THOUSAND OAKS, Calif.,
Oct. 5, 2017 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that the Journal of Clinical
Oncology has published positive results from the
IMLYGIC® (talimogene laherparepvec) Phase 2 '264
study. The study met its primary endpoint of objective response
rate (ORR), demonstrating that IMLYGIC in combination with
YERVOY® (ipilimumab) more than doubled ORR,
defined as the proportion of patients with tumor size reduction,
compared to ipilimumab alone in patients with unresectable stage
IIIB-IV melanoma (39 percent versus 18 percent; odds ratio=2.9, 95
percent CI: 1.5, 5.5; p=0.002). Patients in the combination
arm also experienced nearly double the complete response rate
compared to ipilimumab alone (13 percent versus 7 percent).
"Advanced melanoma is highly aggressive and can require multiple
treatment approaches over the course of the disease," said
Jason Chesney, M.D., lead author of
the '264 study and director of the James Graham Brown Cancer
Center, University of Louisville,
Louisville, Ky. "Results from the
study found that administration of IMLYGIC in combination with
ipilimumab led to greater efficacy versus ipilimumab alone in both
uninjected and visceral lesions. These data show that this
combination of a checkpoint inhibitor plus IMLYGIC demonstrated a
synergistic clinical effect and enhanced anti-tumor immune response
in patients with metastatic melanoma."
IMLYGIC is designed to rupture cancer cells causing the release
of tumor-derived antigens, which along with granulocyte-macrophage
colony-stimulating factor (GM-CSF), may help to initiate an
anti-tumor immune response. However, the exact mechanism of action
is unknown. This may be complementary to ipilimumab's mechanism of
action, as the blockade of cytotoxic T-lymphocyte-associated
antigen-4 has been shown to augment activation and proliferation of
tumor infiltrating T-effector cells.
Melanoma is one of the most dangerous types of skin cancers,
especially when it spreads to other parts of the body.1
The study showed that responses occurred in both injected and
uninjected lesions, including visceral lesions, demonstrating a
systemic anti-tumor response. Thirty-one (32 percent) and 22 (22
percent) of the patients were shown to have visceral disease at
baseline in the combination and ipilimumab arms, respectively. Of
these patients, 16 (52 percent) in the combination arm and five (23
percent) in the ipilimumab arm were observed to have a decrease in
visceral lesion tumor burden. Patients in the combination arm also
experienced a median progression-free survival (PFS) of 8.2 months
(median follow up 68 weeks) versus 6.4 months in the ipilimumab
arm. The effect was not statistically significant (HR=0.83, 95
percent CI: 0.56, 1.23; p=0.35); however, the PFS analysis
was not event-driven and is still ongoing. Evaluation of overall
survival (OS) is ongoing and continues to be monitored.
The most common adverse events in the IMLYGIC plus ipilimumab
arm compared to the ipilimumab alone arm were fatigue (59 percent
versus 42 percent, respectively), chills (53 percent versus 3
percent, respectively), diarrhea (42 percent versus 35 percent,
respectively), pruritus (40 percent versus 36 percent,
respectively), rash (39 percent versus 28 percent, respectively)
and nausea (38 percent versus 24 percent, respectively).
"IMLYGIC is the first and only approved oncolytic viral therapy
in the U.S. and Europe,
reinforcing Amgen's leadership and commitment to developing
innovative therapies for difficult-to-treat cancers," said
Sean E. Harper, M.D., executive vice
president of Research and Development at Amgen. "The data published
today in the Journal of Clinical Oncology supports the
scientific hypothesis behind the combination of IMLYGIC with an
immune checkpoint inhibitor. We are excited about the promise of
our diverse immuno-oncology pipeline that looks at combinations
that may be effective in stimulating an immune attack on cancer
cells."
In the study, response rate was also higher in the combination
arm across subsets of the disease. ORR for patients with stage
IIIB/IIIC/IVM1a disease was 44 percent in the combination arm and
19 percent in the ipilimumab arm (overall response [OR]=3.3, 95
percent CI: 1.4, 7.8; p=0.007). In patients with stage
IVM1b/IVM1c disease, ORR was 33 percent and 16 percent,
respectively (OR=2.6, 95 percent CI: 0.9, 7.0; p=0.09).
Among BRAF wild-type patients, ORR was 42 percent in the
combination arm versus 10 percent in the ipilimumab arm (OR=6.5, 95
percent CI: 2.4, 17.4; p<0.0001). In patients with
BRAF-mutant tumors, which comprised a minority of each arm
at 35 (36 percent) and 34 (34 percent) for the combination and
ipilimumab arms respectively, ORR was 34 percent in the combination
arm versus 32 percent in the ipilimumab arm (OR=1.1, 95 percent CI:
0.4, 3.0; p=1.0). The disease control rate (DCR) was 58
percent in the combination arm and 42 percent in the ipilimumab arm
(OR=1.9, 95 percent CI: 1.1, 3.4; p=0.033). DCR in all
subgroups, with the exception of patients with BRAF
mutations, favored the combination arm.
