BOTHELL, Wash. and TOKYO, Sept. 28,
2019 /PRNewswire/ -- Seattle Genetics,
Inc. (Nasdaq: SGEN) and Astellas Pharma Inc. (TSE: 4503,
President and CEO: Kenji Yasukawa,
Ph.D., "Astellas") today announced initial results from the phase 1
clinical trial EV-103. Forty-five patients were evaluated for
safety with the combination of the investigational agent enfortumab
vedotin and the immune therapy pembrolizumab in previously
untreated patients with locally advanced or metastatic urothelial
cancer who were ineligible for treatment with cisplatin-based
chemotherapy. The study met outcome measures for safety and
exhibited encouraging clinical activity for this platinum-free
combination in a first-line setting. The data will be presented
during an oral session today at the European Society for Medical
Oncology (ESMO) 2019 Congress in Barcelona, Spain (Abstract #901O).
Enfortumab vedotin is a first-in-class antibody drug conjugate
(ADC) that targets Nectin-4, a protein present on almost all
urothelial tumor cells and associated with cancer
formation.1
"Advanced urothelial cancer is an aggressive disease for which
more options are needed, especially for patients who are ineligible
for first-line treatment with cisplatin," said Dr. Christopher J. Hoimes, Director, Genitourinary
Oncology, Case Comprehensive Cancer Center at University Hospitals
Seidman Cancer Center, Cleveland,
Ohio. "This study tests the combination of the
investigational agent enfortumab vedotin with the PD-1 inhibitor
pembrolizumab, in a biomarker unselected population. Initial
results provide support for further development of enfortumab
vedotin combinations in this and other settings of urothelial
cancer."
Fifty-one percent of patients (23/45) had an adverse event
greater than or equal to Grade 3. Among these events, an increase
in lipase was the most frequent (13 percent; 6/45). Four patients
(9 percent) discontinued treatment due to treatment-related adverse
events, most commonly peripheral sensory neuropathy. There was one
death deemed to be treatment-related by the investigator attributed
to multiple organ dysfunction syndrome.
Treatment-related adverse events of clinical interest that were
greater than or equal to Grade 3 were rash (11 percent; 5/45),
hyperglycemia (7 percent; 3/45) and peripheral neuropathy (4
percent; 2/45); these rates were similar to those observed with
enfortumab vedotin monotherapy.2 Eleven percent (5/45)
of patients had treatment-related immune-mediated adverse events of
clinical interest greater than or equal to Grade 3 that required
the use of systemic steroids (one event each of pneumonitis,
dermatitis bullous, hyperglycemia, tubulointerstitial nephritis,
myasthenia gravis). None of the adverse events of clinical interest
were Grade 5 events.
The data demonstrated the combination of enfortumab vedotin plus
pembrolizumab shrank tumors in the majority of patients, resulting
in a confirmed objective response rate (ORR) of 71 percent (32/45;
95% Confidence Interval (CI): 55.7, 83.6). The complete response
(CR) rate was 13 percent (6/45). Fifty-eight percent (26/45)
of patients had a partial response and 22 percent (10/45) had
stable disease. Ninety-one percent of responses were observed at
the first assessment.
"These data are encouraging and support further exploration of a
potential platinum-free combination of pembrolizumab and the
investigational agent enfortumab vedotin," said Roger Dansey, M.D., Chief Medical Officer at
Seattle Genetics.
"We are motivated by these results, and we will continue to
study enfortumab vedotin alone and in combination with other agents
in different stages of urothelial cancer," said Andrew Krivoshik, M.D., Ph.D., Senior Vice
President and Oncology Therapeutic Area Head at Astellas.
Enfortumab vedotin is currently under review by the U.S. Food
and Drug Administration (FDA) for the treatment of patients with
locally advanced or metastatic urothelial cancer who have received
a PD-1/L1 inhibitor and who have received a platinum-containing
chemotherapy in a neoadjuvant/adjuvant, locally advanced or
metastatic setting.
About the EV-103 Trial
EV-103 is an ongoing,
multi-cohort, open-label, multicenter phase 1 trial of enfortumab
vedotin alone or in combination, evaluating safety, tolerability
and efficacy in muscle invasive, locally advanced and first- and
second-line metastatic urothelial cancer.
The dose escalation-cohort and expansion cohort A include
locally advanced or metastatic urothelial cancer patients who are
ineligible for cisplatin-based chemotherapy. Patients were dosed in
a 21-day cycle, receiving an intravenous (IV) infusion of
enfortumab vedotin on Days 1 and 8 and pembrolizumab on Day 1. At
the time of this initial analysis, 45 patients (5 from the
dose-escalation cohort and 40 from the dose-expansion cohort A)
with locally advanced and/or metastatic urothelial cancer had been
treated with enfortumab vedotin (1.25 mg/kg) plus pembrolizumab in
the first-line setting.
The primary outcome measure of the cohorts included in this
analysis is safety. The analysis of these first cohorts included
several of the study's secondary objectives. Key secondary
objectives related to efficacy include objective response rate
(ORR), disease control rate (DCR), duration of response (DOR) and
overall survival (OS). DOR and OS were not mature at the time
of analysis and will be included in a future analysis.
