Long-Term Clinical Benefit and Prolonged Tumor
Response Seen With 40.7% Objective Response Rate
No New Safety Signals Observed
Longest Follow-Up of Patients Treated With a
KRASG12C Inhibitor
THOUSAND
OAKS, Calif., April 10,
2022 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today
announced the presentation of long-term efficacy and safety data
from the CodeBreaK 100 Phase 1/2 trial in patients with KRAS
G12C-mutated advanced non-small cell lung cancer (NSCLC) who
received LUMAKRAS® (sotorasib)*. The two-year follow-up
data will be presented orally as part of a clinical trials plenary
session at the American Association for Cancer Research (AACR)
annual meeting on April 10, 2022.
LUMAKRAS is the first and only KRASG12C inhibitor
to-date to show long-term clinical benefit and overall survival in
patients with NSCLC harboring the KRAS G12C mutation.
"With regulatory approvals in nearly 40 countries and thousands
of patients treated, LUMAKRAS, the only approved
KRASG12C inhibitor, is a transformative targeted therapy
for the treatment of patients living with KRAS G12C-mutated
NSCLC," said David M. Reese, M.D.,
executive vice president of Research and Development at Amgen.
"We are pleased with these latest results from the CodeBreaK 100
study, which represent the longest follow-up of patients treated
with a KRASG12C inhibitor and confirm rapid, deep and
durable responses in patients receiving LUMAKRAS."
In this long-term, two-year analysis of 174 heavily pre-treated
patients (172 with baseline measurable lesion(s)), LUMAKRAS
demonstrated a centrally confirmed objective response rate (ORR) of
40.7%, disease control rate (DCR) of 83.7% and median duration of
response (DOR) of 12.3 months. Five patients achieved complete
responses and 65 patients achieved partial responses. The results
also showed median progression-free survival (PFS) of 6.3 months
and overall survival (OS) of 12.5 months with 32.5% of patients
still alive at two years. No new safety signals for LUMAKRAS were
identified with the long-term follow-up.
"Since the FDA approval almost a year ago, LUMAKRAS has changed
the treatment paradigm for patients with advanced non-small cell
lung cancer who harbor the KRAS G12C mutation," said
Grace Dy, M.D., chief, thoracic
oncology, Roswell Park Comprehensive Cancer Center. "The durable
efficacy and positive benefit-risk profile seen in the two-year
analysis of CodeBreaK 100 highlight the important role this
innovative targeted therapy can offer long-term."
In May 2021, LUMAKRAS was the
first KRASG12C inhibitor to receive regulatory approval
with its approval in the U.S., under accelerated approval. LUMAKRAS
is now approved in 39 countries.
*LUMAKRAS is marketed as LUMYKRAS® (sotorasib) in the
European Union, the United Kingdom
and Switzerland.
About
LUMAKRAS®/LUMYKRAS® (sotorasib)
Amgen took
on one of the toughest challenges of the last 40 years in cancer
research by developing LUMAKRAS/LUMYKRAS, a
KRASG12C inhibitor.1 LUMAKRAS/LUMYKRAS
has demonstrated a positive benefit-risk profile with rapid, deep,
and durable anticancer activity in patients with locally advanced
or metastatic non-small cell lung cancer (NSCLC) harboring
the KRAS G12C mutation with a once daily oral
formulation.2
Amgen is progressing the largest and broadest global
KRASG12C inhibitor development program with
unparalleled speed and exploring more than 10 sotorasib combination
regimens, including triplets, with clinical trial sites spanning
five continents. To date, over 4,000 patients around the world have
received LUMAKRAS/LUMYKRAS through the clinical development program
and commercial use.
In May 2021, LUMAKRAS was the
first KRASG12C inhibitor to receive regulatory
approval with its approval in the U.S., under accelerated approval.
LUMAKRAS/LUMYKRAS is also approved in the European Union,
Japan, United Arab Emirates, South Korea and Switzerland and in Australia, Brazil, Canada, and Great
Britain under the FDA's Project Orbis. Through Project
Orbis, Amgen also has Marketing Authorization Applications (MAAs)
for sotorasib in review in Israel
and Singapore.
Additionally, Amgen has submitted MAAs in Argentina, Colombia, Hong
Kong, Kuwait, Malaysia, Mexico, Qatar, Saudi
Arabia, Taiwan,
Thailand and Turkey.