About the '264 Study
The '264 study is a Phase 1b/2, multicenter, open-label trial
evaluating the safety and efficacy of IMLYGIC in combination with
ipilimumab compared to ipilimumab alone in patients with
unresectable stage IIIB-IV melanoma. The primary endpoint of the
Phase 2 portion of study is ORR. Secondary endpoints include
duration of response, DCR, PFS, OS and safety. The study randomized
198 patients, 98 in the IMLYGIC plus ipilimumab arm and 100 in the
ipilimumab arm.
About Metastatic Melanoma
Melanoma remains a significant public health concern across the
globe. Unlike some other cancers, melanoma incidence rates have
doubled in the past 40 years, with 132,000 cases occurring
worldwide each year.2,3 Melanoma is more dangerous than
other skin cancers, especially when it spreads to other parts of
the body, which is referred to as metastatic disease.1
The overall five-year risk of relapse after surgery increases as
disease stage advances, from 48 percent for stage IIIA to 85
percent for stage IIIC.4 Risk of recurrence is even
higher for patients in stage IV undergoing surgery, with 91 percent
experiencing relapse.5 Despite new options, additional
treatments are needed – particularly for patients with metastatic
disease.
About IMLYGIC® (talimogene
laherparepvec)
IMLYGIC is a genetically modified herpes simplex type 1 virus
that is injected directly into tumors. IMLYGIC replicates inside
tumor cells and produces GM-CSF, an immunostimulatory protein.
IMLYGIC then causes the cell to rupture and die in a process called
lysis. The rupture of the cancer cells causes the release of
tumor-derived antigens, which together with virally derived GM-CSF
may help to promote an anti-tumor immune response. However, the
exact mechanism of action is unknown.
IMLYGIC is the first oncolytic viral therapy approved by the
U.S. Food and Drug Administration (FDA) based on therapeutic
benefit demonstrated in a pivotal study. IMLYGIC is a genetically
modified oncolytic viral therapy indicated for the local treatment
of unresectable cutaneous, subcutaneous, and nodal lesions in
patients with melanoma recurrent after initial surgery. IMLYGIC has
not been shown to improve OS or have an effect on visceral
metastases.
Important U.S. Safety Information
Contraindications
- Do not administer IMLYGIC® to immunocompromised
patients, including those with a history of primary or acquired
immunodeficient states, leukemia, lymphoma, AIDS or other clinical
manifestations of infection with human immunodeficiency viruses,
and those on immunosuppressive therapy, due to the risk of
life‐threatening disseminated herpetic infection.
- Do not administer IMLYGIC® to pregnant
patients.
Warnings and Precautions
- Accidental exposure to IMLYGIC® may lead to
transmission of IMLYGIC® and herpetic infection,
including during preparation and administration. Health care
providers, close contacts, pregnant women, and newborns should
avoid direct contact with injected lesions, dressings, or body
fluids of treated patients. The affected area in exposed
individuals should be cleaned thoroughly with soap and water and/or
a disinfectant.
- Caregivers should wear protective gloves when assisting
patients in applying or changing occlusive dressings and observe
safety precautions for disposal of used dressings, gloves, and
cleaning materials. Exposed individuals should clean the affected
area thoroughly with soap and water and/or a disinfectant.
- To prevent possible inadvertent transfer of IMLYGIC®
to other areas of the body, patients should be advised to avoid
touching or scratching injection sites or occlusive dressings.
- Herpetic infections: Herpetic infections (including cold
sores and herpetic keratitis) have been reported in
IMLYGIC®‐treated patients. Disseminated herpetic
infection may also occur in immunocompromised patients. Patients
who develop suspicious herpes-like lesions should follow standard
hygienic practices to prevent viral transmission.
- Patients or close contacts with suspected signs or symptoms of
a herpetic infection should contact their health care provider to
evaluate the lesions. Suspected herpetic lesions should be reported
to Amgen at 1-855-IMLYGIC (1-855-465-9442). Patients or close
contacts have the option of follow-up testing for further
characterization of the infection.
- IMLYGIC® is sensitive to acyclovir. Acyclovir or
other antiviral agents may interfere with the effectiveness of
IMLYGIC®. Consider the risks and benefits of
IMLYGIC® treatment before administering antiviral agents
to manage herpetic infection.
- Injection Site Complications: Necrosis or ulceration of
tumor tissue may occur during IMLYGIC® treatment.
Cellulitis and systemic bacterial infection have been reported in
clinical studies. Careful wound care and infection precautions are
recommended, particularly if tissue necrosis results in open
wounds.
- Impaired healing at the injection site has been reported.
IMLYGIC® may increase the risk of impaired healing in
patients with underlying risk factors (e.g., previous radiation at
the injection site or lesions in poorly vascularized areas). If
there is persistent infection or delayed healing of the injection
site, consider the risks and benefits of continuing treatment.
