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JAVELIN Renal 101 marks first Phase III study to evaluate
avelumab in combination with a small molecule tyrosine kinase
inhibitor therapy
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Combination approach leverages Pfizer’s broad oncology portfolio
and heritage in renal cell carcinoma
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First-line study evaluating avelumab in combination with INLYTA®
(axitinib) compared with SUTENT®
(sunitinib malate) monotherapy
Merck KGaA, Darmstadt, Germany, and Pfizer (NYSE: PFE) today announced
the treatment of the first patient in a Phase III study of avelumab*, an
investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in an
advanced renal cell carcinoma (RCC) setting. The study, JAVELIN Renal
101, is the first pivotal trial investigating avelumab in combination
with INLYTA® (axitinib), a tyrosine kinase inhibitor (TKI),
in patients with previously untreated advanced RCC, and the only Phase
III trial currently evaluating an anti-PD-L1 immunotherapy in
combination with a vascular endothelial growth factor (VEGF)-receptor
TKI in this setting. The current 5-year survival rate for patients with
distant metastatic RCC is approximately 12 percent.1
“Pfizer has a strong heritage in the treatment of metastatic RCC, and
through the strategic alliance with Merck KGaA, Darmstadt, Germany, we
aim to further accelerate the development of potential therapies to help
improve the lives of patients living with this disease,” said Chris
Boshoff, M.D., PhD., Vice President and Head of Early Development,
Translational and Immuno-Oncology at Pfizer Oncology. “As renal cell
carcinoma is an immunogenic type of tumor that can respond to
immunotherapy and to anti-angiogenic treatment, there is a strong
scientific rationale for combining avelumab with INLYTA® and
we believe that this combination may help improve outcomes for patients
with this cancer.”
JAVELIN Renal 101 is a multicenter, international, randomized (1:1),
open-label Phase III trial designed to evaluate the potential
superiority, assessed by the progression-free survival (PFS), of
first-line avelumab combined with INLYTA® compared with SUTENT®
(sunitinib malate) monotherapy, an oral, small-molecule, multi-targeted
receptor TKI, in patients with unresectable, locally advanced or
metastatic RCC with clear cell component. The study will enroll 583
patients across approximately 170 sites in Asia, Europe, Latin America
and North America.
“The first patient receiving treatment in this pivotal trial marks an
important milestone in the strategic immuno-oncology alliance between
Merck KGaA, Darmstadt, Germany, and Pfizer,” said Alise Reicin, M.D.,
Head of Global Clinical Development at the biopharma business of Merck
KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD
Serono. “As part of the JAVELIN clinical development program, we are
exploring the potential of innovative, rational combination therapies,
which combine avelumab with other treatment modalities to address
significant unmet needs that exist in challenging cancers, such as
advanced renal cell carcinoma.”
The clinical development program for avelumab now includes more than
1,600 patients who have been treated across more than 15 tumor types.
INLYTA® is currently approved in the United States for the
treatment of advanced RCC after failure of one prior systemic therapy.
INLYTA® is also approved by the European Medicines Agency for
use in the European Union in adult patients with advanced RCC after
failure of prior treatment with SUTENT® or a cytokine.
Following its approval in 2012, INLYTA® has become a standard
of care for second-line advanced RCC and has been used by an estimated
12,000 metastatic renal cell carcinoma patients in the United States.2
INLYTA® is under investigation in combination with
avelumab for the indication studied in this Phase III trial.
*Avelumab is the proposed International Non-proprietary Name for the
anti-PD-L1 monoclonal antibody (MSB0010718C). Avelumab is under clinical
investigation and has not been proven to be safe and effective. There is
no guarantee any product will be approved in the sought-after indication
by any health authority worldwide.
