DARMSTADT, Germany and
NEW YORK, February 15, 2018 /PRNewswire/ --
Merck KGaA, Darmstadt, Germany,
and Pfizer Inc. (NYSE: PFE) today announced results from the Phase
III JAVELIN Lung 200 trial comparing avelumab* to docetaxel in
patients with unresectable, recurrent or metastatic non-small cell
lung cancer (NSCLC) whose disease progressed after treatment with a
platinum-containing doublet therapy. While the trial did not meet
its prespecified endpoint of improving overall survival (OS) in
patients with programmed death ligand-1-positive (PD-L1+) (1% or
higher) tumors (HR: 0.90 [96% CI: 0.72-1.12], p-value 0.1627,
one-sided), the proportion of patients in the chemotherapy arm
crossing over to immune checkpoint inhibitors outside the study was
higher than previously reported in post-platinum immunotherapy
clinical trials, and this may have confounded this trial outcome
(percentage of patients receiving subsequent checkpoint inhibitor
therapy: docetaxel arm 26.4%; avelumab arm 5.7%).
(Logo:
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)
However, improvements in OS versus the control arm were observed
in the moderate-to-high PD-L1+ expression (50% or greater, which
represented approximately 40% of the study population) and high
PD-L1+ expression population (PD-L1+ expression 80% or greater,
which represented approximately 30% of the study population) (HR:
0.67 [95% CI: 0.51-0.89], p-value 0.0052, two-sided; and HR
0.59 [95% CI: 0.42-0.83], p-value 0.0022, two-sided,
respectively**). The safety profile for avelumab in this
trial was consistent with that observed in the overall JAVELIN
clinical development program; no new safety signals were
identified.
"Avelumab performed in line with expectations in the trial from
both an efficacy and safety perspective," said primary investigator
Fabrice Barlesi, M.D., Ph.D., Head
of Multidisciplinary Oncology and Therapeutic Innovations
Department at Aix-Marseille University and the Assistance Publique
Hôpitaux de Marseille, France.
"With immune checkpoint inhibitors approved for patients with
previously treated, advanced non-small cell lung cancer, higher
percentages of immunotherapy-naïve patients are receiving
subsequent checkpoint inhibitors in their progressive treatments.
This was observed in the JAVELIN Lung 200 control arm and may have
confounded the primary outcome of the study."
"Avelumab's overall clinical activity in this study supports its
profile with expected efficacy across several endpoints and
subgroups," said Luciano Rossetti,
M.D., Executive Vice President, Global Head of Research &
Development at the Biopharma business of Merck KGaA, Darmstadt,
Germany, which operates as EMD
Serono in the US and Canada.
"However, the chemotherapy group displayed improved overall
survival compared with previous PDx trials, most likely due to the
impact of crossover to other checkpoint inhibitors."
"We are committed to understanding the data in the context of
the subpopulations and the impact of access to other immune
checkpoint inhibitors," said Chris
Boshoff, M.D., Ph.D., Senior Vice President and Head of
Immuno-Oncology, Early Development and Translational Oncology,
Pfizer Global Product Development. "We will continue to progress
the broad avelumab program, exploring various indications."
Detailed results from the JAVELIN Lung 200 trial will be
submitted for presentation at an upcoming medical congress, and the
companies aim to share the data with regulatory agencies.
In 2017, avelumab first received accelerated
approval† by the US Food and Drug Administration (FDA)
for metastatic Merkel cell carcinoma (mMCC) and for previously
treated patients with locally advanced or metastatic urothelial
carcinoma (mUC), followed by the European Commission (EC) approval
for mMCC later that year.
The clinical development program for avelumab, known as JAVELIN,
involves at least 30 clinical programs and over 7,000 patients
evaluated across more than 15 different tumor types. In addition to
NSCLC, these cancers include breast, gastric/gastro-esophageal
junction, head and neck, Hodgkin's lymphoma, melanoma,
mesothelioma, Merkel cell carcinoma, ovarian, renal cell carcinoma
and urothelial carcinoma.
In December 2017, the FDA granted
Breakthrough Therapy Designation for avelumab as a combination
therapy for treatment-naïve patients with advanced renal cell
carcinoma.
*Avelumab is under clinical investigation for treatment of NSCLC
and has not been demonstrated to be safe and effective for this
indication. There is no guarantee that avelumab will be approved
for NSCLC by any health authority worldwide.
**When the primary endpoint is not met, statistical
significance cannot be formally claimed with the predefined
statistical significance level (i.e., 0.05 two-sided). In this
circumstance, the Type I error is not strictly controlled and
the p-value should be interpreted cautiously.
About JAVELIN Lung 200
JAVELIN Lung 200 is a Phase III, randomized, open-label,
multicenter trial investigating avelumab versus docetaxel in
patients with locally advanced unresectable, metastatic or
recurrent NSCLC whose disease has progressed after a
platinum-containing doublet chemotherapy. The trial included 792
patients from approximately 260 sites in North America, South
America, Asia, Africa, Australia and Europe. The primary objective was to
demonstrate superior OS compared with docetaxel in patients with
PD-L1+ unresectable, recurrent or metastatic NSCLC whose disease
progressed after treatment with a platinum-containing doublet
therapy.
