THOUSAND OAKS, Calif.,
Sept. 20, 2020 /PRNewswire/ --
Amgen (NASDAQ: AMGN) today announced that updated data from
the full Phase 1 cohort of the CodeBreaK 100 clinical study,
evaluating sotorasib (proposed INN for AMG 510) in 129 patients
across multiple advanced solid tumors, were published in the New
England Journal of Medicine (NEJM). Data from 59 patients with
advanced non-small cell lung cancer reported in the NEJM manuscript
were also featured today during an oral presentation at ESMO
2020.
"CodeBreaK 100 is the largest Phase 1/2, and first-in-human,
clinical study for a KRASG12C inhibitor," said
David M. Reese, M.D., executive vice
president of Research and Development at Amgen. "Earlier this year
at ASCO, we reported encouraging early data in patients with
advanced colorectal cancer and a number of other solid tumors.
We're pleased to share these updated Phase 1 results, particularly
in patients with advanced non-small cell lung cancer, and look
forward to the Phase 2 readout in this heavily pretreated
population later this year."
Sotorasib demonstrated confirmed objective response rate (ORR)
and disease control rates (DCR) of 35.3% and 91.2%, respectively,
in 34 heavily pretreated patients (median of two prior lines of
therapy) with NSCLC, who were treated with the 960 mg daily dose
(data cutoff of June 1, 2020).
Anticancer activity was seen across all dose levels in patients
with NSCLC, with a confirmed ORR of 32.2% and DCR of 88.1%, and
median duration of response of 10.9 months, with 10 of 19
responders still in response as of the data cutoff.
Tumor shrinkage was observed in 71.2% of patients at the first
week-6 assessment. Median progression-free survival (mPFS) in
patients treated with sotorasib was 6.3 months.
Safety and tolerability in patients with NSCLC were consistent
with previously seen CodeBreaK 100 results. No dose-limiting
toxicities were observed and there were no fatal treatment-related
adverse events (TRAEs). The most common TRAEs were diarrhea
(25.4%), alanine aminotransferase (ALT) increase (20.3%), aspartate
aminotransferase (AST) increase (20.3%), fatigue (10.2%) and nausea
(10.2%). Eleven (18.6%) patients had grade 3 or higher TRAEs, one
of whom had grade 3 TRAEs of ALT and AST increases that led to
discontinuation of treatment.
"These latest results show that sotorasib continues to
demonstrate encouraging clinical benefit in heavily pretreated
patients with KRAS G12C-mutant tumors," said lead author
David S. Hong, M.D., Department of
Investigational Cancer Therapeutics, Division of Cancer Medicine,
The University of Texas MD Anderson
Cancer Center, TX. "The results
also establish a compelling trend in tumor shrinkage and median
progression-free survival with a positive benefit-risk
profile."
The ESMO oral presentation included Phase 1 NSCLC results
published in NEJM, as well as data on potential biomarkers
of response to sotorasib that demonstrated clinical activity across
a range of KRAS G12C mutant allele frequencies (MAFs), PD-L1
tissues expression levels, tumor mutational burden (TMB) plasma
levels and tissue co-mutational profiles.
"KRAS G12C is a driver of multiple solid tumor types and
is particularly prevalent in non-small cell lung cancer," said
Fabrice Barlesi, M.D., Ph.D.,
Professor of Medicine at Aix-Marseille University, Medical Director
of Gustave Roussy Institute, Paris,
France. "Despite this, there are currently no approved
targeted therapy options for KRAS G12C and patients remain
in need of additional treatment options, which makes these new
findings particularly important."
Amgen Webcast Investor Call
Amgen will host two
webcast calls for the investment community in conjunction with the
ESMO Virtual Congress 2020. On Sunday, Sept. 20, 2020, at 11:00
a.m. PDT, David M. Reese, M.D., executive vice president of
Research and Development at Amgen, along with members of Amgen's
clinical development team and clinical investigators, will discuss
Phase 1 data being presented on the Company's investigational
KRASG12C inhibitor sotorasib (AMG 510). On Monday, Sept. 21, at 1:00
p.m. PDT, David M. Reese,
M.D., along with members of Amgen's clinical development team, will
discuss the Phase 1 data being presented on the Company's
investigational half-life extended bispecific T-cell engager
(BiTE®) immuno-oncology therapy targeting
prostate-specific membrane antigen (PSMA).
Live audio of the conference call will be broadcast over the
internet simultaneously and will be available to members of the
news media, investors and the general public.
The webcast, as with other selected presentations regarding
developments in Amgen's business given at certain investor and
medical conferences, can be accessed on Amgen's
website, www.amgen.com, under Investors. Information regarding
presentation times, webcast availability and webcast links are
noted on Amgen's Investor Relations Events Calendar. The
webcast will be archived and available for replay for at least 90
days after the event.
