ROCKLAND, Mass. and
NEW YORK, March 13, 2020 /PRNewswire/ -- EMD Serono,
the biopharmaceutical business of Merck KGaA, Darmstadt,
Germany in the US and Canada, and Pfizer Inc. (NYSE: PFE) today
announced an update from the Phase III JAVELIN Head and Neck 100
study evaluating avelumab in addition to chemoradiotherapy (CRT)
versus standard-of-care CRT in patients with untreated locally
advanced squamous cell carcinoma of the head and neck (LA
SCCHN). The alliance has accepted the recommendation of the
independent Data Monitoring Committee (DMC) to terminate the
JAVELIN Head and Neck 100 trial, as the study is unlikely to show a
statistically significant improvement in the primary endpoint of
progression-free survival (PFS) based on a preplanned interim
analysis. A detailed analysis of the Phase III JAVELIN Head and
Neck 100 study is being conducted and study findings will be shared
with the scientific community.
There has been limited innovation for patients with locally
advanced SCCHN over the past 10 years.1 Despite
aggressive standard-of-care treatment with high-dose chemotherapy
combined with radiotherapy, LA SCCHN will ultimately recur in a
large proportion of patients.2 In recognition of the
unmet need for additional treatment options that can prevent
recurrence or metastatic disease,3 the alliance
initiated the JAVELIN Head and Neck 100 trial, which is the first
Phase III study to report topline results for an immune checkpoint
inhibitor in combination with CRT in LA SCCHN.
About JAVELIN Head and Neck 100
JAVELIN Head and
Neck 100 (NCT02952586) is a Phase III, randomized, double-blind,
placebo-controlled, parallel-arm study investigating treatment with
avelumab plus standard-of-care CRT followed by avelumab maintenance
versus CRT alone in patients with previously untreated LA SCCHN. A
total of 697 patients who had not received prior therapy for
locally advanced SCCHN and were eligible for CRT with curative
intent were randomly assigned to receive avelumab plus CRT or CRT
alone. The primary endpoint was PFS per modified Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary
endpoints included overall survival (OS), time to locoregional
failure, time to distant metastatic failure, overall response,
duration of response and pathologic complete response.
About Head and Neck Cancer
Head and neck cancer is the
sixth most common cancer worldwide.4 In 2016, there were
nearly 150,000 newly diagnosed cases in the United States, Japan and Europe.4 Approximately 60% of
people are diagnosed with head and neck cancer when their disease
has already progressed to the locally advanced stage (Stage
III-IVB).5 At this stage, the cancer has spread from its
site of origin to local lymph nodes, but not another part of the
body.6 Standard of care for these patients includes
high-dose chemotherapy combined with radiotherapy.7
About BAVENCIO®
(avelumab)
BAVENCIO is a human anti-programmed death
ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical
models to engage both the adaptive and innate immune functions. By
blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has
been shown to release the suppression of the T cell-mediated
antitumor immune response in preclinical models.8-10 In
November 2014, Merck KGaA, Darmstadt,
Germany, and Pfizer announced a
strategic alliance to co-develop and co-commercialize
BAVENCIO.
BAVENCIO Approved Indications
BAVENCIO®
(avelumab) in combination with axitinib is indicated in the US for
the first-line treatment of patients with advanced renal cell
carcinoma (RCC).
In the US, the FDA granted accelerated approval for BAVENCIO for
the treatment of (i) adults and pediatric patients 12 years and
older with metastatic Merkel cell carcinoma (mMCC) and (ii)
patients with locally advanced or metastatic urothelial carcinoma
(mUC) who have disease progression during or following
platinum-containing chemotherapy, or have disease progression
within 12 months of neoadjuvant or adjuvant treatment with
platinum-containing chemotherapy. These indications are approved
under accelerated approval based on tumor response rate and
duration of response. Continued approval for these indications may
be contingent upon verification and description of clinical benefit
in confirmatory trials.
Avelumab is currently approved for patients with MCC in 50
countries globally, with the majority of these approvals in a broad
indication that is not limited to a specific line of treatment.
BAVENCIO Important Safety Information from the US
FDA-Approved Label
BAVENCIO can cause immune-mediated
pneumonitis, including fatal cases. Monitor patients for signs
and symptoms of pneumonitis, and evaluate suspected cases with
radiographic imaging. Administer corticosteroids for Grade 2 or
greater pneumonitis. Withhold BAVENCIO for moderate (Grade 2) and
permanently discontinue for severe (Grade 3), life-threatening
(Grade 4), or recurrent moderate (Grade 2) pneumonitis. Pneumonitis
occurred in 1.2% of patients, including one (0.1%) patient with
Grade 5, one (0.1%) with Grade 4, and five (0.3%) with Grade 3.
