Results From the PARADIGM Phase 3 Head-to-Head
Trial of Vectibix® (panitumumab) Versus Bevacizumab in
Untreated RAS Wild-Type Metastatic Colorectal Cancer*
Largest Evaluation of Acquired Resistance to
LUMAKRAS®/LUMYKRAS® (sotorasib) in
KRAS G12C-mutated Cancers Inform Combination Treatment
Approaches
THOUSAND
OAKS, Calif., May 26, 2022
/PRNewswire/ -- Amgen (NASDAQ: AMGN) will present new data from
across its broad oncology innovative medicines and biosimilars
portfolio and robust pipeline at the American Society of
Clinical Oncology (ASCO) Annual Meeting from June 3-7 in
Chicago and virtually.
Oral presentations will showcase Amgen's medicines for both lung
and colorectal cancers with a plenary session highlighting the
results from the PARADIGM Phase 3 head-to-head trial conducted by
Takeda Pharmaceutical Company in Japan comparing the efficacy of
Vectibix® (panitumumab) versus Avastin®
(bevacizumab), both used in combination with chemotherapy, in
patients with previously untreated RAS wild-type
metastatic colorectal cancer (mCRC)*. Data from a pooled analysis
of CodeBreaK 100, representing the largest evaluation of mechanisms
of acquired resistance in KRASG12C inhibition, offer new
insights to help inform combination treatment approaches with
LUMAKRAS®/ LUMYKRAS®.
"Amgen continues to lead the science in KRASG12C
inhibition and is committed to advancing research into how LUMAKRAS
can improve outcomes for more patients, including further defining
resistance patterns to guide our robust combination treatment
development program," said David M. Reese, M.D., executive
vice president of Research and Development at Amgen. "In
addition, the compelling head-to-head results further reinforcing
the important role Vectibix plays in the treatment of colorectal
cancer, illustrate how Amgen is expanding the impact of our
first-in-class therapies in some of the most challenging-to-treat
cancers."
In the CodeBreaK 100 analysis, investigators evaluated patterns
of resistance to LUMAKRAS in patients with NSCLC (n=67) and CRC
(n=45) at disease progression. At least one newly acquired genomic
alteration at progression was detected in 19 (28%) NSCLC patients
and in 33 (73%) CRC patients. The alterations were heterogeneous in
both tumor types, with variants detected across multiple genes and
pathways.
Other research highlights being presented on Amgen Oncology's
growing precision medicine and T-cell engager pipeline include
study updates on bemarituzumab, a potential first-in-class therapy
for a subset of gastric and gastroesophageal cancers that
overexpress fibroblast growth factor receptor 2 (FGFR2b), AMG 193,
a small molecule methylthioadenosine (MTA) cooperative protein
arginine methyltransferase 5 (PRMT5) inhibitor being investigated
for the treatment of solid tumors, and tarlatamab, an
investigational, first-in-class half-life extended (HLE) bispecific
T-cell engager (BiTE®) molecule that is uniquely
designed to target delta-like ligand 3 (DLL3) in neuroendocrine
cancers.
Additional information on Amgen's abstracts is available on the
ASCO website.
Abstracts and Presentation Times:
Amgen Sponsored Abstracts
LUMAKRAS®/LUMYKRAS®
(sotorasib)
- Largest evaluation of acquired resistance to sotorasib in
KRAS p.G12C-mutated non-small cell lung cancer (NSCLC) and
colorectal cancer (CRC): plasma biomarker analysis of CodeBreaK
100
Abstract #102, Oral Presentation Session:
Clinical Science Symposium, ctDNA: Dawn of a New
Era, Saturday, June 4 from 8:00-9:30 a.m. CDT
- First data for sotorasib in patients with pancreatic cancer
with KRAS p.G12C mutation: a phase 1/2 study evaluating
efficacy and safety
Abstract #360490, Plenary Series:
Rapid Abstract Updates, Sunday, June
5 from 4:30-6:00 p.m. CDT
- Trial-in-progress: A phase 2 study of sotorasib as
first-line treatment in patients with stage IV non-small cell lung
cancer (NSCLC) whose tumors harbor a KRAS p.G12C
mutation (CodeBreaK 201)
Abstract
#TPS9150, Poster Presentation Session: Lung
Cancer—Non-Small Cell Metastatic, Monday, June 6 from
8:00-11:00 a.m. CDT
IMLYGIC® (talimogene laherparepvec)
- Primary analysis of a phase 2, open-label, multicenter trial
of talimogene laherparepvec (T-VEC) plus pembrolizumab (pembro) for
the treatment (Tx) of patients (pts) with advanced melanoma (MEL)
who progressed on prior anti–PD-1 therapy:
MASTERKEY-115
Abstract #9518, Poster Discussion Session:
Melanoma/Skin Cancers, Monday, June 6
from 4:30-6:00 p.m. CDT
Investigational BiTE® Platform
- Trial-in-progress: Phase 2 study of tarlatamab, a
DLL3-targeting half-life extended bispecific T-cell engager (HLE
BiTE®) immuno-oncology therapy, in relapsed/refractory
small cell lung cancer (SCLC)
Abstract #TPS8603, Poster Presentation Session: Lung
Cancer-Non-small cell local-regional/small cell/other thoracic
cancers, Monday, June 6 from 8:00-11:00 a.m.
