THOUSAND OAKS, Calif.,
Sept. 17, 2019 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced that new data from its
oncology pipeline and marketed product portfolio will be presented
at the European Society for Medical Oncology (ESMO) 2019
Congress in Barcelona, Spain,
Sept. 27-Oct. 1, 2019.
Clinical data presentations will include a poster discussion on
the ongoing Phase 1 trial of AMG 510, highlighting responses in
KRAS G12C-mutant solid tumors, including patients with
advanced non-small cell lung, colorectal and appendiceal cancers.
AMG 510 is the first KRASG12C inhibitor to reach the
clinical stage in patients with locally advanced or metastatic
KRAS G12C-mutated solid tumors.
Data showing the two-year results of a Phase 2 trial in patients
with neoadjuvant melanoma being treated with IMLYGIC®
(talimogene laherparepvec) plus surgery versus immediate surgery
will be presented as a late-breaking abstract in an oral
presentation. A second late-breaking abstract featuring IMLYGIC
will be presented in a poster discussion session, highlighting
three-year follow-up data of a Phase 2 trial with IMLYGIC in
combination with YERVOY® (ipilimumab) for advanced
melanoma.
"The data being presented at ESMO demonstrate how Amgen is
advancing the next frontier of innovation in the treatment of
cancers," said David M. Reese, M.D.,
executive vice president of Research and Development at Amgen. "In
addition to the responses seen in non-small cell lung cancer
patients with KRAS G12C-mutant tumors, we will report the
first responses in advanced colorectal and appendiceal cancers at
the upcoming congress."
A complete listing of abstracts can be found on the ESMO
website. Notable abstracts of interest include:
Oncology Pipeline
- Phase 1 Study of AMG 510, a Novel Molecule Targeting KRAS
G12C-Mutant Solid Tumors
Abstract #446PD, Poster
Discussion, Saturday, Sept. 28,
session at 4:30 p.m. CEST, discussion
at 4:52 p.m. CEST in Alicante
Auditorium (Hall 3)
- A Phase 1 Study of AMG 160, a Half-Life Extended Bispecific
T-Cell Engager (HLE BiTE®) Immuno-Oncology Therapy
Targeting PSMA, in Patients (pts) With Metastatic
Castration-Resistant Prostate Cancer (mCRPC)
Abstract
#895TiP, Poster Presentation, Monday, Sept.
30, at noon CEST in Poster
Area (Hall 4), Fira Gran Via
IMLYGIC
- Primary 2-Year Results of the Phase 2, Multicenter,
Randomized, Open-Label Trial of Efficacy and Safety for Talimogene
Laherparepvec (T-VEC) Neoadjuvant (neo) Treatment (tx) Plus Surgery
vs. Immediate Surgery in Patients (pts) With Resectable Stage
IIIB-IVM1a Melanoma
Abstract #LBA66, Oral Presentation,
Saturday, Sept. 28, session and
lecture at 8:30 a.m. CEST in Cordoba
Auditorium (Hall 7)
- Talimogene Laherparepvec (T-VEC) in Combination (combo) With
Ipilimumab (ipi) Versus ipi Alone for Advanced Melanoma: 3-Year
Landmark Analysis of a Randomized, Open-Label Phase 2
Trial
Abstract #LBA70, Poster Discussion, Saturday, Sept. 28, session and discussion at
2:45 p.m. CEST in Granada Auditorium
(Hall 3)
- Efficacy of Talimogene Laherparepvec (T-VEC) in Melanoma
Patients (pts) With Locoregional Recurrence, Including In-transit
Metastases (ITM): Subgroup Analysis of the Phase III OPTiM
Study
Abstract #1342P, Poster Presentation, Monday, Sept. 30, at noon
CEST in Poster Area (Hall 4), Fira
Gran Via
XGEVA® (denosumab)
- Use of Skeletal-Related Events Preventative Agents in
Patients With Solid Tumors and Bone Metastases in Central Denmark
Abstract #1793P, Poster
Presentation, Saturday, Sept. 28, at
noon CEST in Poster Area (Hall 4),
Fira Gran Via
- Adherence to ESMO 2014 Guidelines on Bone-Targeting Agent
Initiation for Breast and Prostate Cancer Patients: Real-World
Insights From Practicing European Physicians
Abstract
#1792P, Poster Presentation, Saturday, Sept.