BAVENCIO can cause hepatotoxicity and immune-mediated
hepatitis, including fatal cases. Monitor patients for abnormal
liver tests prior to and periodically during treatment. Administer
corticosteroids for Grade 2 or greater hepatitis. Withhold BAVENCIO
for moderate (Grade 2) immune-mediated hepatitis until resolution
and permanently discontinue for severe (Grade 3) or
life-threatening (Grade 4) immune-mediated hepatitis.
Immune-mediated hepatitis occurred with BAVENCIO as a single agent
in 0.9% of patients, including two (0.1%) patients with Grade 5,
and 11 (0.6%) with Grade 3.
BAVENCIO in combination with
axitinib can cause hepatotoxicity with higher than
expected frequencies of Grade 3 and 4 alanine aminotransferase
(ALT) and aspartate aminotransferase (AST) elevation. Consider more
frequent monitoring of liver enzymes as compared to when the drugs
are used as monotherapy. Withhold BAVENCIO and axitinib for
moderate (Grade 2) hepatotoxicity and permanently discontinue the
combination for severe or life-threatening (Grade 3 or 4)
hepatotoxicity. Administer corticosteroids as needed. In patients
treated with BAVENCIO in combination with axitinib, Grades 3
and 4 increased ALT and AST occurred in 9% and 7% of patients,
respectively, and immune-mediated hepatitis occurred in 7% of
patients, including 4.9% with Grade 3 or 4.
BAVENCIO can cause immune-mediated colitis. Monitor
patients for signs and symptoms of colitis. Administer
corticosteroids for Grade 2 or greater colitis. Withhold BAVENCIO
until resolution for moderate or severe (Grade 2 or 3) colitis
until resolution. Permanently discontinue for life-threatening
(Grade 4) or recurrent (Grade 3) colitis upon reinitiation of
BAVENCIO. Immune-mediated colitis occurred in 1.5% of patients,
including seven (0.4%) with Grade 3.
BAVENCIO can cause immune-mediated endocrinopathies,
including adrenal insufficiency, thyroid disorders, and type 1
diabetes mellitus.
Monitor patients for signs and
symptoms of adrenal insufficiency during and after
treatment, and administer corticosteroids as appropriate. Withhold
BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) adrenal
insufficiency. Adrenal insufficiency was reported in 0.5% of
patients, including one (0.1%) with Grade 3.
Thyroid disorders can occur
at any time during treatment. Monitor patients for changes in
thyroid function at the start of treatment, periodically during
treatment, and as indicated based on clinical evaluation. Manage
hypothyroidism with hormone replacement therapy and hyperthyroidism
with medical management. Withhold BAVENCIO for severe (Grade 3) or
life-threatening (Grade 4) thyroid disorders. Thyroid disorders,
including hypothyroidism, hyperthyroidism, and thyroiditis, were
reported in 6% of patients, including three (0.2%) with Grade
3.
Type 1 diabetes mellitus
including diabetic ketoacidosis: Monitor patients for hyperglycemia
or other signs and symptoms of diabetes. Withhold BAVENCIO and
administer antihyperglycemics or insulin in patients with severe or
life-threatening (Grade ≥3) hyperglycemia, and resume treatment
when metabolic control is achieved. Type 1 diabetes mellitus
without an alternative etiology occurred in 0.1% of patients,
including two cases of Grade 3 hyperglycemia.
BAVENCIO can cause immune-mediated nephritis and renal
dysfunction. Monitor patients for elevated serum creatinine
prior to and periodically during treatment. Administer
corticosteroids for Grade 2 or greater nephritis. Withhold BAVENCIO
for moderate (Grade 2) or severe (Grade 3) nephritis until
resolution to Grade 1 or lower. Permanently discontinue BAVENCIO
for life-threatening (Grade 4) nephritis. Immune-mediated nephritis
occurred in 0.1% of patients.
BAVENCIO can result in other severe and fatal immune-mediated
adverse reactions involving any organ system during treatment
or after treatment discontinuation. For suspected immune-mediated
adverse reactions, evaluate to confirm or rule out an
immune-mediated adverse reaction and to exclude other causes.