Additional cohorts in the EV-103 study will evaluate enfortumab
vedotin:
- with cisplatin or carboplatin in a first-line setting for
metastatic disease;
- in combination with pembrolizumab and carboplatin or cisplatin
in first-line metastatic disease;
- as a monotherapy or in combination with pembrolizumab in muscle
invasive disease;
- with pembrolizumab in second-line metastatic disease; and
- with gemcitabine in first- or second-line metastatic
disease.3
More information about enfortumab vedotin clinical trials can be
found at clinicaltrials.gov.
About Urothelial Cancer
Urothelial cancer is
the most common type of bladder cancer (90 percent of
cases).4 In 2018, more than 82,000 people were diagnosed
with bladder cancer in the United
States. Globally, approximately 549,000 people were
diagnosed with bladder cancer last year, and there were
approximately 200,000 deaths worldwide.5
The recommended first-line treatment for patients with advanced
urothelial cancer is a cisplatin-based chemotherapy. For patients
who are ineligible for cisplatin, such as people with kidney
impairment, a carboplatin-based regimen is recommended. However,
fewer than half of patients respond to carboplatin-based regimens
and outcomes are typically poorer compared to cisplatin-based
regimens.6
About Enfortumab Vedotin
Enfortumab vedotin is an
investigational antibody-drug conjugate (ADC) composed of an
anti-Nectin-4 monoclonal antibody attached to a
microtubule-disrupting agent, MMAE, using Seattle Genetics'
proprietary linker technology. Enfortumab vedotin targets Nectin-4,
a cell adhesion molecule that is expressed on many solid tumors,
and that has been identified as an ADC target by Astellas.
The safety and efficacy of enfortumab vedotin are under
investigation and have not been established. There is no guarantee
that the agent will receive regulatory approval or become
commercially available for the uses being investigated.
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. 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.
About Astellas
Astellas Pharma Inc., based in
Tokyo, Japan, is a company
dedicated to improving the health of people around the world
through the provision of innovative and reliable pharmaceutical
products. For more information, please visit our website at
https://www.astellas.com/en.
About the Astellas and Seattle Genetics Collaboration
Seattle Genetics and Astellas are co-developing enfortumab vedotin
under a collaboration that was entered into in 2007 and expanded in
2009. Under the collaboration, the companies are sharing costs and
profits on a 50:50 basis worldwide.
Seattle Genetics Forward Looking Statement(s)
Certain
statements made in this press release are forward looking, such as
those, among others, relating to the EV-103 clinical trial;
clinical development plans relating to enfortumab vedotin; and the
therapeutic potential of enfortumab vedotin including its possible
safety, efficacy, and therapeutic uses, including in the first-line
setting, and the potential FDA approval of enfortumab vedotin for
the treatment of patients with locally advanced or metastatic
urothelial cancer who have received a PD-1/L1 inhibitor and who
have received a platinum-containing chemotherapy in the
neoadjuvant/adjuvant, locally advanced or metastatic setting.
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
ongoing and subsequent clinical trials of enfortumab vedotin may
fail to establish sufficient efficacy; that adverse events or
safety signals may occur; that adverse regulatory actions or other
setbacks could occur as enfortumab vedotin advances in clinical
trials even after promising results in earlier clinical trials; and
that the Biologics License Application submission and any future
potential supplemental Biologics License Application submissions
for enfortumab vedotin may not be approved by the FDA in a timely
manner or at all or with the requested label(s). 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.
Astellas Cautionary Notes
In this press release,
statements made with respect to current plans, estimates,
strategies and beliefs and other statements that are not historical
facts are forward-looking statements about the future performance
of Astellas. These statements are based on management's current
assumptions and beliefs in light of the information currently
available to it and involve known and unknown risks and
uncertainties. A number of factors could cause actual results to
differ materially from those discussed in the forward-looking
statements. Such factors include, but are not limited to: (i)
changes in general economic conditions and in laws and regulations,
relating to pharmaceutical markets, (ii) currency exchange rate
fluctuations, (iii) delays in new product launches, (iv) the
inability of Astellas to market existing and new products
effectively, (v) the inability of Astellas to continue to
effectively research and develop products accepted by customers in
highly competitive markets, and (vi) infringements of Astellas'
intellectual property rights by third parties.
Information about pharmaceutical products (including products
currently in development), which is included in this press release
is not intended to constitute an advertisement or medical
advice.
1 Vlachostergios P, Jakubowski C, Niaz J, et al.
(2018). Antibody-Drug Conjugates in Bladder Cancer. Bladder Cancer
(Version 4.2018).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087439/pdf/blc-4-blc180169.pdf
2 Rosenberg J. Pivotal Trial of Enfortumab Vedotin in
Urothelial Carcinoma After Platinum and Anti-Programmed Death
1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2019; DOI:
10.1200/JCO.19.01140
3 ClinicalTrials.gov. A Study of Enfortumab Vedotin
Alone or With Other Therapies for Treatment of Urothelial Cancer
(EV-103). https://clinicaltrials.gov/ct2/show/NCT03288545
4 American Society of Clinical Oncology. Bladder Cancer:
Introduction (05-2019).
https://www.cancer.net/cancer-types/bladder-cancer/introduction
5 International Agency for Research on Cancer. Cancer
Tomorrow: Bladder. http://gco.iarc.fr/tomorrow
6 National Comprehensive Cancer Network (NCCN). NCCN
Clinical Practice Guidelines in Oncology: Bladder Cancer. Version
4; July 10, 2019.
https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf
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