BAVENCIO® (avelumab) Plus INLYTA® (axitinib) Significantly Improved Progression-Free Survival in Previously Untreated Patients With Advanced Renal Cell Carcinoma in Phase III Study

Darmstadt, Germany and New York (ots/PRNewswire) -

Not intended for US, Canada and UK-based media

- First positive Phase III immunotherapy trial in combination with
a tyrosine kinase inhibitor (TKI) in any tumor type
- Results significant in both PDL1+ and all-comer populations
- Alliance plans to pursue a regulatory submission in the US and
discussions with other health authorities based on interim results
for progression-free survival
- Trial will continue for the other primary endpoint of overall
survival; detailed results to be submitted for presentation at an
upcoming medical congress

Merck and Pfizer Inc. (NYSE: PFE) today announced positive
top-line results from the pivotal Phase III JAVELIN Renal 101 study
evaluating BAVENCIO® (avelumab)* in combination with INLYTA®
(axitinib)*, compared with SUTENT® (sunitinib) as initial therapy for
patients with advanced renal cell carcinoma (RCC). As part of a
planned interim analysis, an independent Data Monitoring Committee
confirmed that the trial showed a statistically significant
improvement in progression-free survival (PFS) by central review for
patients treated with the combination whose tumors had programmed
death ligand-1-positive (PD-L1+) expression greater than 1% (primary
objective), as well as in the entire study population regardless of
PD-L1 tumor expression (secondary objective). According to the
statistical analysis plan, if PFS was statistically significant in
the PD-L1+ subgroup, then PFS in the entire study population was to
be analyzed for statistical significance. JAVELIN Renal 101 will
continue as planned to the final analysis for the other primary
endpoint of overall survival (OS). No new safety signals were
observed, and adverse events for BAVENCIO, INLYTA and SUTENT in this
trial were consistent with the known safety profiles for all three
medicines. The alliance intends to pursue a regulatory submission in
the US based on these interim results, and these results will be
discussed with global health authorities. A detailed analysis will
also be submitted for presentation at an upcoming medical congress.

"JAVELIN Renal 101 is the first positive Phase III study combining
an immune checkpoint blocker with a TKI, supporting the potential of
BAVENCIO and INLYTA as a new cancer treatment approach for patients
with advanced RCC," said Chris Boshoff, M.D., Ph.D., Senior Vice
President and Head of Immuno-Oncology, Early Development and
Translational Oncology, Pfizer Global Product Development. "These
positive results reinforce Pfizer's long-standing heritage in
advancing standards of care for people with RCC, and we look forward
to discussing these data in greater detail with health authorities."

In December 2017, the US Food and Drug Administration (FDA)
granted Breakthrough Therapy Designation for BAVENCIO in combination
with INLYTA for treatment-naïve patients with advanced RCC. Despite
available therapies, the outlook for patients with advanced RCC
remains poor.[1] Approximately 20% to 30% of patients are first
diagnosed at the metastatic stage.[2] The five-year survival rate for
patients with metastatic RCC is approximately 12%.[1]

"We are encouraged by these data which illustrate the impact of
BAVENCIO in combination with INLYTA as a potential first-line
treatment for people with advanced RCC, a serious and
life-threatening cancer," said Luciano Rossetti, M.D., Executive Vice
President, Global Head of Research & Development at the Biopharma
business of Merck. "They also support our firm belief in the promise
of combining BAVENCIO with currently approved therapies and novel
agents, a strong focus of the overall JAVELIN clinical development
program."

JAVELIN Renal 101 is a global Phase III, multicenter, randomized
(1:1) study investigating the efficacy and safety of BAVENCIO in
combination with INLYTA as a first-line treatment option compared
with SUTENT monotherapy in 886 patients with advanced RCC across all
risk groups. The primary objectives are to demonstrate that BAVENCIO
in combination with INLYTA is superior to SUTENT monotherapy in
prolonging PFS or OS in patients with PD-L1+ tumors. BAVENCIO was
administered at 10 mg/kg IV every two weeks in combination with
INLYTA at 5 mg orally twice daily; SUTENT was administered at 50 mg
orally once daily, four weeks on/two weeks off.

*The combination of BAVENCIO and INLYTA is under clinical
investigation for advanced RCC, and there is no guarantee this
combination will be approved for advanced RCC by any health authority
worldwide. In the US, INLYTA is approved as monotherapy for the
treatment of advanced RCC after failure of one prior systemic
therapy. INLYTA is also approved by the European Medicines Agency
(EMA) for use in the EU in adult patients with advanced RCC after
failure of prior treatment with SUTENT or a cytokine.