About Renal Cell Carcinoma
Renal cell carcinoma accounts globally for 2-3% of all malignancies.3
As of 2012, more than 338,000 new cases of kidney cancer were diagnosed
per year worldwide.4 In general, higher incidence rates of
renal cell carcinoma occur in Eastern Asia, North America and
Central/Eastern Europe.5 Early-stage renal cancers tend to
have a better prognosis, compared with advanced/metastatic renal cancers.6
The five-year survival rate for localized kidney and renal pelvis cancer
is approximately 90%.1 The five-year overall survival rate
for patients with distant metastatic RCC is approximately 12%.1
In the past 7 years, major advances have been made in the improvement of
clinical outcomes with the introduction of new therapies.7
The introduction of these therapies has extended median survival rates
for metastatic renal cell carcinoma.7
About Avelumab
Avelumab (also known as MSB0010718C) is an investigational fully human
anti-PD-L1 IgG1 monoclonal antibody. By inhibiting PD-L1 interactions,
avelumab is thought to enable the activation of T-cells and the adaptive
immune system. By retaining a native Fc-region, avelumab is thought to
potentially engage the innate immune system and induce
antibody-dependent cell-mediated cytotoxicity (ADCC). In November 2014,
Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic
alliance to co-develop and co-commercialize avelumab.
About INLYTA® (axitinib)
INLYTA is indicated for the treatment of advanced RCC after failure of
one prior systemic therapy. INLYTA, a kinase inhibitor, is an oral
therapy that is designed to inhibit tyrosine kinases, including vascular
endothelial growth factor (VEGF) receptors 1, 2 and 3; these receptors
can influence tumor growth, vascular angiogenesis and progression of
cancer (the spread of tumors).
Selected Safety Information for INLYTA®
(axitinib)
Hypertension including hypertensive crisis has been observed. Blood
pressure should be well-controlled prior to initiating INLYTA. Monitor
for hypertension and treat as needed. For persistent hypertension
despite use of anti-hypertensive medications, reduce the INLYTA dose.
Discontinue INLYTA if hypertension is severe and persistent despite use
of antihypertensive therapy and dose reduction of INLYTA, and
discontinuation should be considered if there is evidence of
hypertensive crisis.
Arterial and venous thrombotic events have been observed and can be
fatal. Use with caution in patients who are at increased risk for these
events.
Hemorrhagic events, including fatal events, have been reported. INLYTA
has not been studied in patients with evidence of untreated brain
metastasis or recent active gastrointestinal bleeding and should not be
used in those patients. If any bleeding requires medical intervention,
temporarily interrupt the INLYTA dose.
Cardiac failure has been observed and can be fatal. Monitor for signs or
symptoms of cardiac failure throughout treatment with INLYTA. Management
of cardiac failure may require permanent discontinuation of INLYTA.
Gastrointestinal perforation and fistula, including death, have
occurred. Use with caution in patients at risk for gastrointestinal
perforation or fistula. Monitor for symptoms of gastrointestinal
perforation or fistula periodically throughout treatment.
Hypothyroidism requiring thyroid hormone replacement has been reported.
Monitor thyroid function before initiation of, and periodically
throughout, treatment with INLYTA.
No formal studies of the effect of INLYTA on wound healing have been
conducted. Stop INLYTA at least 24 hours prior to scheduled surgery.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been
observed. If signs or symptoms occur, permanently discontinue treatment.
Monitor for proteinuria before initiation of, and periodically
throughout, treatment. For moderate to severe proteinuria, reduce the
dose or temporarily interrupt treatment.
Liver enzyme elevation has been observed during treatment with INLYTA.
Monitor ALT, AST and bilirubin before initiation of, and periodically
throughout, treatment.
For patients with moderate hepatic impairment, the starting dose should
be decreased. INLYTA has not been studied in patients with severe
hepatic impairment.
Women of childbearing potential should be advised of the potential
hazard to the fetus and to avoid becoming pregnant while receiving
INLYTA.
The most common (≥20%) adverse reactions are diarrhea, hypertension,
fatigue, decreased appetite, nausea, dysphonia, palmar-plantar
erythrodysesthesia (hand-foot) syndrome, weight decreased, vomiting,
asthenia, and constipation.
The most common (≥20%) lab abnormalities occurring in patients receiving
INLYTA (all grades, vs sorafenib) included increased creatinine,
decreased bicarbonate, hypocalcemia, decreased hemoglobin, decreased
lymphocytes (absolute), increased ALP, hyperglycemia, increased lipase,
increased amylase, increased ALT, and increased AST.