CDT
- Trial-in-progress: A phase 1 study of AMG 509 in patients
(pts) with metastatic castration-resistant prostate cancer
(mCRPC)
Abstract #TPS5101, Poster Session: Genitourinary
Cancer—Prostate, Testicular, and Penile, Monday, June
6 from 1:15-4:15 p.m. CDT
AMG 193
- Trial-in-progress: Design and rationale of a phase 1
dose-escalation study of AMG 193, a methylthioadenosine
(MTA)-cooperative PRMT5 inhibitor, in patients with advanced
methylthioadenosine phosphorylase (MTAP)-null solid
tumors
Abstract #TPS3167, Poster Presentation Session:
Developmental Therapeutics—Molecularly Targeted Agents and Tumor
Biology, Sunday, June 5 from 8:00-11:00 a.m. CDT
Bemarituzmab
- Trial-in-progress: Phase 3 study of bemarituzumab +
mFOLOFOX6 versus placebo + mFOLFOX6 in previously untreated
advanced gastric or gastroesophageal junction (GEJ) cancer with
FGFR2b overexpression (FORTITUDE-101)
Abstract
#TPS4164, Poster Presentation: Gastrointestinal
Cancer—Gastroesophageal, Pancreatic, and
Hepatobiliary, Saturday, June 4 from 8:00-11:00 a.m. CDT
- Trial-in-progress: Phase 1b/3
study of bemarituzumab + mFOLFOX6 + nivolumab vs mFOLFOX6 +
nivolumab in previously untreated advanced gastric and
gastroesophageal junction (GEJ) cancer with FGFR2b overexpression
(FORTITUDE-102)
Abstract #TPS4165, Poster Presentation:
Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and
Hepatobiliary, Saturday, June 4 from 8:00-11:00 a.m. CDT
Partner-Led Abstracts
Vectibix® (panitumumab)
- Plasma RAS dynamics and anti-EGFR rechallenge efficacy in
patients with RAS/BRAF wild-type metastatic colorectal
cancer: REMARRY and PURSUIT trials
Abstract
#3518, Poster Discussion Session: Gastrointestinal
Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00
a.m. CDT
- Resistance mechanisms to anti-EGFR therapy in RAS/RAF
wildtype colorectal cancer varies by regimen and line of
therapy
Abstract #3554, Poster Presentation:
Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
- Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV)
plus mFOLFOX6 as first-line treatment in patients with RAS
wild-type metastatic colorectal cancer (mCRC): results from the
phase 3 PARADIGM trial
Abstract #LBA1, Plenary Session:
Primary Track: Special Sessions, Sunday, June 5 from
1:00-4:00 p.m. CDT
Prolia® (denosumab)
- Long-term outcomes of adjuvant denosumab in breast cancer:
Fracture reduction and survival results from 3,425 patients in the
randomised, double-blind, placebo-controlled ABCSG-18
trial
Abstract #507, Oral Presentation: Breast
Cancer—Local/Regional/Adjuvant, Tuesday, June 7 from
9:45 a.m.-12:45 p.m. CDT
Investigator Sponsored Studies (ISS)
IMLYGIC® (talimogene laherparepvec)
- Trial-in-progress: Neo-adjuvant T-VEC plus nivolumab
combination therapy for resectable early- stage or metastatic
(IIIB-IVM1a) melanoma with injectable disease: The NIVEC
trial
Abstract #TPS9607, Poster Session: Melanoma/Skin
Cancers, Monday, June 6 from
1:15-4:15 p.m. CDT
KYPROLIS® (carfilzomib)
- A phase II study of daratumumab with weekly carfilzomib,
pomalidomide, and dexamethasone in relapsed and refractory multiple
myeloma
Abstract #8012, Poster Discussion Session:
Hematologic Malignancies – Plasma Cell Dyscrasia, Saturday, June 4 from 4:30-6:00 p.m. CDT
- ATLAS: A phase 3 randomized trial of carfilzomib,
lenalidomide, and dexamethasone versus lenalidomide alone after
stem-cell transplant for multiple myeloma
Abstract #8001,