About the JAVELIN Clinical Development Program

The clinical development program for BAVENCIO, known as JAVELIN,
involves at least 30 clinical programs, eight Phase III trials and
more than 8,600 patients evaluated across more than 15 different
tumor types. In addition to RCC, these tumor types include breast,
gastric/gastro-esophageal junction, head and neck, Hodgkin's
lymphoma, melanoma, mesothelioma, Merkel cell carcinoma, non-small
cell lung cancer, ovarian and urothelial carcinoma.

About Renal Cell Carcinoma

RCC is the most common form of kidney cancer, accounting for about
2% to 3% of all cancers in adults.[3],[4] The most common type of RCC
is clear cell carcinoma, accounting for approximately 70% of all
cases.[3] In 2012, there were approximately 338,000 new cases of RCC
diagnosed worldwide, with an estimated 63,340 cases expected in the
US alone in 2018.[3],[5] Incidence varies substantially worldwide,
with generally higher rates seen in North America and Central/Eastern
Europe.[5]

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.[6]-[8] BAVENCIO has also been shown
to induce NK cell-mediated direct tumor cell lysis via
antibody-dependent cell-mediated cytotoxicity (ADCC) in
vitro.[8]-[10] In November 2014, Merck and Pfizer announced a
strategic alliance to co-develop and co-commercialize BAVENCIO.

Approved Indications

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.

BAVENCIO is also approved by the European Medicines Agency (EMA)
for use in the EU as a monotherapy for the treatment of adult
patients with mMCC.

Important Safety Information from the US FDA Approved Label

The warnings and precautions for BAVENCIO include immune-mediated
adverse reactions (such as pneumonitis, hepatitis, colitis,
endocrinopathies, nephritis and renal dysfunction, and other adverse
reactions), infusion-related reactions and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in
patients treated with BAVENCIO for mMCC and patients with locally
advanced or mUC include fatigue, musculoskeletal pain, diarrhea,
nausea, infusion-related reaction, peripheral edema, decreased
appetite/hypophagia, urinary tract infection and rash.

About INLYTA® (axitinib)

INLYTA 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). In the US, INLYTA is approved for the treatment of advanced
renal cell carcinoma (RCC) after failure of one prior systemic
therapy. INLYTA is also approved by the European Medicines Agency
(EMA) for use in the EU in adult patients with advanced RCC after
failure of prior treatment with sunitinib or a cytokine.

INLYTA Important Safety Information

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 antihypertensive medications, reduce the
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 or
who have a history of 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.

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 potential
hazard to the fetus and to avoid becoming pregnant while receiving
INLYTA.

Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the dose.
Grapefruit or grapefruit juice may also increase INLYTA plasma
concentrations and should be avoided.

Avoid strong CYP3A4/5 inducers and, if possible, avoid moderate
CYP3A4/5 inducers.

The most common (>=20%) adverse events (AEs) occurring in patients
receiving INLYTA (all grades, vs sorafenib) were diarrhea (55% vs
53%), hypertension (40% vs 29%), fatigue (39% vs 32%), decreased
appetite (34% vs 29%), nausea (32% vs 22%), dysphonia (31% vs 14%),
hand-foot syndrome (27% vs 51%), weight decreased (25% vs 21%),
vomiting (24% vs 17%), asthenia (21% vs 14%), and constipation (20%
vs 20%).

The most common (>=10%) grade 3/4 AEs occurring in patients
receiving INLYTA (vs sorafenib) were hypertension (16% vs 11%),
diarrhea (11% vs 7%), and fatigue (11% vs 5%).

The most common (>=20%) lab abnormalities occurring in patients
receiving INLYTA (all grades, vs sorafenib) included increased
creatinine (55% vs 41%), decreased bicarbonate (44% vs 43%),
hypocalcemia (39% vs 59%), decreased hemoglobin (35% vs 52%),
decreased lymphocytes (absolute) (33% vs 36%), increased ALP (30% vs
34%), hyperglycemia (28% vs 23%), increased lipase (27% vs 46%),
increased amylase (25% vs 33%), increased ALT (22% vs 22%), and
increased AST (20% vs 25%).

For more information and full Prescribing Information, visit
http://www.INLYTA.com.