28, at noon CEST in Poster
Area (Hall 4), Fira Gran Via
- Patterns of Care for Patients With Metastatic Bone Disease
in Solid Tumors – a Cross-Sectional Study (SAKK
95/16)
Abstract #1797P, Poster Presentation, Saturday, Sept. 28, at noon CEST in Poster Area (Hall 4), Fira Gran Via
- Utilization Pattern of Bone Targeting Agents in Patients
With Solid Tumor in Taiwan,
Hong Kong and
Korea
Abstract #379P, Poster Presentation, Sunday, Sept. 29, at noon
CEST in Poster Area (Hall 4), Fira
Gran Via
Vectibix® (panitumumab)
- Sequential RAS Mutation Testing in cfDNA in RAS Wild Type
(wt) Metastatic Colorectal Cancer (mCRC) Patients (p) Treated With
Panitumumab (P) and Chemotherapy (CT) in First Line (1L) PERSEIDA
Study
Abstract #531PD, Poster Discussion, Sunday, Sept. 29, session at 3 p.m. CEST, discussion at 3:25 p.m. CEST in Cordoba Atrium (Hall 7),
Fira Gran Via
- Early Tumour Shrinkage (ETS), Depth of Response (DpR) and
Associated Survival Outcomes in Patients (pts) With RAS Wild Type
(WT) Metastatic Colorectal Cancer (mCRC) Classified According to
Köhne Prognostic Category: Retrospective Analysis of the
Panitumumab (Pmab) PRIME Study
Abstract #572P, Poster
Presentation, Sunday, Sept. 29, at
noon CEST in Poster Area (Hall 4),
Fira Gran Via
- Middle East & North
Africa Registry to Characterize RAS Mutation Status and Tumor
Specifications in Recently Diagnosed Patients With Metastatic
Colorectal Cancer (MORE-RAS Study)
Abstract #656P, Poster
Presentation, Sunday, Sept. 29, at
noon CEST in Poster Area (Hall 4),
Fira Gran Via
- Quality of Life During 1st-Line FOLFOXIRI+/- Panitumumab in
RAS Wild-type Metastatic Colorectal Cancer: Results From the
Randomized VOLFI Trial (AIO KRK-0109)
Abstract #580P, Poster
Presentation, Sunday, Sept. 29, at
noon CEST in Poster Area (Hall 4),
Fira Gran Via
- Final Results of a Phase II Study of Induction Chemotherapy
(CT) With Paclitaxel (PTX) and Panitumumab (P) Followed by
Radiotherapy (RT) and P in Patients (pts) With Locally Advanced
Head and Neck Cancer (LAHNC) No Candidates to Platinum: Study
PANTERA
Abstract #1128P, Poster Presentation, Monday, Sept. 30, at noon
CEST in Poster Area (Hall 4), Fira
Gran Via
About KRAS
The subject of more than three
decades of research, the RAS gene family are the most
frequently mutated oncogenes in human cancers.1,2 Within
this family, KRAS is the most prevalent variant and is
particularly common in solid tumors.2 A specific
mutation known as KRAS G12C accounts for approximately 13%
of non-small cell lung cancers, three to five percent of colorectal
cancers and one to two percent of numerous other solid
tumors.3 Approximately 30,000 patients are diagnosed
each year in the United States
(U.S.) with KRAS G12C-driven cancers.4
KRASG12C 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 tumor types.
About BiTE® Technology
Bispecific T cell
engager (BiTE®) technology is a targeted immuno-oncology
platform that is designed to engage patients' 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 leads 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 more than a dozen BiTE molecules
across a broad range of hematologic malignancies and solid tumors,
further investigating BiTE technology with the goal of enhancing
patient experience and therapeutic potential.
About IMLYGIC® (talimogene
laherparepvec)
IMLYGIC is a genetically modified herpes
simplex type 1 virus that is injected directly into tumors. IMLYGIC
replicates inside tumor cells and produces GM-CSF, an
immunostimulatory protein. IMLYGIC then causes the cell to rupture
and die in a process called lysis. The rupture of the cancer cells
causes the release of tumor-derived antigens, which together with
virally derived GM-CSF may help to promote an anti-tumor immune
response. However, the exact mechanism of action is unknown.