About KRAS
The RAS gene family, which
has been the subject of almost four decades of research, contains
some of the most frequently mutated oncogenes in human
cancers.1,2 Targeting the KRAS protein, the most
commonly altered family member in solid tumors, has been one of the
toughest challenges in cancer research.1 A specific
mutation known as KRAS G12C, is a major driver of tumor
growth, occurring broadly across solid tumor indications. In the
U.S., about 13% of patients with non-small cell lung cancer harbor
the KRAS G12C mutation.3,4 It is also
found in approximately 3-5% of colorectal cancers and 1-2% of
numerous other solid tumors, making this among the most broadly
represented mutations across cancer patient
subgroups.5,6,7,8,9. With the discovery of a
unique surface groove in the KRASG12C protein, Amgen
developed and advanced the first investigational
KRASG12C inhibitor into the clinic and is exploring the
potential of KRASG12C inhibition across multiple
tumor types for patients who remain in dire need of treatment
options.1,10
About CodeBreaK
The CodeBreaK clinical trial program
for Amgen's investigational drug sotorasib is designed to treat
patients with an advanced solid tumor with the KRAS G12C
mutation and address the longstanding unmet medical need for these
cancers.
CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label
multicenter study, enrolled patients with KRAS G12C-mutant
solid tumors. Eligible patients must have received a prior line of
systemic anticancer therapy, consistent with their tumor type and
stage of disease. The primary endpoint for the Phase 1 study is
safety, and key secondary endpoints include 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.
Amgen's single-arm Phase 2 trials in both non-small cell lung
cancer (NSCLC) and colorectal cancer (CRC) (also part of CodeBreaK
100) are now fully enrolled. The potentially registrational
Phase 2 trial in NSCLC is on track for data readout later in 2020
and a global Phase 3 randomized active-controlled confirmatory
study comparing sotorasib to docetaxel in NSCLC
(CodeBreaK 200) has begun recruiting. The Phase 2 CRC trial is expected to have a data readout in
2021. Amgen is also currently enrolling six Phase 1b combination studies across various advanced
solid tumors (CodeBreaK 101).
Additional information about CodeBreaK clinical trials can be
found at http://www.codebreaktrials.com.
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.
To learn more about Amgen's innovative pipeline with diverse
modalities and genetically validated targets, please visit
AmgenOncology.com. 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 any statements on the
outcome, benefits and synergies of collaborations, or potential
collaborations, with any other company, including BeiGene Ltd. or
any collaboration or potential collaboration in pursuit of
therapeutic antibodies against COVID-19 (including statements
regarding such collaboration's, or our own, ability to discover and
develop fully-human neutralizing antibodies targeting
SARS-CoV-2 or antibodies against targets other than the
SARS-CoV-2 receptor binding domain, and/or to produce any such
antibodies to potentially prevent or treat COVID-19), or the
Otezla® (apremilast) acquisition (including anticipated
Otezla sales growth and the timing of non-GAAP EPS accretion), as
well as 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, effects of pandemics or
other widespread health problems such as the ongoing COVID-19
pandemic on our business, outcomes, progress, or effects relating
to studies of Otezla as a potential treatment for COVID-19, 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. An outbreak
of disease or similar public health threat, such as COVID-19, and
the public and governmental effort to mitigate against the spread
of such disease, could have a significant adverse effect on the
supply of materials for our manufacturing activities, the
distribution of our products, the commercialization of our product
candidates, and our clinical trial operations, and any such events
may have a material adverse effect on our product development,
product sales, business and results of operations. 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 collaborate with or acquire
other companies, products or technology, and to integrate the
operations of companies or to support the products or technology 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 Rowland, 805-447-5631
(media)
Jessica Akopyan, 805-447-0974
(media)
Arvind Sood, 805-447-1060
(investors)
References
1 Cox AD, et al. Nat Rev Drug Discov.
2014;13:828-851.
2 Fernandez-Medarde A, et al. Genes Cancer.
2011;2:344-358.
3 Biernacka A, et al. Cancer Genet.
2016;209:195-198.
4 Stephen AG, et al. Cancer Cell.
2014;25:272-281.
5 Neumann J, et al. Pathol Res Pract.
2009;205:858-862.
6 Jones RP, et al. Br J Cancer.
2017;116:923-929.
7 Wiesweg M, et al. Oncogene.
2019;38:2953-2966.
8 Canon J, et al. Nature. 2019;575:217-223.
9 Zhou L, et al. Med Oncol. 2016;33:32.
10 Ryan MB, et al. Nat Rev Clin Oncol. 2018;15:709-720.
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