SUTENT Important Safety Information

Boxed Warning/Hepatotoxicity has been observed in clinical trials
and postmarketing experience. Hepatotoxicity may be severe, and in
some cases fatal. Monitor hepatic function and interrupt, reduce, or
discontinue dosing as recommended. Fatal liver failure has been
observed. Monitor liver function tests before initiation of
treatment, during each cycle of treatment, and as clinically
indicated. Interrupt SUTENT for Grade 3 or 4 drug-related hepatic
adverse reactions and discontinue if there is no resolution. Do not
restart SUTENT if patients subsequently experience severe changes in
liver function tests or have signs and symptoms of liver failure.

Cardiovascular events, including myocardial ischemia, myocardial
infarction, left ventricular ejection fraction declines to below the
lower limit of normal and cardiac failure including death have
occurred. Monitor patients for signs and symptoms of congestive heart
failure. Discontinue SUTENT for clinical manifestations of congestive
heart failure. In patients without cardiac risk factors, a baseline
evaluation of ejection fraction should be considered. Baseline and
periodic evaluations of left ventricular ejection fraction should
also be considered while these patients are receiving SUTENT.

SUTENT can cause QT Prolongation 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.
Monitor patients that are at a higher risk for developing QT interval
prolongation, including those with a history of QT interval
prolongation, patients who are taking antiarrhythmics, or patients
with relevant pre-existing cardiac disease, bradycardia, or
electrolyte disturbances. Consider monitoring of electrocardiograms
and electrolytes. Concomitant treatment with strong CYP3A4 inhibitors
may increase sunitinib plasma concentrations and dose reduction of
SUTENT 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.

Hemorrhagic events, including tumor-related hemorrhage, and viscus
perforation (both with fatal events) have occurred. These events may
occur suddenly, and in the case of pulmonary tumors, may present as
severe and life-threatening hemoptysis or pulmonary hemorrhage.
Perform serial complete blood counts (CBCs) and physical
examinations.

Cases of tumor lysis syndrome (TLS) (some fatal) have been
reported. Patients generally at risk of TLS are those with high tumor
burden prior to treatment. 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.
Monitor patients for the development or worsening of proteinuria.
Perform baseline and periodic urinalysis during treatment, with
follow-up measurement of 24-hour urine protein as clinically
indicated. Interrupt treatment for 24-hour urine protein >=3 grams.
Discontinue for repeat episodes of protein >=3 grams despite dose
reductions or nephrotic syndrome.

Dermatologic toxicities: Severe cutaneous reactions have been
reported, including cases of necrotizing fasciitis, 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, discontinue SUTENT treatment. If a
diagnosis of SJS or TEN is suspected, treatment must not be
restarted.

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.

Thyroid dysfunction may occur. Monitor thyroid function in
patients with signs and/or symptoms suggestive of thyroid
dysfunction, including hypothyroidism, hyperthyroidism, and
thyroiditis, and treat per standard medical practice.

Hypoglycemia may occur. SUTENT can result in symptomatic
hypoglycemia, which may lead to a 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 treatment with SUTENT. Assess if
antidiabetic drug dosage needs to be adjusted to minimize the risk of
hypoglycemia.

Osteonecrosis of the jaw (ONJ) has been reported. Consider
preventive dentistry prior to treatment with SUTENT. If possible,
avoid invasive dental procedures, particularly in patients receiving
intravenous bisphosphonate therapy.

Impaired wound healing has occurred with SUTENT. Temporary
interruption of therapy with SUTENT is recommended in patients
undergoing major surgical procedures. There is limited clinical
experience regarding the timing of reinitiation of therapy following
major surgical intervention. Therefore, the decision to resume SUTENT
therapy following a major surgical intervention should be based upon
clinical judgment of recovery from surgery.

Embryo fetal toxicity and reproductive potential

Females - SUTENT can cause fetal harm when administered to
pregnant women. Advise pregnant women of the potential risk to a
fetus. Advise females of reproductive potential to use effective
contraception during treatment with SUTENT and for 4 weeks following
the final dose.

Males - Based on findings in animal reproduction studies, advise
male patients with female partners of reproductive potential to use
effective contraception during treatment with SUTENT and for 7 weeks
after the last dose.

Male and female infertility - based on findings in animals, male
and female fertility may be compromised by treatment with SUTENT

Lactation: Because of the potential for serious adverse reactions
in breastfed infants from SUTENT, advise a lactating woman not to
breastfeed during treatment with SUTENT and for at least 4 weeks
after the last dose.