IMLYGIC is the first oncolytic viral therapy approved by
the U.S. Food and Drug Administration (FDA) and
European Medicines Agency (EMA) based on therapeutic benefit
demonstrated in a pivotal study. IMLYGIC is a genetically modified
oncolytic viral therapy indicated for the local treatment of
unresectable cutaneous, subcutaneous, and nodal lesions in patients
with melanoma recurrent after initial surgery. IMLYGIC has not been
shown to improve overall survival (OS) or have an effect on
visceral metastases.
INDICATION & LIMITATIONS OF
USE
IMLYGIC® (talimogene laherparepvec) is a
genetically modified oncolytic viral therapy indicated for the
local treatment of unresectable cutaneous, subcutaneous, and nodal
lesions in patients with melanoma recurrent after initial
surgery.
Limitations of use: IMLYGIC® has not been
shown to improve overall survival or have an effect on visceral
metastases.
IMPORTANT SAFETY INFORMATION
Contraindications
- Do not administer IMLYGIC® to immunocompromised
patients, including those with a history of primary or acquired
immunodeficient states, leukemia, lymphoma, AIDS or other clinical
manifestations of infection with human immunodeficiency viruses,
and those on immunosuppressive therapy, due to the risk of
life-threatening disseminated herpetic infection.
- Do not administer IMLYGIC® to pregnant
patients.
Warnings and Precautions
- Accidental exposure to IMLYGIC® may lead to
transmission of IMLYGIC® and herpetic infection,
including during preparation and administration. Health care
providers, close contacts, pregnant women, and newborns should
avoid direct contact with injected lesions, dressings, or body
fluids of treated patients. The affected area in exposed
individuals should be cleaned thoroughly with soap and water and/or
a disinfectant.
- Caregivers should wear protective gloves when assisting
patients in applying or changing occlusive dressings and observe
safety precautions for disposal of used dressings, gloves, and
cleaning materials. Exposed individuals should clean the affected
area thoroughly with soap and water and/or a disinfectant.
- To prevent possible inadvertent transfer of
IMLYGIC® to other areas of the body, patients
should be advised to avoid touching or scratching injection sites
or occlusive dressings.
- Herpetic infections: Herpetic infections (including cold sores
and herpetic keratitis) have been reported in
IMLYGIC®-treated patients. Disseminated herpetic
infection may also occur in immunocompromised patients. Patients
who develop suspicious herpes-like lesions should follow standard
hygienic practices to prevent viral transmission.
- Patients or close contacts with suspected signs or symptoms of
a herpetic infection should contact their health care provider to
evaluate the lesions. Suspected herpetic lesions should be reported
to Amgen at 1-855-IMLYGIC (1-855-465-9442). Patients or close
contacts have the option of follow-up testing for further
characterization of the infection.
- IMLYGIC® is sensitive to acyclovir. Acyclovir
or other antiviral agents may interfere with the effectiveness of
IMLYGIC®. Consider the risks and benefits of
IMLYGIC® treatment before administering antiviral
agents to manage herpetic infection.
- Injection Site Complications: Necrosis or ulceration of tumor
tissue may occur during IMLYGIC® treatment.
Cellulitis and systemic bacterial infection have been reported in
clinical studies. Careful wound care and infection precautions are
recommended, particularly if tissue necrosis results in open
wounds.
- Impaired healing at the injection site has been reported.
IMLYGIC® may increase the risk of impaired healing
in patients with underlying risk factors (eg, previous radiation at
the injection site or lesions in poorly vascularized areas). If
there is persistent infection or delayed healing of the injection
site, consider the risks and benefits of continuing treatment.
- Immune-Mediated events including glomerulonephritis,
vasculitis, pneumonitis, worsening psoriasis, and vitiligo have
been reported in patients treated with IMLYGIC®.
Consider the risks and benefits of IMLYGIC® before
initiating treatment in patients who have underlying autoimmune
disease or before continuing treatment in patients who develop
immune-mediated events.