Oral Abstract Session: Hematologic Malignancies—Plasma Cell
Dyscrasia, Sunday, June 5 from
8:00-11:00 a.m. CDT
- Daratumumab carfilzomib lenalidomide and dexamethasone as
induction therapy in high-risk, transplant-eligible patients with
newly diagnosed myeloma: Results of the phase 2 study IFM
2018-04
Abstract #8002, Oral Abstract Session:
Hematologic Malignancies—Plasma Cell Dyscrasia, Sunday, June 5 from 8:00-11:00 a.m. CDT
LUMAKRAS®/LUMYKRAS® (sotorasib)
- Trial-in-progress: A phase Ib/II study of sotorasib
combined with chemotherapy for second-line treatment of KRAS
p. G12C mutated advanced pancreatic cancer
Abstract
#TPS4194, Poster Session: Gastrointestinal Cancer—Gastroesophageal,
Pancreatic, and Hepatobiliary, Saturday, June 4 from
8:00-11:00 a.m. CDT
- Predictors of biomarker testing among patients (pts) with
metastatic non-small cell lung cancer (mNSCLC)
Abstract
#9130, Poster Session: Lung Cancer—Non-Small Cell
Metastatic, Monday, June 6 from 8:00-11:00 a.m. CDT
Vectibix® (panitumumab)
- Phase 2 study of anti-EGFR rechallenge therapy with
panitumumab with or without trametinib in advanced colorectal
cancer
Abstract #3520, Poster Discussion
Session: Gastrointestinal Cancer—Colorectal and
Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
- Negative hyperselection for mutations associated with
anti-EGFR antibody resistance in RAS wildtype metastatic
colorectal cancer (mCRC): Evaluation of the PANAMA trial (AIO-KRK-0212, maintenance
therapy with 5-FU, folinic acid (FU/FA) with or without
panitumumab)
Abstract #3536, Poster
Session: Gastrointestinal Cancer—Colorectal and
Anal, Saturday, June 4 from 8:00-11:00
a.m. CDT
- Consensus molecular subtypes (CMS) as prognostic &
predictive biomarkers of panitumumab (Pmab), fluorouracil &
folinic acid (FU/FA) or FU/FA maintenance therapy following
Pmab-FOLFOX induction in RAS wildtype metastatic colorectal
cancer (mCRC) - PANAMA trial
(AIO-KRK-0212)
Abstract #3537, Poster Session:
Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
- Impact of age and gender on the efficacy & safety of
panitumumab plus fluorouracil & folinic acid versus
fluorouracil and folinic acid alone as maintenance therapy in
RAS WT metastatic colorectal cancer (mCRC). Subgroup
analysis of the PANAMA-study
(AIO-KRK-0212)
Abstract #3567, Poster Session:
Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
- Predictive and prognostic value of carcinoembryonic antigen
(CEA) on maintenance therapy with 5-fluoruracil/leucovorin plus
panitumumab or 5-fluoruracil/leucovorin alone in RAS
wildtype metastatic colorectal cancer: Evaluation of the phase II
PanaMa trial (AIO KRK 0212)
Abstract # 3587, Poster Session:
Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
- Modified FOLFOXIRI plus panitumumab (mFOLFOXIRI/PAN) versus
mFOLFOX6/PAN as initial treatment of unresectable RAS and
BRAF wild-type metastatic colorectal cancer (mCRC) patients:
results of the phase III randomized TRIPLETE study by
GONO
Abstract #LBA3505, Oral
Presentation: Gastrointestinal Cancer—Colorectal and Anal,
Saturday, June 4 from 9:45 a.m.–12:45
p.m. CDT
- Randomized intermittent or continuous panitumumab plus
FOLFIRI (FOLFIRI/PANI) for first-line treatment of patients (pts)
with RAS/BRAF wild-type metastatic colorectal cancer (mCRC):
the IMPROVE study
Abstract #3503, Oral Abstract
Session: Gastrointestinal Cancer—Colorectal and Anal, Monday,
June 6 from 9:45 a.m.-12:45 p.m.