Venous thromboembolic events: In patients treated with SUTENT
(N=7527) for GIST, advanced RCC, adjuvant treatment of RCC and pNET,
3.5% of patients experienced a venous thromboembolic event; 2.2%
Grade 3-4.

There have been (<1%) reports, some fatal, of subjects presenting
with seizures and radiological evidence of reversible posterior
leukoencephalopathy syndrome (RPLS). Patients with seizures and
signs/symptoms consistent with RPLS, such as hypertension, headache,
decreased alertness, altered mental functioning, and visual loss,
including cortical blindness, should be controlled with medical
management including control of hypertension. Temporary suspension of
SUTENT is recommended; following resolution, treatment may be resumed
at the discretion of the treating healthcare provider.

Pancreatic function: In a trial of patients receiving adjuvant
treatment for RCC, 1 patient (<1%) on SUTENT and none on placebo
experienced pancreatitis.

CYP3A4 inhibitors and inducers: Dose adjustments are recommended
when SUTENT is administered with CYP3A4 inhibitors or inducers.
During treatment with SUTENT, patients should not drink grapefruit
juice, eat grapefruit, or take St. John's Wort.

Most common ARs & most common grade 3/4 ARs (adjuvant RCC): The
most common ARs reported in >=20% of patients receiving SUTENT for
adjuvant treatment of RCC and more commonly than in patients given
placebo (all grades, vs placebo) were mucositis/stomatitis (61% vs
15%), diarrhea (57% vs 22%), fatigue/asthenia (57% vs 34%), hand-foot
syndrome (50% vs 10%), hypertension (39% vs 14%), altered taste (38%
vs 6%), nausea (34% vs 15%), dyspepsia (27% vs 7%), abdominal pain
(25% vs 9%), hypothyroidism/TSH increased (24% vs 4%), rash (24% vs
12%), hair color changes (22% vs 2%). The most common grade 3/4 ARs
reported in >=5% of patients receiving SUTENT for adjuvant treatment
of RCC and more commonly than in patients given placebo (vs placebo)
were hand-foot syndrome (16% vs <1%), fatigue/asthenia (8% vs 2%),
hypertension (8% vs 1%), and mucositis/stomatitis (6% vs 0%).

Most common grade 3/4 lab abnormalities (adjuvant RCC): The most
common grade 3/4 lab abnormalities (occurring in >= 2% of patients
receiving SUTENT) included neutropenia (13%), thrombocytopenia (5%),
leukopenia (3%), lymphopenia (3%), elevated alanine aminotransferase
(2%), elevated aspartate aminotransferase (2%), hyperglycemia (2%),
and hyperkalemia (2%).

Most common ARs & most common grade 3/4 ARs (advanced RCC): The
most common ARs reported in >=20% of patients receiving SUTENT for
treatment-naïve metastatic RCC (all grades, vs IFN?) were diarrhea
(66% vs 21%), fatigue (62% vs 56%), nausea (58% vs 41%), anorexia
(48% vs 42%), altered taste (47% vs 15%), mucositis/stomatitis (47%
vs 5%), pain in extremity/limb discomfort (40% vs 30%), vomiting (39%
vs 17%), bleeding, all sites (37% vs 10%), hypertension (34% vs 4%),
dyspepsia (34% vs 4%), arthralgia (30% vs 19%), abdominal pain (30%
vs 12%), rash (29% vs 11%), hand-foot syndrome (29% vs 1%), back pain
(28% vs 14%), cough (27% vs 14%), asthenia (26% vs 22%), dyspnea (26%
vs 20%), skin discoloration/yellow skin (25% vs 0%), peripheral edema
(24% vs 5%), headache (23% vs 19%), constipation (23% vs 14%), dry
skin (23% vs 7%), fever (22% vs 37%), and hair color changes (20% vs
<1%). The most common grade 3/4 ARs reported in >=5% of patients with
RCC receiving SUTENT (vs IFN?) were fatigue (15% vs 15%),
hypertension (13% vs <1%), asthenia (11% vs 6%), diarrhea (10% vs
<1%), hand-foot syndrome (8% vs 0%), dyspnea (6% vs 4%), nausea (6%
vs 2%), back pain (5% vs 2%), pain in extremity/limb discomfort (5%
vs 2%), vomiting (5% vs 1%), and abdominal pain (5% vs 1%).