Depending on the severity of the adverse reaction, withhold or
permanently discontinue BAVENCIO, administer high-dose
corticosteroids, and initiate hormone replacement therapy, if
appropriate. Resume BAVENCIO when the immune-mediated adverse
reaction remains at Grade 1 or lower following a corticosteroid
taper. Permanently discontinue BAVENCIO for any severe (Grade 3)
immune-mediated adverse reaction that recurs and for any
life-threatening (Grade 4) immune-mediated adverse reaction. The
following clinically significant immune-mediated adverse reactions
occurred in less than 1% of 1738 patients treated with BAVENCIO as
a single agent or in 489 patients who received BAVENCIO in
combination with axitinib: myocarditis including fatal cases,
pancreatitis including fatal cases, myositis, psoriasis, arthritis,
exfoliative dermatitis, erythema multiforme, pemphigoid,
hypopituitarism, uveitis, Guillain-Barré syndrome, and systemic
inflammatory response.
BAVENCIO can cause severe or life-threatening
infusion-related reactions. Premedicate patients with an
antihistamine and acetaminophen prior to the first 4 infusions and
for subsequent infusions based upon clinical judgment and
presence/severity of prior infusion reactions. Monitor patients for
signs and symptoms of infusion-related reactions, including
pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back
pain, abdominal pain, and urticaria. Interrupt or slow the rate of
infusion for mild (Grade 1) or moderate (Grade 2) infusion-related
reactions. Permanently discontinue BAVENCIO for severe (Grade 3) or
life-threatening (Grade 4) infusion-related reactions.
Infusion-related reactions occurred in 25% of patients, including
three (0.2%) patients with Grade 4 and nine (0.5%) with Grade
3.
BAVENCIO in combination with axitinib can cause major
adverse cardiovascular events (MACE) including severe and fatal
events. Consider baseline and periodic evaluations of left
ventricular ejection fraction. Monitor for signs and symptoms of
cardiovascular events. Optimize management of cardiovascular risk
factors, such as hypertension, diabetes, or dyslipidemia.
Discontinue BAVENCIO and axitinib for Grade 3-4 cardiovascular
events. MACE occurred in 7% of patients with advanced RCC
treated with BAVENCIO in combination with axitinib compared to 3.4%
treated with sunitinib. These events included death due to cardiac
events (1.4%), Grade 3-4 myocardial infarction (2.8%), and Grade
3-4 congestive heart failure (1.8%).
BAVENCIO can cause fetal harm when administered to a
pregnant woman. Advise patients of the potential risk to a fetus
including the risk of fetal death. Advise females of childbearing
potential to use effective contraception during treatment with
BAVENCIO and for at least 1 month after the last dose of BAVENCIO.
It is not known whether BAVENCIO is excreted in human milk. Advise
a lactating woman not to breastfeed during treatment and for
at least 1 month after the last dose of BAVENCIO due to the
potential for serious adverse reactions in breastfed infants.
The most common adverse reactions (all grades, ≥ 20%) in
patients with metastatic Merkel cell carcinoma (MCC) were fatigue
(50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%),
infusion-related reaction (22%), rash (22%), decreased appetite
(20%), and peripheral edema (20%).
Selected treatment-emergent laboratory abnormalities (all
grades, ≥ 20%) in patients with metastatic MCC were lymphopenia
(49%), anemia (35%), increased aspartate aminotransferase (34%),
thrombocytopenia (27%), and increased alanine aminotransferase
(20%).
The most common adverse reactions (all grades, ≥ 20%) in
patients with locally advanced or metastatic urothelial carcinoma
(UC) were fatigue (41%), infusion-related reaction (30%),
musculoskeletal pain (25%), nausea (24%), decreased
appetite/hypophagia (21%), and urinary tract infection (21%).
Selected laboratory abnormalities (Grades 3-4, ≥ 3%) in patients
with locally advanced or metastatic UC were hyponatremia (16%),
increased gamma-glutamyltransferase (12%), lymphopenia (11%),
hyperglycemia (9%), increased alkaline phosphatase (7%), anemia
(6%), increased lipase (6%), hyperkalemia (3%), and increased
aspartate aminotransferase (3%).
Fatal adverse reactions occurred in 1.8% of patients with
advanced renal cell carcinoma (RCC) receiving BAVENCIO in
combination with axitinib. These included sudden cardiac death
(1.2%), stroke (0.2%), myocarditis (0.2%), and necrotizing
pancreatitis (0.2%).