CDT
XGEVA® (denosumab)
- Trial-in-progress: A phase 3 study to determine the breast
cancer risk reducing effect of denosumab in women carrying a
germline BRCA1 mutation (BRCA-P Study)
Abstract
#TPS10616, Poster Session: Prevention, Risk Reduction,
and Hereditary Cancer, Monday, June 6 from 1:15-4:15 p.m. CDT
*Amgen out licenses Vectibix to Takeda in Japan.
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 8% 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 Vectibix® (panitumumab)
Vectibix
is the first fully human monoclonal anti-EGFR antibody approved by
the FDA for the treatment of mCRC. Vectibix was approved
in the U.S. in September 2006 as a monotherapy
for the treatment of patients with EGFR-expressing mCRC after
disease progression after prior treatment with fluoropyrimidine-,
oxaliplatin-, and irinotecan-containing chemotherapy.
In May 2014, the FDA approved Vectibix for use in
combination with FOLFOX, as first-line treatment in patients with
wild-type KRAS (exon 2) mCRC. With this approval,
Vectibix became the first-and-only biologic therapy indicated for
use with FOLFOX, one of the most commonly used chemotherapy
regimens, in the first-line treatment of mCRC for patients with
wild-type KRAS mCRC.
In June 2017, the FDA approved a refined
indication for Vectibix for use in in patients with
wild-type RAS (defined as wild-type in
both KRAS and NRAS as determined
by an FDA-approved test for this use) mCRC.
INDICATION AND LIMITATION OF USE
Vectibix® is indicated for the treatment of
patients with wild-type RAS (defined as wild-type
in both KRAS and NRAS as
determined by an FDA-approved test for this use) metastatic
colorectal cancer (mCRC): as first-line therapy in combination
with FOLFOX, and as monotherapy following disease progression after
prior treatment with fluoropyrimidine-, oxaliplatin-, and
irinotecan-containing chemotherapy.
Limitation of Use: Vectibix® is not indicated
for the treatment of patients with RAS mutant mCRC or
for whom RAS mutation status is unknown.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: DERMATOLOGIC TOXICITY
Dermatologic Toxicity: Dermatologic toxicities
occurred in 90% of patients and were severe (NCI-CTC grade 3 and
higher) in 15% of patients receiving Vectibix
monotherapy [see Dosage and Administration (2.3),
Warnings and Precautions (5.1), and Adverse Reactions
(6.1)].
- In Study 20020408, dermatologic toxicities occurred in 90% of
patients and were severe (NCI-CTC grade 3 and higher) in 15% of
patients with mCRC receiving Vectibix®. The clinical
manifestations included, but were not limited to, acneiform
dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia,
dry skin, and skin fissures.
- Monitor patients who develop dermatologic or soft tissue
toxicities while receiving Vectibix® for the
development of inflammatory or infectious sequelae.
Life-threatening and fatal infectious complications including
necrotizing fasciitis, abscesses, and sepsis have been observed in
patients treated with Vectibix®. Life-threatening and
fatal bullous mucocutaneous disease with blisters, erosions, and
skin sloughing has also been observed in patients treated with
Vectibix®. It could not be determined whether these
mucocutaneous adverse reactions were directly related to EGFR
inhibition or to idiosyncratic immune- related effects
(e.g., Stevens Johnson syndrome or toxic epidermal
necrolysis). Withhold or discontinue Vectibix® for
dermatologic or soft tissue toxicity associated with severe or
life-threatening inflammatory or infectious complications. Dose
modifications for Vectibix® concerning dermatologic
toxicity are provided in the product labeling.
- Vectibix® is not indicated for the treatment of
patients with colorectal cancer that harbor
somatic RAS mutations in exon 2 (codons 12 and
13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of
either KRAS or NRAS and hereafter
is referred to as "RAS."
- Retrospective subset analyses across several randomized
clinical trials were conducted to investigate the role
of RAS mutations on the clinical effects of
anti-EGFR-directed monoclonal antibodies (panitumumab or
cetuximab). Anti-EGFR antibodies in patients with tumors
containing RAS mutations resulted in exposing
those patients to anti-EGFR related adverse reactions without
clinical benefit from these agents. Additionally, in Study
20050203, 272 patients with RAS-mutant mCRC tumors
received Vectibix® in combination with FOLFOX and
276 patients received FOLFOX alone. In an exploratory subgroup
analysis, OS was shorter (HR = 1.21, 95% CI: 1.01-1.45)
in patients with RAS-mutant mCRC who received
Vectibix® and FOLFOX versus FOLFOX alone.
