DARMSTADT, Germany and
NEW YORK, February 15, 2018 /PRNewswire/ --
Not intended for UK-based media
Merck 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%).
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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. "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 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
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 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 avelumab, an
anti-PD-L1 antibody initially discovered and developed by Merck.
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 in combination regimens, and is striving to find new ways to
treat cancer.
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About Merck
Merck 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 generated sales of € 15.0 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.
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At Pfizer, we apply science and our global resources to bring
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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 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 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
subsequent reports on Form 8-K, all of which are filed with the
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References
- American Cancer Society (2015) Global facts & figures third
edition. Available from:
http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-044738.pdf
Accessed February 2018.
- American Cancer Society (2017) Key statistics for lung cancer.
Available from:
https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html
Accessed February 2018.
- American Cancer Society (2016) What is non-small cell lung
cancer? Available from:
https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html
Accessed February 2018.
- Cancer.net. Lung cancer - non-small cell: statistics. Available
from:
http://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics
Accessed February 2018.
- Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the
landscape of cancer immunotherapy. Cancer Control
2014;21(3):231-7.
- 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):285-95.
- 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):1148-57.
- Kohrt HE, Houot R, Marabelle A, et al. Combination strategies
to enhance antitumor ADCC. Immunotherapy
2012;4(5):511-27.
- Hamilton G, Rath B. Avelumab: combining immune checkpoint
inhibition and antibody-dependent cytotoxicity. Expert Opin
Biol Ther 2017;17(4):515-23.
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