The most common adverse reactions (all grades, ≥20%) in patients
with advanced RCC receiving BAVENCIO in combination with axitinib
(vs sunitinib) were diarrhea (62% vs 48%), fatigue (53% vs 54%),
hypertension (50% vs 36%), musculoskeletal pain (40% vs 33%),
nausea (34% vs 39%), mucositis (34% vs 35%), palmar-plantar
erythrodysesthesia (33% vs 34%), dysphonia (31% vs 3.2%), decreased
appetite (26% vs 29%), hypothyroidism (25% vs 14%), rash (25% vs
16%), hepatotoxicity (24% vs 18%), cough (23% vs 19%), dyspnea (23%
vs 16%), abdominal pain (22% vs 19%), and headache (21% vs
16%).
Selected laboratory abnormalities (all grades, ≥20%) worsening
from baseline in patients with advanced RCC receiving BAVENCIO in
combination with axitinib (vs sunitinib) were blood triglycerides
increased (71% vs 48%), blood creatinine increased (62% vs 68%),
blood cholesterol increased (57% vs 22%), alanine aminotransferase
increased (ALT) (50% vs 46%), aspartate aminotransferase increased
(AST) (47% vs 57%), blood sodium decreased (38% vs 37%), lipase
increased (37% vs 25%), blood potassium increased (35% vs 28%),
platelet count decreased (27% vs 80%), blood bilirubin increased
(21% vs 23%), and hemoglobin decreased (21% vs 65%).
Please see full US Prescribing Information and Medication Guide
available at http://www.BAVENCIO.com.
About Merck KGaA, Darmstadt, Germany-Pfizer
Alliance
Immuno-oncology is a top priority for Merck KGaA,
Darmstadt, Germany and Pfizer. The
global strategic alliance between Merck KGaA, Darmstadt,
Germany and Pfizer enables the
companies to benefit from each other's strengths and capabilities
and further explore the therapeutic potential of BAVENCIO, an
anti-PD-L1 antibody initially discovered and developed by Merck
KGaA, Darmstadt, Germany. The
immuno-oncology alliance is jointly developing and commercializing
BAVENCIO. The alliance is focused on developing high-priority
international clinical programs to investigate BAVENCIO as a
monotherapy as well as combination regimens, and is striving to
find new ways to treat cancer.
All Merck KGaA, Darmstadt, Germany, press releases are distributed by
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About EMD Serono, Inc.
EMD Serono - the
biopharmaceutical business of Merck KGaA, Darmstadt, Germany,
in the U.S. and Canada - is engaged in the discovery,
research and development of medicines for patients with difficult
to treat diseases. The business is committed to transforming lives
by developing and delivering meaningful solutions that help address
the therapeutic and support needs of individual patients. Building
on a proven legacy and deep expertise in neurology, fertility and
endocrinology, EMD Serono is developing potential new oncology and
immuno-oncology medicines while continuing to explore potential
therapeutic options for diseases such as psoriasis, lupus and MS.
Today, the business has approximately 1,500 employees around the
country with commercial, clinical and research operations based in
the company's home state
of Massachusetts. www.emdserono.com.
About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt,
Germany, a leading science and
technology company, operates across healthcare, life science and
performance materials. Around 57,000 employees work to make a positive
difference to millions of people's lives every day by creating more
joyful and sustainable ways to live. From advancing gene editing
technologies and discovering unique ways to treat the most
challenging diseases to enabling the intelligence of devices – the
company is everywhere. In 2019,
Merck KGaA, Darmstadt, Germany,
generated sales of € 16.2 billion
in 66 countries.
The company holds the global rights to the name and trademark
"Merck" internationally. The only exceptions are the United States and Canada, where the business sectors of Merck
KGaA, Darmstadt, Germany operate
as EMD Serono in healthcare, MilliporeSigma in life science, and
EMD Performance Materials. Since its founding 1668, scientific
exploration and responsible entrepreneurship have been key to the
company's technological and scientific advances. To this day, the
founding family remains the majority owner of the publicly listed
company.
Pfizer Inc.: Breakthroughs that change patients'
lives
At Pfizer, we apply science and our global resources
to bring therapies to people that extend and significantly improve
their lives. We strive to set the standard for quality, safety and
value in the discovery, development and manufacture of health care
products, including innovative medicines and vaccines. Every day,
Pfizer colleagues work across developed and emerging markets to
advance wellness, prevention, treatments and cures that challenge
the most feared diseases of our time. Consistent with our
responsibility as one of the world's premier innovative
biopharmaceutical companies, we collaborate with health care
providers, governments and local communities to support and expand
access to reliable, affordable health care around the world. For
more than 150 years, we have worked to make a difference for all
who rely on us. We routinely post information that may be important
to investors on our website at www.pfizer.com. In addition, to
learn more, please visit us on www.pfizer.com and follow us on
Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us
on Facebook at Facebook.com/Pfizer.