- Plasmacytoma at the Injection Site: Plasmacytoma in proximity
to the injection site has been reported in a patient with
smoldering multiple myeloma after
IMLYGIC® administration in a clinical study.
Consider the risks and benefits of IMLYGIC® in
patients with multiple myeloma or in whom plasmacytoma develops
during treatment.
- Obstructive Airway Disorder: Obstructive airway disorder has
been reported following IMLYGIC® treatment. Use
caution when injecting lesions close to major airways.
Adverse Reactions
- The most commonly reported adverse drug reactions (≥ 25%) in
IMLYGIC®-treated patients were fatigue, chills, pyrexia,
nausea, influenza-like illness, and injection site pain. Pyrexia,
chills, and influenza-like illness can occur at any time during
IMLYGIC® treatment, but were more frequent during
the first 3 months of treatment.
- The most common Grade 3 or higher adverse reaction was
cellulitis.
Please see www.Imlygic.com for full Prescribing Information,
including Medication Guide.
About XGEVA® (denosumab)
XGEVA targets
the RANKL pathway to prevent the formation, function and survival
of osteoclasts, which break down bone. XGEVA is indicated for the
prevention of skeletal-related events in patients with multiple
myeloma and in patients with bone metastases from solid tumors.
XGEVA is also indicated for treatment of adults and skeletally
mature adolescents with giant cell tumor of bone that is
unresectable or where surgical resection is likely to result in
severe morbidity and for the treatment of hypercalcemia of
malignancy refractory to bisphosphonate therapy.
INDICATIONS
XGEVA® is indicated for
the prevention of skeletal-related events in patients with multiple
myeloma and in patients with bone metastases from solid
tumors. XGEVA® is indicated for treatment of
adults and skeletally mature adolescents with giant cell tumor of
bone that is unresectable or where surgical resection is likely to
result in severe morbidity. XGEVA® is indicated for
the treatment of hypercalcemia of malignancy refractory to
bisphosphonate therapy.
IMPORTANT SAFETY INFORMATION
Important Safety Information
Hypocalcemia
Pre-existing hypocalcemia must be
corrected prior to initiating therapy with XGEVA®.
XGEVA® can cause severe symptomatic hypocalcemia,
and fatal cases have been reported. Monitor calcium levels,
especially in the first weeks of initiating therapy, and administer
calcium, magnesium, and vitamin D as necessary. Monitor levels more
frequently when XGEVA® is administered with other
drugs that can also lower calcium levels. Advise patients to
contact a healthcare professional for symptoms of hypocalcemia.
An increased risk of hypocalcemia has been observed in clinical
trials of patients with increasing renal dysfunction, most commonly
with severe dysfunction (creatinine clearance less than 30
mL/minute and/or on dialysis), and with inadequate/no calcium
supplementation. Monitor calcium levels and calcium and vitamin D
intake.
Hypersensitivity
XGEVA® is
contraindicated in patients with known clinically significant
hypersensitivity to XGEVA®, including anaphylaxis that
has been reported with use of XGEVA®. Reactions may
include hypotension, dyspnea, upper airway edema, lip swelling,
rash, pruritus, and urticaria. If an anaphylactic or other
clinically significant allergic reaction occurs, initiate
appropriate therapy and discontinue XGEVA® therapy
permanently.
Drug Products with Same Active Ingredient
Patients
receiving XGEVA® should not take
Prolia® (denosumab).
Osteonecrosis of the Jaw
Osteonecrosis of the jaw
(ONJ) has been reported in patients receiving XGEVA®,
manifesting as jaw pain, osteomyelitis, osteitis, bone erosion,
tooth or periodontal infection, toothache, gingival ulceration, or
gingival erosion. Persistent pain or slow healing of the mouth or
jaw after dental surgery may also be manifestations of ONJ. In
clinical trials in patients with cancer, the incidence of ONJ was
higher with longer duration of exposure.
Patients with a history of tooth extraction, poor oral hygiene,
or use of a dental appliance are at a greater risk to develop ONJ.
Other risk factors for the development of ONJ include
immunosuppressive therapy, treatment with angiogenesis inhibitors,
systemic corticosteroids, diabetes, and gingival infections.
