THOUSAND OAKS, Calif.,
Sept. 27, 2019 /PRNewswire/
-- Amgen (NASDAQ: AMGN) today announced new data from the
ongoing Phase 1 study evaluating AMG 510 in patients with
previously treated KRAS G12C-mutant solid tumors. The data
include the first evidence of anti-tumor activity reported in
patients with colorectal cancer (CRC) and appendiceal cancer, as
well as previously presented non-small cell lung cancer (NSCLC)
findings. AMG 510 continues to be well-tolerated with no
dose-limiting toxicities. These data are being presented
during a poster discussion at the European Society for Medical
Oncology (ESMO) 2019 Congress.
The study enrolled 76 patients with KRAS G12C-mutant
solid tumors. Data being presented at ESMO include a subset of 55
evaluable patients as of the July
2019 data cutoff, including CRC, appendiceal cancer and
NSCLC patients from the Phase 1 study. Of the 55 patients, 29 had
CRC. Twelve patients with CRC received the target dose of 960 mg
once daily and 10 remain on treatment. One patient in this dose
cohort experienced a partial response and 10 had stable disease for
a disease control rate of 92%. Thirteen of the evaluable patients
with NSCLC received 960 mg, of which seven (54%) achieved a partial
response at one or more timepoints and six (46%) achieved stable
disease, for a disease control rate of 100%. Data across dosing
cohorts also showed tumor responses in two evaluable patients with
appendiceal cancer with one partial response and one experiencing
stable disease.
"KRAS is the most frequently mutated oncogene in human
tumors. Although KRASG12C has been a formidable target
for nearly four decades, we can now report responses in patients
with non-small cell lung, colorectal and appendiceal cancers," said
David M. Reese, M.D., executive vice
president of Research and Development at Amgen. "We are encouraged
by these early results, particularly since these patients have
progressed after receiving a median of four prior therapies, and in
some cases as many as 10. The data suggest there are relevant
molecular differences between tumor types. We are initiating
combination studies to further explore the potential of AMG 510 in
lung and colorectal tumors."
Among the 76 patients enrolled across treatment groups, 52
remain on treatment. The majority of treatment-related adverse
events (TRAEs) were grade 1 and 2. Only two TRAEs were grade 3
(diarrhea and anemia). There were no grade 4 or higher TRAEs.
"The prognosis for patients with advanced colorectal cancer
remains poor," said Marwan G. Fakih,
M.D., clinical study investigator and co-director of the
Gastrointestinal Cancer Program, City of Hope, Duarte, Calif. "These are heavily pre-treated
colorectal cancer patients, with a median progression-free survival
of just over two months, so to see patients still on treatment at
the target dose after more than three months is very
encouraging."
About the Phase 1 Study
The Phase 1, first-in-human,
open-label multicenter study enrolled patients with KRAS
G12C- mutant solid tumors. Eligible patients were heavily
pretreated with at least two or more prior lines of treatment,
consistent with their tumor type and stage of disease. The primary
endpoint is safety, and key secondary endpoints include
pharmacokinetics, objective response rate (assessed every six
weeks), duration of response and progression-free survival.
Patients were enrolled in four dose cohorts: 180 mg, 360 mg, 720 mg
and 960 mg, taken orally once a day.
When evaluating tumor response, a partial response was defined
by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as at
least a 30% decrease in the sum of the diameters of target
lesions.1 Stable disease was defined as having neither
sufficient tumor shrinkage to qualify for a partial response nor
sufficient increase to qualify for progressive disease.
About KRAS
The subject of almost four decades
of research, the RAS gene family are the most frequently
mutated oncogenes in human cancers.2,3 Within this
family, KRAS is the most prevalent variant and is
particularly common in solid tumors.3 A specific
mutation known as KRAS G12C is found in approximately 13% of
non-small cell lung cancers, three to five percent of colorectal
cancers and one to two percent of numerous other solid
tumors.4 Approximately 30,000 patients are diagnosed
each year in the United States
with KRAS G12C-mutant cancers.5
KRASG12C has been considered "undruggable" due to a lack
of traditional small molecule binding pockets on the protein. Amgen
is exploring the potential of KRASG12C inhibition across
a broad variety of tumor types.
About Amgen Oncology
Amgen Oncology is searching for
and finding answers to incredibly complex questions that will
advance care and improve lives for cancer patients and their
families. Our research drives us to understand the disease in the
context of the patient's life – not just their cancer journey – so
they can take control of their lives.
For the last four decades, we have been dedicated to discovering
the firsts that matter in oncology and to finding ways to reduce
the burden of cancer. Building on our heritage, Amgen continues to
advance the largest pipeline in the Company's history, moving with
great speed to advance those innovations for the patients who need
them.