- Immune-Mediated events including
glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis,
and vitiligo have been reported in patients treated with
IMLYGIC®. Consider the risks and benefits of
IMLYGIC® before initiating treatment in patients who
have underlying autoimmune disease or before continuing treatment
in patients who develop immune-mediated events.
- Plasmacytoma at the Injection Site: Plasmacytoma in
proximity to the injection site has been reported in a patient with
smoldering multiple myeloma after IMLYGIC®
administration in a clinical study. Consider the risks and benefits
of IMLYGIC® in patients with multiple myeloma or in whom
plasmacytoma develops during treatment.
- Obstructive Airway Disorder: Obstructive airway disorder
has been reported following IMLYGIC® treatment. Use
caution when injecting lesions close to major airways.
Adverse Reactions
- The most commonly reported adverse drug reactions (≥ 25%) in
IMLYGIC®-treated patients were fatigue, chills, pyrexia,
nausea, influenza-like illness, and injection site pain. Pyrexia,
chills, and influenza-like illness can occur at any time during
IMLYGIC® treatment, but were more frequent during the
first 3 months of treatment.
- The most common Grade 3 or higher adverse reaction was
cellulitis.
Please see full Prescribing Information and Medication Guide for
IMLYGIC®.
About Amgen's Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the
toughest cancers, such as those that have been resistant to drugs,
those that progress rapidly through the body and those where
limited treatment options exist. Amgen's supportive care
treatments help patients combat certain side effects of strong
chemotherapy, and our targeted medicines and immunotherapies focus
on more than a dozen different malignancies, ranging from blood
cancers to solid tumors. With decades of experience providing
therapies for cancer patients, Amgen continues to grow
its portfolio of innovative and biosimilar oncology medicines.
About Amgen
Amgen is committed to unlocking the potential of biology for
patients suffering from serious illnesses by discovering,
developing, manufacturing and delivering innovative human
therapeutics. This approach begins by using tools like advanced
human genetics to unravel the complexities of disease and
understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and
leverages its expertise to strive for solutions that improve health
outcomes and dramatically improve people's lives. A biotechnology
pioneer since 1980, Amgen has grown to be one of the
world's leading independent biotechnology companies, has reached
millions of patients around the world and is developing a pipeline
of medicines with breakaway potential.
For more information, visit www.amgen.com and follow
us on www.twitter.com/amgen.
Forward-Looking Statements
This news release contains forward-looking statements that are
based on the current expectations and beliefs of Amgen. All
statements, other than statements of historical fact, are
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including estimates of revenues, operating margins, capital
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results. Forward-looking statements involve significant risks
and uncertainties, including those discussed below and more fully
described in the Securities and Exchange
Commission reports filed by Amgen, including our most
recent annual report on Form 10-K and any subsequent periodic
reports on Form 10-Q and Form 8-K. Unless otherwise
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of this news release and does not undertake any obligation to
update any forward-looking statements contained in this document as
a result of new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual
results may differ materially from those we project. Discovery or
identification of new product candidates or development of new
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from concept to product is uncertain; consequently, there can be no
guarantee that any particular product candidate or development of a
new indication for an existing product will be successful and
become a commercial product. Further, preclinical results do not
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sometimes, even adequately modeled by computer or cell culture
systems or animal models. The length of time that it takes for us
to complete clinical trials and obtain regulatory approval for
product marketing has in the past varied and we expect similar
variability in the future. Even when clinical trials are
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approval of the trial endpoints we have selected. We develop
product candidates internally and through licensing collaborations,
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Our results may be affected by our ability to successfully
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Our stock price is volatile and may be affected by a number of
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The scientific information discussed in this news release
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The products are not approved for the investigational use(s)
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*YERVOY is marketed by Bristol-Myers Squibb
CONTACT:
Amgen, Thousand Oaks
Kristen Davis, 805-447-3008
(media)
Kristen Neese, 805-313-8267
(media)
Arvind Sood, 805-447-1060
(investors)
References:
- American Cancer Society. Melanoma Skin Cancer.
http://www.cancer.org/acs/groups/cid/documents/webcontent/003120-pdf.pdf.
Accessed April 17, 2017.
- World Health Organization. How common is skin cancer?
http://www.who.int/uv/faq/skincancer/en/index1.html. Accessed
April 17, 2017.
- AIM at Melanoma Foundation. Melanoma Stats, Facts, and Figures.
http://www.aimatmelanoma.org/about-melanoma/melanoma-stats-facts-and-figures/.
Accessed April 17, 2017.
- Romano E et al. Site and timing of first relapse in stage III
melanoma patients: implications for follow-up guidelines. J Clin
Oncol. 2010;28:3042-3047.
- Sosman JA, Moon J, Tuthill RJ, et al. A phase 2 trial of
complete resection for stage IV melanoma: results of Southwest
Oncology Group Clinical Trial S9430. Cancer.
2011;117:4740-4706.
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