Perform an oral examination and appropriate preventive dentistry
prior to the initiation of XGEVA® and periodically
during XGEVA® therapy. Advise patients regarding
oral hygiene practices. Avoid invasive dental procedures during
treatment with XGEVA®. Consider temporarily interrupting
XGEVA® therapy if an invasive dental procedure must
be performed.
Patients who are suspected of having or who develop ONJ while on
XGEVA® should receive care by a dentist or an oral
surgeon. In these patients, extensive dental surgery to treat ONJ
may exacerbate the condition.
Atypical Subtrochanteric and Diaphyseal Femoral
Fracture
Atypical femoral fracture has been reported with
XGEVA®. These fractures can occur anywhere in the
femoral shaft from just below the lesser trochanter to above the
supracondylar flare and are transverse or short oblique in
orientation without evidence of comminution.
Atypical femoral fractures most commonly occur with minimal or
no trauma to the affected area. They may be bilateral and many
patients report prodromal pain in the affected area, usually
presenting as dull, aching thigh pain, weeks to months before a
complete fracture occurs. A number of reports note that patients
were also receiving treatment with glucocorticoids (e.g.
prednisone) at the time of fracture. During
XGEVA® treatment, patients should be advised to
report new or unusual thigh, hip, or groin pain. Any patient who
presents with thigh or groin pain should be suspected of having an
atypical fracture and should be evaluated to rule out an incomplete
femur fracture. Patients presenting with an atypical femur fracture
should also be assessed for symptoms and signs of fracture in the
contralateral limb. Interruption of XGEVA® therapy
should be considered, pending a risk/benefit assessment, on an
individual basis.
Hypercalcemia Following Treatment Discontinuation in Patients
with Giant Cell Tumor of Bone (GCTB) and in Patients with Growing
Skeletons
Clinically significant hypercalcemia requiring
hospitalization and complicated by acute renal injury has been
reported in XGEVA®-treated patients with GCTB and in
patients with growing skeletons within one year of treatment
discontinuation. Monitor patients for signs and symptoms of
hypercalcemia after treatment discontinuation and treat
appropriately.
Multiple Vertebral Fractures (MVF) Following Treatment
Discontinuation
Multiple vertebral fractures (MVF) have been
reported following discontinuation of treatment with denosumab.
Patients at higher risk for MVF include those with risk factors for
or a history of osteoporosis or prior fractures. When
XGEVA® treatment is discontinued, evaluate the
individual patient's risk for vertebral fractures.
Embryo-Fetal Toxicity
XGEVA® can cause
fetal harm when administered to a pregnant woman. Based on findings
in animals, XGEVA® is expected to result in adverse
reproductive effects.
Advise females of reproductive potential to use effective
contraception during therapy, and for at least 5 months after the
last dose of XGEVA®. Apprise the patient of the
potential hazard to a fetus if XGEVA® is used
during pregnancy or if the patient becomes pregnant while patients
are exposed to XGEVA®.
Adverse Reactions
The most common adverse reactions in
patients receiving XGEVA® with bone metastasis from
solid tumors were fatigue/asthenia, hypophosphatemia, and nausea.
The most common serious adverse reaction was dyspnea. The most
common adverse reactions resulting in discontinuation were
osteonecrosis and hypocalcemia.
For multiple myeloma patients receiving XGEVA®, the
most common adverse reactions were diarrhea, nausea, anemia, back
pain, thrombocytopenia, peripheral edema, hypocalcemia, upper
respiratory tract infection, rash, and headache. The most common
serious adverse reaction was pneumonia. The most common adverse
reaction resulting in discontinuation of XGEVA® was
osteonecrosis of the jaw.
The most common adverse reactions in patients receiving
XGEVA® for giant cell tumor of bone were
arthralgia, headache, nausea, back pain, fatigue, and pain in
extremity. The most common serious adverse reactions were
osteonecrosis of the jaw and osteomyelitis.
The most common adverse reactions resulting in discontinuation
of XGEVA® were osteonecrosis of the jaw and tooth
abscess or tooth infection.