At Amgen, we are driven by our commitment to transform the lives
of cancer patients and keep them at the center of everything we
do.
For more information, follow us on
www.twitter.com/amgenoncology.
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 statements that could be deemed
forward-looking statements, including estimates of revenues,
operating margins, capital expenditures, cash, other financial
metrics, expected legal, arbitration, political, regulatory or
clinical results or practices, customer and prescriber patterns or
practices, reimbursement activities and outcomes and other such
estimates and 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 current reports on Form 8-K. Unless otherwise noted, Amgen
is providing this information as of the date 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 indications for existing products cannot be
guaranteed and movement 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 guarantee safe and effective
performance of product candidates in humans. The complexity of the
human body cannot be perfectly, or 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 successful, regulatory authorities may question
the sufficiency for approval of the trial endpoints we have
selected. We develop product candidates internally and through
licensing collaborations, partnerships and joint ventures. Product
candidates that are derived from relationships may be subject to
disputes between the parties or may prove to be not as effective or
as safe as we may have believed at the time of entering into such
relationship. Also, we or others could identify safety, side
effects or manufacturing problems with our products, including our
devices, after they are on the market.
Our results may be affected by our ability to successfully
market both new and existing products domestically and
internationally, clinical and regulatory developments involving
current and future products, sales growth of recently launched
products, competition from other products including biosimilars,
difficulties or delays in manufacturing our products and global
economic conditions. In addition, sales of our products are
affected by pricing pressure, political and public scrutiny and
reimbursement policies imposed by third-party payers, including
governments, private insurance plans and managed care providers and
may be affected by regulatory, clinical and guideline developments
and domestic and international trends toward managed care and
healthcare cost containment. Furthermore, our research, testing,
pricing, marketing and other operations are subject to extensive
regulation by domestic and foreign government regulatory
authorities. Our business may be impacted by government
investigations, litigation and product liability claims. In
addition, our business may be impacted by the adoption of new tax
legislation or exposure to additional tax liabilities. If we fail
to meet the compliance obligations in the corporate integrity
agreement between us and the U.S. government, we could become
subject to significant sanctions. Further, while we routinely
obtain patents for our products and technology, the protection
offered by our patents and patent applications may be challenged,
invalidated or circumvented by our competitors, or we may fail to
prevail in present and future intellectual property litigation. We
perform a substantial amount of our commercial manufacturing
activities at a few key facilities, including in Puerto Rico, and also depend on third parties
for a portion of our manufacturing activities, and limits on supply
may constrain sales of certain of our current products and product
candidate development. We rely on collaborations with third parties
for the development of some of our product candidates and for the
commercialization and sales of some of our commercial products. In
addition, we compete with other companies with respect to many of
our marketed products as well as for the discovery and development
of new products. Further, some raw materials, medical devices and
component parts for our products are supplied by sole third-party
suppliers. Certain of our distributors, customers and payers have
substantial purchasing leverage in their dealings with us. The
discovery of significant problems with a product similar to one of
our products that implicate an entire class of products could have
a material adverse effect on sales of the affected products and on
our business and results of operations. Our efforts to acquire
other companies or products and to integrate the operations of
companies we have acquired may not be successful. A breakdown,
cyberattack or information security breach could compromise the
confidentiality, integrity and availability of our systems and our
data. Our stock price is volatile and may be affected by a number
of events. Our business performance could affect or limit the
ability of our Board of Directors to declare a dividend or our
ability to pay a dividend or repurchase our common stock. We may
not be able to access the capital and credit markets on terms that
are favorable to us, or at all.
The scientific information discussed in this news release
related to our product candidates is preliminary and investigative.
Such product candidates are not approved by the U.S. Food and Drug
Administration, and no conclusions can or should be drawn regarding
the safety or effectiveness of the product candidates.
CONTACT: Amgen, Thousand
Oaks
Trish Hawkins, 805-447-5631
(Media)
Arvind Sood, 805-447-1060
(Investors)
References:
- Eisenhauer EA, Therasse P, Bogaerts J, et al. New response
evaluation criteria in solid tumours: Revised RECIST guideline
(version 1.1). European Journal of Cancer.
2009;45:228-247.
- Cox A, et al. Drugging the undruggable RAS: Mission
possible? Nat Rev Drug Discov. 2014
Nov;13(11):828-51.
- Fernandez-Medarde A, Santos E. Ras in Cancer and
Developmental Diseases. Genes Cancer. 2011
Mar;2(3):344-58.
- Lipford, JR. Pre-clinical development of AMG 510: the first
inhibitor of KRASG12C in clinical testing. Oral presentation at
AACR 2019, Atlanta, GA. March 29-April
3, 2019.
- Stephen AG, et al. Dragging ras back in the ring. Cancer
Cell. 2014 Mar 17;25(3):272-81.
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