THOUSAND OAKS, Calif.,
May 29, 2020 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced new data from the CodeBreaK 100
clinical development program evaluating investigational AMG 510
(proposed INN sotorasib) in heavily pretreated patients with a
range of KRAS G12C-mutant solid tumors. Updated Phase 1 data
from patients with advanced colorectal cancer (CRC) and other
selected solid tumors continued to demonstrate disease control
activity, safety and tolerability. These data are being presented
during the ASCO20 Virtual Scientific Program, May 29 – 31, 2020.
"Targeting KRAS has been a 40-year quest leaving
patients with limited treatment options. In just under two years in
the clinic, we have seen encouraging early efficacy and safety
data across a number of solid tumors," said David M. Reese, M.D., executive vice president
of Research and Development at Amgen. "New Phase 1 data at ASCO
show that, in some patients with advanced colorectal cancer,
sotorasib monotherapy provided prolonged disease control. A Phase 2
monotherapy study in advanced colorectal cancer has fully enrolled
and will provide further insights into the potential utility of
sotorasib in this disease."
Sotorasib Activity in Patients With Advanced Colorectal
Cancer
CRC is the second leading cause of cancer deaths
worldwide.1 It is the third most commonly diagnosed
cancer globally and incidence is expected to grow by more than 20%
over the next decade.2 For patients with previously
treated metastatic CRC receiving standard therapies, unmet need
remains high, with median progression-free survival (PFS) of about
2 months and response rates of less than 2%.3,4
This Phase 1 dose escalation study evaluated 42 heavily
pretreated patients with advanced KRAS G12C-mutant CRC (data
cut-off of Jan. 2020). All patients
received prior systemic therapies (median of three prior lines),
with 69% having received three or more prior lines of therapy.
Twenty-two (52.4%) and eight (19.0%) patients remained on treatment
for more than three and six months, respectively.
In the 960 mg once-daily target dose cohort, the objective
response rate (ORR) was 12% (3/25) and the disease control rate
(DCR) was 80% (20/25). Median PFS was 4.2 months and overall
survival (OS) had not been reached after a median follow-up of
almost 8 months. Tumor shrinkage was observed in 11 of 23
patients with available post-baseline tumor data.
Across all dose levels, the majority of patients achieved
disease control, with an ORR of 7.1% and a DCR of 76.2%. Disease
stability was maintained for a median of 4.2 months. Median PFS was
4.0 months and median OS was 10.1 months. Tumor shrinkage was
observed in 18 of 39 patients with available post-baseline tumor
data across all doses.
"There is currently a tremendous treatment gap for patients with
advanced KRAS G12C-mutant colorectal cancer," said
Marwan G. Fakih, M.D., primary study
investigator and co-director of the Gastrointestinal Cancer
Program, City of Hope, Duarte, California. "These latest
sotorasib data continue to show encouraging antitumor activity and
tolerability in a patient population that has few treatment
options."
Disease progression was the most common reason for treatment
discontinuation. 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.
Sotorasib Activity in Patients With Advanced Solid
Tumors Other Than NSCLC or CRC
Data were evaluated for 25
heavily pretreated patients with advanced KRAS G12C-mutant
solid tumors other than CRC or NSCLC. These patients had received a
median three prior lines of therapy with a median follow-up of 4.3
months.
These data demonstrated early evidence of a consistent safety
profile and anticancer activity across a range of advanced KRAS
G12C-mutant solid tumors, including pancreatic, appendiceal and
endometrial cancer. Partial responses were confirmed in three
patients with appendiceal, melanoma and endometrial cancer,
respectively. Six of eight evaluable patients with pancreatic
cancer achieved stable disease, and three had approximately a 30%
reduction in tumor burden from baseline. Tumor shrinkage was
observed in 13 of 19 evaluable patients with available
post-baseline tumor data across all tumor types.
A complete listing of Amgen posters is available on the ASCO
website at www.asco.org.
About KRAS
The subject of almost four
decades of research, the RAS gene family contains
the most frequently mutated oncogenes in human
cancers.5,6 Within this family, KRAS is
the most prevalent variant and is particularly common in solid
tumors.5 A specific mutation known as KRAS
G12C is found in approximately 13% of non-small cell lung
cancers, 3% to 5% of colorectal cancers and 1% to 2% of numerous
other solid tumors.7-9 The KRASG12C
protein 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 solid
tumor types.
About CodeBreaK
The CodeBreaK clinical trial program
for Amgen's investigational drug sotorasib is designed to treat
patients with multiple KRAS G12C-mutant solid tumors 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 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 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 in 2020. The
Phase 2 CRC trial is expected to have
a data readout in early 2021.
Amgen is currently enrolling six Phase 1b combination studies across various advanced
solid tumors (CodeBreaK 101). In addition, a randomized global
Phase 3 confirmatory study in NSCLC (CodeBreaK 200) has been
initiated. 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.
Amgen Forward-Looking Statements
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contains forward-looking statements that are based on the current
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Biotechnologies (including statements regarding such
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neutralizing antibodies targeting SARS-CoV-2 to potentially prevent
or treat COVID-19), BeiGene, Ltd., or the Otezla®
(apremilast) acquisition, including anticipated Otezla®
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estimates of revenues, operating margins, capital expenditures,
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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,
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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 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
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CONTACT: Amgen, Thousand Oaks
Trish Rowland, 805-447-5631
(media)
Megan Fox, 805-447-1423 (media)
Arvind Sood, 805-447-1060
(investors)
References
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2018;68:394-424.
2 Arnold, M, et al. Gut.
2017;66:683–691.
3 Mayer RJ, et al. N Engl J Med.
2015;372:1909-1919.
4 Grothey A, et al.
Lancet. 2013;381:303-312.
5 Cox AD, et al. Nat Rev Drug Discov.
2014;13:828-851.
6 Fernandez-Medarde A, et al. Genes
Cancer. 2011;2:344-358.
7 Biernacka A, et al. Cancer Genet.
2016;209:195-198.
8 Neumann J, et al. Pathol Res Pract.
2009;205:858-862.
9 Zhou L, et al. Med
Oncol. 2016;33:32.
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