THOUSAND OAKS, Calif.,
Sept. 8, 2021 /PRNewswire/
-- Amgen (NASDAQ: AMGN) today announced results from two
analyses of the Phase 2 CodeBreaK 100 clinical trial evaluating
LUMAKRAS™ (sotorasib), the first and only
KRASG12C inhibitor approved in the U.S., in the
treatment of previously treated patients with advanced or
metastatic KRAS G12C-mutated non-small cell lung cancer
(NSCLC). These new analyses, respectively, provide encouraging
evidence of durable systemic anticancer activity in patients with
previously treated, stable brain metastases with LUMAKRAS, as well
as insights into biomarkers of LUMAKRAS response. Together with a
poster describing a recently initiated clinical study of the
investigational half-life extended (HLE) bispecific T cell engager
(BiTE®) molecule acapatamab (formerly AMG 160) in
patients with NSCLC, these data are being featured during the
virtual 2021 World Conference on Lung Cancer (WCLC21) hosted by the
International Association for the Study of Lung Cancer (IASLC).
"Amgen is expanding the reach, impact and potential of our
innovative therapies to personalize care for patients with
historically difficult-to-treat cancers like lung cancer," said
David M. Reese, M.D., executive vice
president of Research and Development at Amgen. "We are pleased to
present additional analyses for LUMAKRAS, our newly approved
KRASG12C inhibitor, as well as a trial-in-progress
poster for acapatamab, our investigational BiTE molecule being
studied in NSCLC and other solid tumors. Of the data presented at
WCLC, we are particularly encouraged by the first evaluation of
LUMAKRAS' ability to maintain stabilization of brain metastases in
patients with previously treated, stable brain metastases. We look
forward to the results from our CodeBreaK 101 study where we are
studying a cohort of KRAS G12C-mutated NSCLC patients with
untreated, active brain metastases to better understand the
clinical benefit of LUMAKRAS."
New Analyses From the LUMAKRAS Phase 2 CodeBreaK 100 Clinical
Trial
In a post-hoc analysis (WCLC21 Poster 52.03) of 40
patients (23% of 174 trial participants) with KRAS
G12C-mutated advanced NSCLC who had stable, previously treated
brain metastases at their enrollment in the CodeBreaK 100 trial,
LUMAKRAS achieved a 77.5% disease control rate (DCR), a median
progression-free survival (PFS) of 5.3 months and a median overall
survival (OS) of 8.3 months. This DCR was similar to patients
without brain metastases. In patients evaluable by Response
Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria,
14 of 16 patients (88%) maintained intracranial disease control of
their stable brain lesions during LUMAKRAS therapy with two
achieving complete responses of non-target lesions. The safety
profile of LUMAKRAS in the brain metastases group was consistent
with previous reports. Amgen is enrolling patients with active
brain metastases in an arm of the CodeBreaK 101 study
(NCT04185883).
"Up to 40% of patients with KRAS G12C-mutated
NSCLC may develop brain metastases.1 Given the
overall poor prognosis for this patient subset, there is an urgent
need for novel treatment options,"2 said lead author
Suresh S. Ramalingam, M.D.,
executive director of Winship Cancer Institute of Emory University in Atlanta. "Our results demonstrate the
potential of sotorasib to provide meaningful clinical benefit
for KRAS G12C-mutated NSCLC in the brain."
An additional exploratory descriptive analysis of CodeBreaK 100
being presented during a Mini Oral Presentation (MA14.03) examined
whether the mutation profile of the tumors, in addition to
KRASG12C, is correlated with patients' responses or
resistance to LUMAKRAS. An analysis of baseline tumor samples from
65 patients revealed no single genetic signature that predicted
LUMAKRAS responses and ongoing evaluations will be needed to
further identify potential targetable mechanisms of resistance.
However, the KEAP1 mutation, a known driver of poor clinical
outcomes, was observed in 7 of 22 patients with early progression
and PFS of less than 3 months.
"The introduction of sotorasib ushered in a new standard of care
for patients with KRAS G12C-mutated NSCLC," said lead author
Ferdinandos Skoulidis, M.D., Ph.D., assistant professor of
Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center.