The most common adverse reactions in patients receiving
XGEVA® for hypercalcemia of malignancy were nausea,
dyspnea, decreased appetite, headache, peripheral edema, vomiting,
anemia, constipation, and diarrhea.
Please visit www.xgeva.com for Full U.S. 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 (eg, 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
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.
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
This news release contains forward-looking statements that are
based on the current expectations and beliefs of Amgen. All
statements, other than statements of historical fact, are
statements that could be deemed forward-looking statements,
including estimates of revenues, operating margins, capital
expenditures, cash, other financial metrics, expected legal,
arbitration, political, regulatory or clinical results or
practices, customer and prescriber patterns or practices,
reimbursement activities and outcomes and other such estimates and
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 identification of new product candidates or
development of new indications for existing products cannot be
guaranteed and movement from concept to product is uncertain;
consequently, there can be no guarantee that any particular product
candidate or development of a new indication for an existing
product will be successful and become a commercial product.
Further, preclinical results do not guarantee safe and effective
performance of product candidates in humans. The complexity of the
human body cannot be perfectly, or sometimes, even adequately
modeled by computer or cell culture systems or animal models. The
length of time that it takes for us to complete clinical trials and
obtain regulatory approval for product marketing has in the past
varied and we expect similar variability in the future. Even when
clinical trials are successful, regulatory authorities may question
the sufficiency for approval of the trial endpoints we have
selected. We develop product candidates internally and through
licensing collaborations, partnerships and joint ventures. Product
candidates that are derived from relationships may be subject to
disputes between the parties or may prove to be not as effective or
as safe as we may have believed at the time of entering into such
relationship. Also, we or others could identify safety, side
effects or manufacturing problems with our products, including our
devices, after they are on the market.
Our results may be affected by our ability to successfully
market both new and existing products domestically and
internationally, clinical and regulatory developments involving
current and future products, sales growth of recently launched
products, competition from other products including biosimilars,
difficulties or delays in manufacturing our products and global
economic conditions. In addition, sales of our products are
affected by pricing pressure, political and public scrutiny and
reimbursement policies imposed by third-party payers, including
governments, private insurance plans and managed care providers and
may be affected by regulatory, clinical and guideline developments
and domestic and international trends toward managed care and
healthcare cost containment. Furthermore, our research, testing,
pricing, marketing and other operations are subject to extensive
regulation by domestic and foreign government regulatory
authorities. Our business may be impacted by government
investigations, litigation and product liability claims. In
addition, our business may be impacted by the adoption of new tax
legislation or exposure to additional tax liabilities. If we fail
to meet the compliance obligations in the corporate integrity
agreement between us and the U.S. government, we could become
subject to significant sanctions. Further, while we routinely
obtain patents for our products and technology, the protection
offered by our patents and patent applications may be challenged,
invalidated or circumvented by our competitors, or we may fail to
prevail in present and future intellectual property litigation. We
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. We rely on collaborations with third parties
for the 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
our products that implicate an entire class of products could have
a material adverse effect on sales of the affected products and on
our business and results of operations. Our efforts to acquire
other companies or products and to integrate the operations of
companies we have acquired may not be successful. A breakdown,
cyberattack or information security breach could compromise the
confidentiality, integrity and availability of our systems and our
data. Our stock price is volatile and may be affected by a number
of events. Our business performance could affect or limit the
ability of our Board 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 all.
The 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 & Drug Administration or the European Medicines Agency 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
Trish Hawkins, 805-447-5631
(Media)
Jessica Akopyan, 805-447-0974
(Media)
Arvind Sood, 805-447-1060
(Investors)
References:
- Cox A, et al. Drugging the undruggable RAS: Mission
possible? Nat Rev Drug Discov. 2014
Nov;13(11):828-51.
- Fernandez-Medarde A, Santos E. Ras in cancer and
developmental diseases. Genes Cancer. 2011
Mar;2(3):344-58.
- Lipford, JR. Pre-clinical development of AMG 510: the first
inhibitor of KRASG12C in clinical testing. Oral presentation at
AACR 2019, Atlanta, GA. March 29-April
3, 2019.
- Stephen AG, et al. Dragging ras back in the ring. Cancer
Cell. 2014 Mar 17;25(3):272-81.
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SOURCE Amgen