- Progressively decreasing serum magnesium levels leading to
severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study
20080763) of patients across clinical trials. Monitor patients for
hypomagnesemia and hypocalcemia prior to initiating
Vectibix® treatment, periodically during
Vectibix® treatment, and for up to 8 weeks after
the completion of treatment. Other electrolyte disturbances,
including hypokalemia, have also been observed. Replete magnesium
and other electrolytes as appropriate.
- In Study 20020408, 4% of patients experienced infusion
reactions and 1% of patients experienced severe infusion reactions
(NCI-CTC grade 3-4). Infusion reactions, manifesting as fever,
chills, dyspnea, bronchospasm, and hypotension, can occur following
Vectibix® administration. Fatal infusion reactions
occurred in postmarketing experience. Terminate the infusion for
severe infusion reactions.
- Severe diarrhea and dehydration, leading to acute renal failure
and other complications, have been observed in patients treated
with Vectibix® in combination with
chemotherapy.
- Fatal and nonfatal cases of interstitial lung disease (ILD)
(1%) and pulmonary fibrosis have been observed in patients treated
with Vectibix®. Pulmonary fibrosis occurred in less than
1% (2/1467) of patients enrolled in clinical studies of
Vectibix®. In the event of acute onset or worsening of
pulmonary symptoms interrupt Vectibix® therapy.
Discontinue Vectibix® therapy if ILD is
confirmed.
- In patients with a history of interstitial pneumonitis or
pulmonary fibrosis, or evidence of interstitial pneumonitis or
pulmonary fibrosis, the benefits of therapy with
Vectibix® versus the risk of pulmonary
complications must be carefully considered.
- Exposure to sunlight can exacerbate dermatologic toxicity.
Advise patients to wear sunscreen and hats and limit sun exposure
while receiving Vectibix®.
- Keratitis and ulcerative keratitis, known risk factors for
corneal perforation, have been reported with
Vectibix® use. Monitor for evidence of keratitis or
ulcerative keratitis. Interrupt or discontinue
Vectibix® for acute or worsening keratitis.
- In an interim analysis of an open-label, multicenter,
randomized clinical trial in the first-line setting in patients
with mCRC, the addition of Vectibix® to the
combination of bevacizumab and chemotherapy resulted in decreased
OS and increased incidence of NCI-CTC grade 3-5 (87% vs 72%)
adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at
a higher rate in Vectibix®-treated patients included
rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%),
dehydration (16% vs 5%), primarily occurring in patients with
diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs <
1%), and hypomagnesemia (4% vs 0).
- NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate
in Vectibix®-treated patients (7% vs 3%) and included
fatal events in three (< 1%) Vectibix®-treated
patients. As a result of the toxicities experienced, patients
randomized to Vectibix®, bevacizumab, and chemotherapy
received a lower mean relative dose intensity of each
chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or
infusional 5-FU) over the first 24 weeks on study compared with
those randomized to bevacizumab and chemotherapy.
- Vectibix® can cause fetal harm when
administered to a pregnant woman. Advise pregnant women and females
of reproductive potential of the potential risk to a fetus. Advise
females of reproductive potential to use effective contraception
during treatment, and for at least 2 months after the last dose of
Vectibix®.
- In monotherapy, the most commonly reported adverse reactions (≥
20%) in patients with Vectibix® were skin rash with
variable presentations, paronychia, fatigue, nausea, and
diarrhea.
- The most commonly reported adverse reactions (≥ 20%) with
Vectibix® + FOLFOX were diarrhea, stomatitis,
mucosal inflammation, asthenia, paronychia, anorexia,
hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus,
and dry skin. The most common serious adverse reactions (≥ 2%
difference between treatment arms) were diarrhea and
dehydration.
To see the Vectibix® Prescribing Information,
including Boxed Warning visit www.vectibix.com.
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
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No forward-looking statement can be guaranteed and actual
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Our results may be affected by our ability to successfully
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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
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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
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of events. Our business and operations may be negatively affected
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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
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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. Further, any
scientific information discussed in this news release relating to
new indications for our products is preliminary and investigative
and is not part of the labeling approved by the U.S. Food and Drug
Administration for the products. The products are not approved for
the investigational use(s) discussed in this news release, and no
conclusions can or should be drawn regarding the safety or
effectiveness of the products for these uses.
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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SOURCE Amgen