INLYTA is indicated for the treatment of advanced renal cell carcinoma
(RCC) after failure of one prior systemic therapy.
For more information on INLYTA and Pfizer Oncology, including Full
Prescribing Information, please visit www.pfizer.com.
About SUTENT® (sunitinib malate)
SUTENT is an oral multi-kinase inhibitor that works by blocking multiple
molecular targets implicated in the growth, proliferation and spread of
cancer. SUTENT was approved in 2006 and is indicated for the treatment
of advanced/metastatic renal cell carcinoma.
Selected Safety Information for SUTENT®
(sunitinib malate)
Boxed Warning/Hepatotoxicity: Hepatotoxicity has been observed in
clinical trials and post-marketing experience. This hepatotoxicity may
be severe, and deaths have been reported. Monitor liver function
tests before initiation of treatment, during each cycle of treatment,
and as clinically indicated. SUTENT should be interrupted for Grade 3 or
4 drug-related hepatic adverse events and discontinued if there is no
resolution. Do not restart SUTENT if patients subsequently experience
severe changes in liver function tests or have other signs and symptoms
of liver failure.
Women of childbearing potential should be advised of the potential
hazard to the fetus and to avoid becoming pregnant.
Given the potential for serious adverse reactions (ARs) in nursing
infants, a decision should be made whether to discontinue nursing or
SUTENT.
Cardiovascular events, including heart failure, cardiomyopathy,
myocardial ischemia, and myocardial infarction, some of which were
fatal, have been reported. Use SUTENT with caution in patients who are
at risk for, or who have a history of, these events. Monitor patients
for signs and symptoms of congestive heart failure (CHF) and, in the
presence of clinical manifestations, discontinuation is recommended.
Patients who presented with cardiac events, pulmonary embolism, or
cerebrovascular events within the previous 12 months were excluded from
clinical studies.
SUTENT has been shown to prolong QT interval in a dose-dependent manner,
which may lead to an increased risk for ventricular arrhythmias
including Torsades de Pointes, which has been seen in <0.1% of patients.
Monitoring with on-treatment electrocardiograms and electrolytes should
be considered.
Hypertension may occur. Monitor blood pressure and treat as needed with
standard antihypertensive therapy. In cases of severe hypertension,
temporary suspension of SUTENT is recommended until hypertension is
controlled.
There have been (<1%) reports, some fatal, of subjects presenting with
seizures and radiological evidence of reversible posterior
leukoencephalopathy syndrome (RPLS).
Hemorrhagic events, including tumor-related hemorrhage such as pulmonary
hemorrhage, have occurred. Some of these events were fatal. Perform
serial complete blood counts (CBCs) and physical examinations.
Cases of Tumor Lysis Syndrome (TLS) have been reported primarily in
patients with high tumor burden. Monitor these patients closely and
treat as clinically indicated.
Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic
purpura and hemolytic uremic syndrome, sometimes leading to renal
failure or a fatal outcome, has been reported in patients who received
SUTENT as monotherapy and in combination with bevacizumab. Discontinue
SUTENT in patients developing TMA. Reversal of the effects of TMA has
been observed after treatment was discontinued.
Proteinuria and nephrotic syndrome have been reported. Some of these
cases have resulted in renal failure and fatal outcomes. Perform
baseline and periodic urinalysis during treatment, with follow-up
measurement of 24-hour urine protein as clinically indicated. Interrupt
SUTENT and dose-reduce if 24-hour urine protein is ≥3 g; discontinue
SUTENT in cases of nephrotic syndrome or repeat episodes of urine
protein ≥3 g despite dose reductions.
Severe cutaneous reactions have been reported, including cases of
erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic
epidermal necrolysis (TEN), some of which were fatal. If signs or
symptoms of EM, SJS, or TEN are present, SUTENT treatment should be
discontinued. If a diagnosis of SJS or TEN is suspected, treatment must
not be re-started. Necrotizing fasciitis, including fatal cases, has
been reported, including of the perineum and secondary to fistula
formation. Discontinue SUTENT in patients who develop necrotizing
fasciitis.