Most common grade 3/4 lab abnormalities (advanced RCC): The most
common grade 3/4 lab abnormalities (occurring in >=5% of patients
with RCC receiving SUTENT vs IFN?) included lymphocytes (18% vs 26%),
lipase (18% vs 8%), neutrophils (17% vs 9%), uric acid (14% vs 8%),
platelets (9% vs 1%), hemoglobin (8% vs 5%), sodium decreased (8% vs
4%), leukocytes (8% vs 2%), glucose increased (6% vs 6%), phosphorus
(6% vs 6%), and amylase (6% vs 3%).

Most common ARs & most common grade 3/4 ARs (imatinib-resistant or
-intolerant GIST): The most common ARs reported in >=20% of patients
with GIST and more commonly with SUTENT than placebo (all grades, vs
placebo) were diarrhea (40% vs 27%), anorexia (33% vs 29%), skin
discoloration (30% vs 23%), mucositis/stomatitis (29% vs 18%),
asthenia (22% vs 11%), altered taste (21% vs 12%), and constipation
(20% vs 14%). The most common grade 3/4 ARs reported in >=4% of
patients with GIST receiving SUTENT (vs placebo) were asthenia (5% vs
3%), hand-foot syndrome (4% vs 3%), diarrhea (4% vs 0%), and
hypertension (4% vs0%).

Most common grade 3/4 lab abnormalities (imatinib-resistant or -
intolerant GIST): The most common grade 3/4 lab abnormalities
(occurring in >=5% of patients with GIST receiving SUTENT vs placebo)
included lipase (10% vs 7%), neutrophils (10% vs 0%), amylase (5% vs
3%), and platelets (5% vs 0%).

Most common ARs & most common grade 3/4 ARs (advanced pNET): The
most common ARs reported in >=20% of patients with advanced pNET and
more commonly with SUTENT than placebo (all grades, vs placebo) were
diarrhea (59% vs 39%), stomatitis/oral syndromes (48% vs 18%), nausea
(45% vs 29%), abdominal pain (39% vs 34%), vomiting (34% vs 31%),
asthenia (34% vs 27%), fatigue (33% vs 27%), hair color changes (29%
vs 1%), hypertension (27% vs 5%), hand-foot syndrome (23% vs 2%),
bleeding events (22% vs 10%), epistaxis (21% vs 5%), and dysgeusia
(21% vs 5%). The most common grade 3/4 ARs reported in >=5% of
patients with advanced pNET receiving SUTENT (vs placebo) were
hypertension (10% vs 1%), hand-foot syndrome (6% vs 0%),
stomatitis/oral syndromes (6% vs 0%), abdominal pain (5% vs 10%),
fatigue (5% vs 9%), asthenia (5% vs 4%), and diarrhea (5% vs 2%).

Most common grade 3/4 lab abnormalities (advanced pNET): The most
common grade 3/4 lab abnormalities (occurring in >=5% of patients
with advanced pNET receiving SUTENT vs placebo) included decreased
neutrophils (16% vs 0%), increased glucose (12% vs 18%), increased
alkaline phosphatase (10% vs 11%), decreased phosphorus (7% vs 5%),
decreased lymphocytes (7% vs 4%), increased creatinine (5% vs 5%),
increased lipase (5% vs 4%), increased AST (5% vs 3%), and decreased
platelets (5% vs 0%).

Please see full Prescribing Information, including BOXED WARNING
and Medication Guide, for SUTENT® (sunitinib malate) at
http://www.SUTENT.com.

About SUTENT® (sunitinib malate)

Sunitinib is a small molecule that inhibits multiple receptor
tyrosine kinases, some of which are implicated in tumor growth,
pathologic angiogenesis, and metastatic progression of cancer.
Sunitinib was evaluated for its inhibitory activity against a variety
of kinases (>80 kinases) and was identified as an inhibitor of
platelet-derived growth factor receptors (PDGFR? and PDGFR?),
vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and
VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3
(FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the
glial cell-line derived neurotrophic factor receptor (RET).

SUTENT is indicated in the US for the treatment of
gastrointestinal stromal tumor (GIST) after disease progression on or
intolerance to imatinib mesylate; the treatment of advanced renal
cell carcinoma (RCC); the adjuvant treatment of adult patients at
high risk of recurrent RCC following nephrectomy; the treatment of
progressive, well-differentiated pancreatic neuroendocrine tumors
(pNET) in patients with unresectable locally advanced or metastatic
disease.

