(n = 27) included:
- The median progression-free survival (PFS) was 7.8 months.
-
The objective response rate (ORR) was 61% (n = 14/23) with a median
duration of the response of 11.0 months. - Median PFS for patients with brain metastases (n = 11) was 6.7 months.
-
ORR was 42 percent (n = 5/12) in patients with a measurable brain
metastases receiving the 300 mg dose of tucatinib in
combination. -
The combination of triplets was well tolerated and the majority of
events were grade 1, with most patients able to continue
full dose of tucatinib. Grade 3 diarrhea was rare without
requirement of a prophylactic anti-diarrheal medicine.
On-going randomized clinical trial, double-blind, placebo-controlled
called HER2CLIMB
compares tucatinib to placebo, each in combination with
capecitabine and trastuzumab in pretreated, unresectable patients,
HER2 + locally advanced or metastatic breast cancer, including patients
with or without brain metastases.
"The combination of tucatinib and T-DM1 in clinical phase 1b
the test was tolerable and appeared to show antitumor activity in
heavily pretreated patients with metastatic HER2 + breast cancer with and
without brain metastases, "said Virginia Borges, M.D., deputy chief of
the Division of Medical Oncology and the Robert F. and Patricia Young
Research Chair on Breast Cancer in Young Women at the University
from the Colorado School of Medicine. "Based on these data, tucatinib may have
the potential to be a new therapeutic option for these patients and
warrant further investigation. "
The manuscript entitled" Tucatinib combined with ado-trastuzumab
emtansine in HER2-positive advanced metastatic breast cancer: A phase 1b
Open Clinical Trial "was published in the July print edition of JAMA
Oncology .
This phase 1b, open cohort study of dose escalation and expansion of
Tucatinib in combination with T-DM1 included 57 patients with HER2 +
breast cancer. The purpose 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 have already received a median of two
previous treatments HER2.
Phase 1b study data for tucatinib and T-DM1 (n = 57) included:
- The median PFS was 8.2 months.
- ORR was 47 percent (n = 16/34).
-
The combination of tucatinib and T-DM1 was well tolerated and the
the majority of adverse events were grade 1.
About tucatinib
Tucatinib is a potent, experimental, bioavailable tyrosine
kinase inhibitor that is very selective for HER2 without significant
inhibition of EGFR. The inhibition of EGFR has been associated with
significant toxicities, including rashes and diarrhea. Tucatinib has
activity shown as a single agent and in combination with both
chemotherapy and other agents directed against HER2 such as trastuzumab. 1,2
Tucatinib studies in these combinations showed one activity at a time
systemic and in brain metastases. HER2 is a growth factor receptor
which is overexpressed in several cancers, including breast, ovarian and
gastric cancers. HER2 is involved in cell growth, differentiation and
survival. Tumors that overexpress HER2 are more aggressive and
historically have been associated with low overall survival, relative to
with HER2-negative cancers. Tucatinib has been approved orphan drug
designation by the United States Food and Drug Administration ("FDA") for the
treatment of patients with breast cancer 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. L & # 39; American
Canadian Cancer Society evaluates 268,670 new cases of invasive breast cancer
will be diagnosed in the United States in 2018. About 15 to 20 percent of
breast cancers are HER2-positive 3 Historically, HER2 disease
has been associated with shorter survival times as well as higher risk
recurrence and CNS disease (brain metastases). About 30 to 50
percent of patients with HER2-positive breast cancer develop brain metastases
over time. 4.5 During the last two decades, the approvals of
four targeted treatments (trastuzumab, pertuzumab, lapatinib and T-DM1)
lead to improved progression time and patient survival rates
with HER2-positive breast cancer. Despite these advances, there is still
an important need for new therapies that may have an impact on metastatic diseases,
including brain metastases, and be tolerated for longer periods of time.
About Seattle Genetics
Seattle Genetics, Inc. is an emerging global multi-product
biotechnology company that develops and markets transformative
therapies targeting cancer to make a significant difference in the population
lives. ADCETRIS® (brentuximab vedotin) uses the
The best antibody-drug conjugate (ADC) technology in the industry
currently approved for the treatment of several CD30 expressing
lymphomas. Beyond ADCETRIS, the company has established a pipeline of
new therapies targeted at various stages of clinical trials,
of which three in ongoing pivotal trials for solid tumors. Enfortumab
vedotine for metastatic urothelial cancer and tisotumab
Cervical cancer of the metastatic uterus uses our proprietary ADC technology.
Tucatinib, a small tyrosine kinase inhibitory molecule, is
test for HER2-positive metastatic breast cancer. In addition, we are
leveraging our expertise in the antibodies enabled to build a portfolio of
exclusive immuno-oncological 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
Some of the statements made in this press release are advanced
looking, such as those, among others, relating to the therapeutic potential
tucatinib, its possible uses in terms of safety, efficacy and safety.
planned development activities, including the continued listing of
HER2CLIMB patients, development of tucatinib for breast and other
cancers, future clinical trials and planned regulatory measures. Real
results or developments may differ materially from those projected or
implied in these forward-looking statements. Factors that can cause such
a difference includes the difficulty and uncertainty of the pharmaceutical
product development, including the inability to show sufficient activity
in clinical trials, the risk of adverse events or safety signals,
and the potential for adverse regulatory action as tucatinib progresses
in clinical trials even after promising results in the early
trials. More information on the risks and uncertainties encountered by
Seattle Genetics is included under the legend "Risk Factors" included
in the company's quarterly report on Form 10-Q for the quarter ended the
March 31, 2018 filed with the Securities and Exchange
Commission. Seattle Genetics disclaims any intent or obligation to
update or revise any forward-looking statement, whether as a result of
new information, future events or others.
References:
1. Moulder, S. et al., Phase 1 of the ONT-380 Study, an inhibitor of
Patients with HER2 + advanced solid tumors, with a cohort of expansion into
HER2 + metastatic breast cancer. Clin Cancer Res, May 2017.
2. Hamilton, E. et al., Efficacy of a Tucatinib Phase 1b Trial
(ONT-380), a specific oral HER2 inhibitor, in combination with
Capecitabine and Trastuzumab in metastatic HER2 + breast cancer,
Including patients with brain metastases . Presented at the San
Annual Meeting of the Antonio Breast Cancer Symposium (SABCS) 2016, San
Antonio, TX, December 9, 2016 (Poster P4-21-01).
3. ASCO Cancer.Net, treatment of HER2-positive metastatic breast cancer.
Accessed in July 2018.
4. Metro, et al., Clinical outcomes of patients with brain metastases
of 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.
Source link