About JAVELIN Lung Program
In addition to JAVELIN Lung 200, avelumab's lung cancer clinical
development program includes several other ongoing clinical trials
investigating avelumab alone and in combination. JAVELIN Lung 100
is a Phase III randomized open-label, multicenter trial to assess
the safety and efficacy of avelumab, compared with platinum-based
doublet chemotherapy, in patients with metastatic NSCLC who have
not previously received any systemic treatment for their NSCLC.
JAVELIN Lung 101 is a Phase Ib/II multicenter, international,
dose-finding trial designed to evaluate the safety and efficacy of
avelumab in combination with either Pfizer's crizotinib or
lorlatinib in patients with advanced or metastatic NSCLC. JAVELIN
Medley is a Phase Ib/II randomized open-label, multicenter
dose-finding trial of avelumab in combination with other immune
modulators in patients with selected locally advanced or metastatic
solid tumors, including NSCLC.
About Non-Small Cell Lung Cancer
Globally, lung cancer is the most common cause of cancer-related
deaths in men and the second most common in women,1
responsible for more deaths than colon, breast and prostate cancer
combined.2 NSCLC is the most common type of lung cancer,
accounting for 80 to 85% of all lung cancers.3 The
five-year survival rate for people diagnosed with lung cancer that
has spread (metastasized) to other areas of the body is
1%.4
About Avelumab
Avelumab is a human anti-programmed death ligand-1 (PD-L1)
antibody. Avelumab 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, avelumab has been shown
to release the suppression of the T cell-mediated antitumor immune
response in preclinical models.5-7
Avelumab has also been shown to induce NK cell-mediated direct
tumor cell lysis via antibody-dependent cell-mediated cytotoxicity
(ADCC) in vitro.7-9 In
November 2014, Merck KGaA, Darmstadt,
Germany, and Pfizer announced a
strategic alliance to co-develop and co-commercialize avelumab.
† Approved Indications in the US
The FDA granted accelerated approval for avelumab
(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.
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% (21/1738) 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 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 was reported
in 0.9% (16/1738) of patients, including two (0.1%) patients with
Grade 5, and 11 (0.6%) with Grade 3.
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, and
permanently discontinue for life-threatening (Grade 4) or recurrent
(Grade 3) colitis upon reinitiation of BAVENCIO. Immune-mediated
colitis occurred in 1.5% (26/1738) 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% (8/1738) 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% (98/1738) 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% (2/1738) 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% (1/1738) 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 1,738 patients treated with BAVENCIO:
myocarditis with fatal cases, myositis, psoriasis, arthritis,
exfoliative dermatitis, erythema multiforme, pemphigoid,
hypopituitarism, uveitis, Guillain-Barré syndrome, and systemic
inflammatory response.
BAVENCIO can cause severe (Grade 3) or life-threatening (Grade
4) infusion-related reactions. Patients should be
premedicated with an antihistamine and acetaminophen prior to the
first 4 infusions and for subsequent doses 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% (439/1738) of
patients, including three (0.2%) patients with Grade 4 and nine
(0.5%) with Grade 3.
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%).
Please see full US Prescribing Information and Medication Guide
available at www.BAVENCIO.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. 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 avelumab, an anti-PD-L1
antibody initially discovered and developed by Merck KGaA,
Darmstadt, Germany. The
immuno-oncology alliance is jointly developing and commercializing
avelumab and advancing 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 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 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 2016, Merck
KGaA, Darmstadt, Germany,
generated sales of € 15.0 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" name and brand except in the United States and Canada, where the company operates as EMD
Serono, MilliporeSigma and EMD Performance Materials.
About EMD Serono, Inc.
EMD Serono is the biopharmaceutical business of Merck KGaA,
Darmstadt, Germany - a leading
science and technology company - in the US and Canada focused exclusively on specialty care.
For more than 40 years, the business has integrated cutting-edge
science, innovative products and industry-leading patient support
and access programs. EMD Serono has deep expertise in neurology,
fertility and endocrinology, as well as a robust pipeline of
potential therapies in oncology, immuno-oncology and immunology as
R&D focus areas. Today, the business has 1,200 employees around
the country with commercial, clinical and research operations based
in the company's home state of Massachusetts.
www.emdserono.com
About Pfizer: 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
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Pfizer Disclosure Notice
The information contained in this release is as of February 15, 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
avelumab, the alliance between Merck KGaA, Darmstadt, Germany, and Pfizer 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 avelumab; 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; 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 in any jurisdictions for potential indications for avelumab,
combination therapies or other product candidates; whether and when
regulatory authorities in any jurisdictions where applications are
pending or may be submitted for avelumab, 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 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, 2016, 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
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