LUMAKRAS/LUMYKRAS is also being studied in multiple other solid
tumors.3
About Non-Small Cell Lung Cancer and
the KRAS G12C Mutation
Lung cancer is the
leading cause of cancer-related deaths worldwide, and it accounts
for more deaths worldwide than colon cancer, breast cancer and
prostate cancer combined.4 Overall survival rates for
NSCLC are improving but remain poor for patients with advanced
disease and 5-year survival is only 7% for those with
metastatic disease.5
KRAS G12C is the most
common KRAS mutation in
NSCLC.6 About 13% of patients with NSCLC harbor
the KRAS G12C mutation.7 Unmet
medical need remains high and treatment options are limited for
NSCLC patients with the KRAS G12C mutation whose
first-line treatment has failed to work or has stopped working. The
outcomes with other approved therapies are suboptimal, with a
median progression-free survival of approximately four months
following second-line treatment
of KRAS G12C-mutated NSCLC.8
About CodeBreaK
The CodeBreaK clinical development
program for Amgen's drug sotorasib is designed to study
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.9
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 2 study was centrally
assessed objective response rate. The Phase 2 trial in NSCLC
enrolled 126 patients, 124 of whom had centrally evaluable lesions
by RECIST at baseline.2 The Phase 2 trial in colorectal
cancer (CRC) is fully enrolled and results have been
published.10
CodeBreaK 200, the global Phase 3 randomized active-controlled
study comparing sotorasib to docetaxel in
KRAS G12C-mutated NSCLC completed enrollment of 345
patients. Eligible patients had previously treated, locally
advanced and unresectable or metastatic
KRAS G12C-mutated NSCLC. The primary endpoint is
progression-free survival and key secondary endpoints include
overall survival, objective response rate, and patient-reported
outcomes.11
Amgen also has several Phase 1b studies investigating sotorasib monotherapy
and sotorasib combination therapy across various advanced solid
tumors (CodeBreaK 101) open for enrollment.12 A Phase 2
randomized study will evaluate sotorasib in patients with stage
IV KRAS G12C-mutated NSCLC in need of first-line
treatment (CodeBreaK 201).13
For information, please
visit www.hcp.codebreaktrials.com.
LUMAKRAS® (sotorasib) U.S. Indication
LUMAKRAS is indicated for the treatment of adult patients
with KRAS G12C-mutated locally advanced or
metastatic non-small cell lung cancer (NSCLC), as determined by an
FDA-approved test, who have received at least one prior systemic
therapy.
This indication is approved under accelerated approval based on
overall response rate (ORR) and duration of response (DOR).
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in a confirmatory
trial(s).
LUMAKRAS® (sotorasib) Important U.S. Safety
Information
Hepatotoxicity
- LUMAKRAS can cause hepatotoxicity, which may lead to
drug-induced liver injury and hepatitis.
- Among 357 patients who received LUMAKRAS in CodeBreaK 100,
hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A
total of 18% of patients who received LUMAKRAS had increased
alanine aminotransferase (ALT)/increased aspartate aminotransferase
(AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose
interruption or reduction, 5% of patients received corticosteroids
for the treatment of hepatotoxicity.
- Monitor liver function tests (ALT, AST and total bilirubin)
prior to the start of LUMAKRAS every 3 weeks for the first 3 months
of treatment, then once a month or as clinically indicated, with
more frequent testing in patients who develop transaminase and/or
bilirubin elevations.
- Withhold, dose reduce or permanently discontinue LUMAKRAS based
on severity of adverse reaction.
Interstitial Lung Disease (ILD)/Pneumonitis
- LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357
patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis
occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset,
and 1 case was fatal. LUMAKRAS was discontinued due to
ILD/pneumonitis in 0.6% of patients.
- Monitor patients for new or worsening pulmonary symptoms
indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever).
Immediately withhold LUMAKRAS in patients with suspected
ILD/pneumonitis and permanently discontinue LUMAKRAS if no other
potential causes of ILD/pneumonitis are identified.
Most Common Adverse Reactions
- The most common adverse reactions ≥ 20% were diarrhea,
musculoskeletal pain, nausea, fatigue, hepatotoxicity and
cough.
Drug Interactions
- Advise patients to inform their healthcare provider of all
concomitant medications, including prescription medicines,
over-the-counter drugs, vitamins, dietary and herbal products.
- Inform patients to avoid proton pump inhibitors and
H2 receptor antagonists while taking LUMAKRAS.
- If coadministration with an acid-reducing agent cannot be
avoided, inform patients to take LUMAKRAS 4 hours before or 10
hours after a locally acting antacid.
Please see LUMAKRAS full Prescribing
Information.
About Amgen Oncology
At Amgen Oncology,
our mission to serve patients drives all that we do. That's why
we're relentlessly focused on accelerating the delivery of
medicines that have the potential to empower all angles of care and
transform lives of people with cancer.
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're advancing oncology at the speed of
life™.
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.
Amgen is one of the 30 companies that comprise the Dow
Jones Industrial Average and is also part of the Nasdaq-100 index.
In 2021, Amgen was named one of the 25 World's Best
Workplaces™ by Fortune and Great Place to Work™ and one
of the 100 most sustainable companies in the world
by Barron's.
For more information, visit www.amgen.com and follow
us on www.twitter.com/amgen.
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CONTACT: Amgen, Thousand Oaks
Megan Fox, 805-447-1423 (media)
Jessica Akopyan, 805-440-5721
(media)
Arvind Sood, 805-447-1060
(investors)
LUMAKRAS, LUMYKRAS, Otezla, and Advancing Oncology at The
Speed of Life are trademarks of Amgen Inc.
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https://clinicaltrials.gov/ct2/show/NCT04303780 . Accessed on
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12 ClinicalTrials.gov. CodeBreaK 101. Available at:
https://clinicaltrials.gov/ct2/show/NCT04185883 . Accessed on
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13 ClinicalTrials.gov. CodeBreaK 201. Available at:
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