SUTENT has been associated with symptomatic hypoglycemia, which may
result in loss of consciousness or require hospitalization. Reductions
in blood glucose levels may be worse in patients with diabetes. Check
blood glucose levels regularly during and after discontinuation of
SUTENT. Assess whether antidiabetic drug dosage needs to be adjusted to
minimize the risk of hypoglycemia.
The most common adverse reactions (≥20%) are fatigue, asthenia, fever,
diarrhea, nausea, mucositis/stomatitis, vomiting, dyspepsia, abdominal
pain, constipation, hypertension, peripheral edema, rash, hand-foot
syndrome, skin discoloration, dry skin, hair color changes, altered
taste, headache, back pain, arthralgia, extremity pain, cough, dyspnea,
anorexia, and bleeding.
For more information on SUTENT and Pfizer Oncology, including Full
Prescribing Information, including Boxed warning, please visit www.pfizer.com.
Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New
York, US
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany,
and Pfizer Inc. The global strategic alliance between Merck KGaA,
Darmstadt, Germany, and Pfizer Inc., New York, US, enables the companies
to benefit from each other’s strengths and capabilities and further
explore the therapeutic potential of avelumab, an investigational
anti-PD-L1 antibody initially discovered and developed by Merck KGaA,
Darmstadt, Germany. The immuno-oncology alliance will jointly develop
and commercialize avelumab and advance Pfizer’s PD-1 antibody. The
alliance is focused on developing high-priority international clinical
programs to investigate avelumab as a monotherapy, as well as in
combination regimens, and is striving to find new ways to treat cancer.
Pfizer Inc.: Working together for a healthier world™
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 healthcare products. Our global portfolio
includes medicines and vaccines as well as many of the world's
best-known consumer healthcare products. 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, Pfizer has worked to make a difference for all who
rely on us. For more information, please visit us at www.pfizer.com. In
addition, to learn more, follow us on Twitter at @Pfizer
and @Pfizer_News,
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and like us on Facebook at Facebook.com/Pfizer.
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Merck KGaA, Darmstadt, Germany
Merck KGAA, Darmstadt, Germany, is a leading science and technology
company in healthcare, life science and performance materials. Around
50,000 employees work to further develop technologies that improve and
enhance life – from biopharmaceutical therapies to treat cancer or
multiple sclerosis, cutting-edge systems for scientific research and
production, to liquid crystals for smartphones and LCD televisions. In
2015, Merck KGaA, Darmstadt, Germany, generated sales of € 12.85 billion
in 66 countries.
Founded in 1668, Merck KGaA, Darmstadt, Germany, is the world's oldest
pharmaceutical and chemical company. The founding family remains the
majority owner of the publicly listed corporate group. Merck KGaA,
Darmstadt, Germany, holds the global rights to the Merck KGaA,
Darmstadt, Germany, name and brand. The only exceptions are the United
States and Canada, where the company operates as EMD Serono,
MilliporeSigma and EMD Performance Materials.
Pfizer Disclosure Notice
The information contained in this release is as of April 5, 2016.
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 avelumab
(MSB0010718C), including a potential indication for avelumab in
combination with axitinib for the treatment of advanced renal cell
carcinoma, Pfizer’s and Merck KGaA, Darmstadt, Germany’s immuno-oncology
alliance involving anti-PD-L1 and anti-PD-1 therapies, 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, the uncertainties
inherent in research and development, including the ability to meet
anticipated clinical study commencement and completion dates as well as
the possibility of unfavorable study results; risks associated with
interim data; the risk that clinical trial data are subject to differing
interpretations, and, even when we view data as sufficient to support
the safety and/or effectiveness of a product candidate, regulatory
authorities may not share our views and may require additional data or
may deny approval altogether; whether and when drug applications may be
filed in any jurisdictions for any potential indications for avelumab,
combination therapies or other product candidates; whether and when any
such applications may be approved by regulatory authorities, which will
depend on the assessment by such regulatory authorities of the
benefit-risk profile suggested by the totality of the efficacy and
safety information submitted; decisions by regulatory authorities
regarding labeling and other matters that could affect the availability
or commercial potential of avelumab, combination therapies or other
product candidates; 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, 2015, 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.
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