THOUSAND OAKS, Calif.,
Oct. 7, 2021 /PRNewswire/
-- Amgen (NASDAQ: AMGN) today announced new combination study
results from the Phase 1b CodeBreaK
101 study, a comprehensive global master protocol trial evaluating
the safety and efficacy of LUMAKRAS™ (sotorasib), the first and
only approved KRASG12C inhibitor, in more than 10
different investigational combination regimens for the treatment of
patients with KRAS G12C-mutated cancers. Results from two
arms of the study — LUMAKRAS with afatinib, a pan-ErbB tyrosine
kinase inhibitor, and LUMAKRAS with trametinib, a mitogen-activated
protein kinase inhibitor (MEKi) — will be presented at the plenary
session titled 'Drugging Difficult Targets' during the
AACR-NCI-EORTC 2021 Virtual International Conference on Molecular
Targets and Cancer Therapeutics on Saturday,
Oct. 9, 2021.
"A critical component of cancer drug development is to
interrogate multiple pathways to understand whether different
combinations can meaningfully advance cancer care. For this reason,
Amgen has undertaken the broadest and most comprehensive global
clinical development program for patients with the KRAS G12C
mutation, exploring multiple combinations that will allow us to
understand where we can best serve patients," said David M. Reese, M.D., executive vice president
of Research and Development at Amgen. "Consistent with our master
protocol clinical trial design, which allows us to rapidly add,
expand or remove cohorts to quickly understand what combinations
work best for patients, Amgen will take these afatinib and
trametinib results into account as we prioritize which combinations
to move forward within our comprehensive LUMAKRAS development
program. We look forward to presenting additional data, including
PD-1 and SHP2 combination datasets,
in the coming months."
LUMAKRAS in Combination with Afatinib (Abstract
LBA6581)
The LUMAKRAS and afatinib combination arm enrolled 33 heavily
pre-treated patients with KRAS G12C-mutated non-small cell
lung cancer (NSCLC), including five patients previously treated
with LUMAKRAS monotherapy. Ten patients received 20 mg of
afatinib/960 mg of sotorasib (cohort 1; 4 patients with prior
LUMAKRAS experience) and 23 patients received 30 mg of afatinib/960
mg of sotorasib (cohort 2; 1 patient with prior LUMAKRAS
experience). The objective response rate (ORR) was 20% in cohort 1
and 35% in cohort 2, and the disease control rate was 70% and 74%
in the two cohorts, respectively.
The most common treatment-related adverse events (TRAEs) for
this study were diarrhea, nausea, and vomiting. TRAEs of grade 3
occurred in 30% of patients in both dose groups with diarrhea being
the most common.
LUMAKRAS in Combination with Trametinib (Abstract
LBA6580)
In CodeBreaK 101, the combination of LUMAKRAS and
trametinib showed antitumor activity in heavily pre-treated
patients with KRAS G12C-mutated solid tumors, including
those with prior KRASG12C inhibitor treatment. A total
of 41 patients were enrolled in the Phase 1b study with 18 patients with NSCLC, 18 patients
with colorectal cancer (CRC) and five patients with other solid
tumors. The maximum tolerated dose tested was 2 mg trametinib/960
mg sotorasib administered daily.
In patients with CRC who were KRASG12C inhibitor
naïve, 9% achieved partial response (1 of 11), and 82% achieved
disease control (9 of 11). In patients who were previously treated
with a KRASG12C inhibitor, 14% achieved partial
response (1 of 7), and 86% achieved disease control (6 of 7).
In patients with NSCLC who were
KRASG12C inhibitor naïve, 20% achieved partial
response (3 of 15) and 87% achieved disease control (13 of 15). In
patients who were previously treated with a KRASG12C
inhibitor, 67% achieved disease control (2 of 3).
The most common TRAEs for this study were diarrhea, rash,
dermatitis acneiform, nausea and vomiting. No new safety concerns
were identified.
About LUMAKRASTM (sotorasib)
Amgen took on
one of the toughest challenges of the last 40 years in cancer
research by developing LUMAKRAS, a
KRASG12C inhibitor.1 LUMAKRAS 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
In May 2021, LUMAKRAS was the
first KRASG12C inhibitor to receive regulatory approval
anywhere in the world with its approval in the U.S., under
accelerated approval. LUMAKRAS is also approved in the United Arab Emirates, and in Canada and Great
Britain under Project Orbis.
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, LUMAKRAS has treated over 3,000 patients
around the world through the clinical development program and
commercial use.
In the U.S., LUMAKRAS was reviewed by the FDA under its
Real-Time Oncology Review (RTOR), a pilot program that aims to
explore a more efficient review process that ensures safe and
effective treatments are made available to patients as early as
possible. Amgen is participating in the FDA's Project Orbis
initiative and through the initiative, has Marketing Authorization
Applications (MAAs) for sotorasib in review in Australia and Brazil. Additionally, Amgen has submitted an
MAA in the European Union, Japan,
Switzerland, South Korea, Singapore, Israel, Turkey, Taiwan, Colombia, Thailand, Mexico and Hong
Kong.
LUMAKRAS is also being studied in multiple other solid
tumors.1
About CodeBreaK
The CodeBreaK clinical development
program for Amgen's 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
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. The Phase 2 trial in
colorectal cancer (CRC) is fully enrolled and results have been
submitted for publication.
A global Phase 3 randomized active-controlled study comparing
sotorasib to docetaxel in patients with KRAS G12C-mutated
NSCLC (CodeBreaK 200) has completed enrollment. Amgen also has
several Phase 1b studies
investigating sotorasib monotherapy and sotorasib combination
therapy across various advanced solid tumors (CodeBreaK 101) open
for enrollment. 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).
For information, please visit www.hcp.codebreaktrials.com.
LUMAKRASTM (sotorasib) U.S.
Indication
LUMAKRASTM 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 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 LUMAKRASTM 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.
For more information, visit www.amgen.com and follow
us on www.twitter.com/amgen.
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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:
- Hong DS, et al. N Engl J
Med. 2020;383:1207-1217.
- Skoulidis F, Li BT, Dy GK, et al. N Engl J Med.
2021;384(25):2371-2381. doi:10.1056/NEJMoa2103695.
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