"These biomarker data provide direction for continued research into
characterizing mutation profiles associated with sotorasib
treatment response to help guide clinical practice and inform
innovative combination approaches to overcome potential mechanisms
of resistance."
Advancing BiTE Molecule Acapatamab in NSCLC
In
addition to the LUMAKRAS data, a trial-in-progress abstract
outlined the design of an ongoing open-label, Phase 1b study (NCT04822298) evaluating the safety and
tolerability of acapatamab, a half-life extended BiTE
immuno-oncology therapy that targets prostate specific membrane
antigen (PSMA)-expressing cancer cells in adults with
relapsed/refractory NSCLC. The encouraging benefit-risk profile of
acapatamab in an ongoing trial of patients with metastatic
castration-resistant prostate cancer (mCRPC) (NCT03792841)
suggested its potential for patients with NSCLC, as up to 49 to 85%
of the endothelial cells in a tumor's newly grown blood supply
express PSMA.3,4 Acapatamab engages PSMA on cancer cells
and CD3 on T cells, inducing T-cell activation, proliferation and
target cell lysis to prompt a cancer-fighting immune
response.5
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.6 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.7
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.
Amgen is progressing the largest and broadest global
KRASG12C 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 almost 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 submitted Marketing
Authorization Applications (MAAs) for sotorasib in Australia, Brazil, Canada and the United Kingdom. Additionally, Amgen has
submitted an MAA in the EU and New Drug Applications in
Japan (J-NDA), Switzerland, South
Korea, Singapore,
Israel, Turkey and Taiwan.
LUMAKRAS is also being studied in multiple other solid
tumors.6
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 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.8 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.9
KRAS G12C is the most common KRAS mutation in
NSCLC.10 In the U.S., about 13% of patients with
non-squamous NSCLC harbor the KRAS G12C
mutation.11 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 current therapies
are suboptimal with a median progression-free survival of
approximately 4 months following second-line treatment of
KRAS G12C-mutated NSCLC.12
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. As the most advanced KRAS G12C
clinical development program, CodeBreaK has enrolled more than 800
patients across 13 tumor types since its inception.
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.
About BiTE® Technology
BiTE®
(bispecific T cell engager) technology is a targeted
immuno-oncology platform that is designed to engage a patient's own
T cells to any tumor-specific antigen, activating the cytotoxic
potential of T cells to eliminate detectable cancer. The BiTE
immuno-oncology platform has the potential to treat different tumor
types through tumor-specific antigens. The BiTE platform has a goal
of leading to off-the-shelf solutions, which have the potential to
make innovative T cell treatment available to all providers when
their patients need it. Amgen is advancing BiTE molecules across a
broad range of hematologic malignancies and solid tumors and
further investigating BiTE technology with the goal of enhancing
patient experience and therapeutic potential.
About Acapatamab (formerly AMG 160)
Acapatamab is a
half-life extended (HLE) BiTE immune-oncology therapy that targets
PSMA-expressing cancer cells being investigated in prostate
cancer and non-small cell lung cancer (NSCLC).
Simultaneously binding to PSMA on tumor cells and CD3 on T
cells, acapatamab is designed to engage patients' own T cells to
fight cancer. In an ongoing Phase I, first-in-human study in
patients with metastatic castration-resistant prostate cancer
(mCRPC), acapatamab has demonstrated a manageable safety profile
and promising efficacy as monotherapy.3
The mCRPC study is also examining acapatamab in combination with
pembrolizumab. A Phase 1/2, master protocol study is investigating
the safety, tolerability, dosing and efficacy of acapatamab, in
combination with enzalutamide, abiraterone, or the PD-1 inhibitor
AMG 404 in patients with earlier-line mCRPC. An ongoing open-label,
Phase 1b study is evaluating the
safety and tolerability of acapatamab in adults with
relapsed/refractory NSCLC.
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.
Forward-Looking Statements
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forward-looking statements that are based on the current
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CONTACT: Amgen, Thousand Oaks
Trish Rowland, 805-447-5631
(media)
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