About Merck-Pfizer Alliance

Immuno-oncology is a top priority for Merck and Pfizer. The global
strategic alliance between Merck and Pfizer enables the companies to
benefit from each other's strengths and capabilities and further
explore the therapeutic potential of BAVENCIO (avelumab), an
anti-PD-L1 antibody initially discovered and developed by Merck. The
immuno-oncology alliance is jointly developing and commercializing
BAVENCIO and advancing Pfizer's PD-1 antibody. 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 Press Releases are distributed by e-mail at the same
time they become available on the Merck Website. Please go to
http://www.merckgroup.com/subscribe to register online, change your
selection or discontinue this service.

About Merck

Merck is a leading science and technology company in healthcare,
life science and performance materials. Almost 53,000 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 2017, Merck
generated sales of EUR 15.3 billion in 66 countries.

Founded in 1668, Merck is the world's oldest pharmaceutical and
chemical company. The founding family remains the majority owner of
the publicly listed corporate group. Merck, Darmstadt, Germany holds
the global rights to the "Merck" name and brand except in the United
States and Canada, where the company operates as EMD Serono,
MilliporeSigma and EMD Performance Materials.

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 health care products.
Our global portfolio includes medicines and vaccines as well as many
of the world's best-known consumer health care 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, 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
http://www.pfizer.com. In addition, to learn more, please visit us on
http://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 September 11,
2018. 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), including a potential new indication for BAVENCIO in
combination with INLYTA (axitinib) for the treatment of patients with
advanced renal cell carcinoma (the "Potential Indication"), the
Merck-Pfizer 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, uncertainties regarding the commercial success of BAVENCIO;
the uncertainties inherent in research and development, including the
ability to meet anticipated clinical study commencement and
completion dates and regulatory submission dates, as well as the
possibility of unfavorable study results, including unfavorable new
clinical data and additional analyses of existing clinical data and
uncertainties regarding whether the other primary endpoint of JAVELIN
Renal 101 will be met; 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 regulatory authorities will be satisfied
with the design of and results from our clinical studies; whether and
when any drug applications may be filed for BAVENCIO in any
jurisdictions for the Potential Indication or for any other potential
indications for BAVENCIO, combination therapies or other product
candidates; whether and when regulatory authorities in any
jurisdictions where applications are pending or may be submitted for
BAVENCIO, combination therapies or other product candidates may
approve any such applications, 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
BAVENCIO, combination therapies or other product candidates,
including the Potential Indication 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, 2017, 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 http://www.sec.gov and http://www.pfizer.com.

References

1. National Cancer Institute: SEER Stat Fact Sheets: Kidney and
renal pelvis. Available from:
http://seer.cancer.gov/statfacts/html/kidrp.html. Accessed July
2018.
2. Ljungberg B, Campbell S and Cho H. The Epidemiology of Renal Cell
Carcinoma. Eur Urol. 2011;60:615-621.
3. American Cancer Society. What is kidney cancer? Available from:
https://www.cancer.org/cancer/kidney-cancer/about.html. Accessed
July 2018.
4. Escudier B, Porta C, Schmidinger M et al Renal cell carcinoma:
ESMO clinical practice guidelines for diagnosis, treatment and
follow-up. Annal Oncol. 2014; 25(Suppl3):iii49-iii56.
5. World Cancer Research Fund International: Kidney cancer
statistics. Available from: http://www.wcrf.org/int/cancer-facts-
figures/data-specific-cancers/kidney-cancer-statistics. Accessed
July 2018.
6. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the
landscape of cancer immunotherapy. Cancer Control.
2014;21(3):231-237.
7. Dahan R, Sega E, Engelhardt J, Selby M, Korman AJ, Ravetch JV.
Fc?Rs modulate the anti-tumor activity of antibodies targeting
the PD-1/PD-L1 axis. Cancer Cell. 2015;28(3):285-295.
8. 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.
9. Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to
enhance antitumor ADCC. Immunotherapy. 2012;4(5):511-527.
10. Hamilton G, Rath B. Avelumab: combining immune checkpoint
inhibition and antibody-dependent cytotoxicity. Expert Opin Biol
Ther. 2017;17(4):515-523.

Merck

Media Friederike Segeberg +49-6151-72-6328

Investor Relations +49-6151-72-3321

Pfizer

Media (US) Jessica Smith +1-212-733-6213

Investor Relations Ryan Crowe +1-212-733-8160

(Logo:
http://mma.prnewswire.com/media/611425/Merck_Pfizer_Logo.jpg )

ots Originaltext: Merck KGaA
Im Internet recherchierbar: http://www.presseportal.de

Original-Content von: Merck KGaA, übermittelt durch news aktuell