Pfizer Disclosure Notice
The information contained in
this release is as of March 13, 2020.
Pfizer assumes no obligation to update forward-looking
statements contained in this release as the result of new
information or future events or developments.
This release contains forward-looking information about BAVENCIO
(avelumab), the alliance between Merck KGaA, Darmstadt,
Germany, and Pfizer involving BAVENCIO and clinical
development plans, including their potential benefits, that
involves substantial risks and uncertainties that could cause
actual results to differ materially from those expressed or implied
by such statements. Risks and uncertainties include, among other
things, uncertainties regarding the commercial success of BAVENCIO;
the uncertainties inherent in research and development, including
the ability to meet anticipated clinical endpoints, commencement
and/or completion dates for our clinical trials, regulatory
submission dates, regulatory approval dates and/or launch dates, as
well as the possibility of unfavorable new clinical data and
further analyses of existing clinical data; risks associated with
interim data; the risk that clinical trial data are subject to
differing interpretations and assessments by regulatory
authorities; whether regulatory authorities will be satisfied with
the design of and results from our clinical studies; whether and
when any drug applications may be filed in any jurisdictions
for any potential indications for BAVENCIO or combination
therapies; whether and when regulatory authorities in any
jurisdictions where any applications are pending or may be
submitted for BAVENCIO or combination therapies may approve any
such applications, which will depend on myriad factors, including
making a determination as to whether the product's benefits
outweigh its known risks and determination of the product's
efficacy, and, if approved, whether they will be commercially
successful; decisions by regulatory authorities impacting labeling,
manufacturing processes, safety and/or other matters that could
affect the availability or commercial potential of BAVENCIO; and
competitive developments.
A further description of risks and uncertainties can be found in
Pfizer's Annual Report on Form 10-K for the fiscal year ended
December 31, 2019, and in its
subsequent reports on Form 10-Q, including in the sections thereof
captioned "Risk Factors" and "Forward-Looking Information and
Factors That May Affect Future Results", as well as in its
subsequent reports on Form 8-K, all of which are filed with the
U.S. Securities and Exchange Commission and available at
www.sec.gov and www.pfizer.com.
References
- Mandal R, et al. The head and neck cancer immune landscape and
its immunotherapeutic implications. JCI Insight.
2016;1(17):e89829.
- National Comprehensive Cancer Network. NCCN Clinical Practice
Guidelines: Head and Neck Cancers.
https://www.nccn.org/professionals/physician_gls/default.aspx.
Accessed March 2020.
- Porceddu SV, et al. Treating patients with locally advanced
squamous cell carcinoma of the head and neck unsuitable to receive
cisplatin-based therapy. Frontiers in Oncology.
2020;22.
- Tzong K. Head and neck cancer:
Epidemiology. Datamonitor. August
2017.
- Oksuz DC, et al. Recurrence patterns of locally advanced head
and neck squamous cell carcinoma after 3D conformal
(chemo)-radiotherapy. Radiation Oncology. 2011;6(54).
- Deschler DG, Moore MG, Smith RV, eds. Quick Reference Guide to
TNM Staging of Head and Neck Cancer and Neck Dissection
Classification, 4th ed. Alexandria,
VA: American Academy of Otolaryngology–Head and Neck Surgery
Foundation, 2014.
- Argiris A, et al. Evidence-Based Treatment Options in Recurrent
and/or Metastatic Squamous Cell Carcinoma of the Head and Neck.
Frontiers in Oncology. 2017;7:72.
- Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the
landscape of cancer immunotherapy. Cancer Control.
2014;21(3):231-237.
- Dahan R, Sega E, Engelhardt J, et al. FcγRs modulate the
anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis.
Cancer Cell. 2015;28(3):285-295.
- Boyerinas B, Jochems C, Fantini M, et al. Antibody-dependent
cellular cytotoxicity activity of a novel anti-PD-L1 antibody
avelumab (MSB0010718C) on human tumor cells. Cancer Immunol
Res. 2015;3(10):1148-1157.
Your
Contacts
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EMD Serono
Inc.
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Media
|
Noelle
Piscitelli
|
+1 781 427
4351
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Investor
Relations
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+49 6151
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Pfizer Inc., New
York, USA
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+1 212 733
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Relations
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|
+1 212 733
8160
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