Merck and Pfizer Provide Update on Phase III JAVELIN Lung 200 Trial of Avelumab Monotherapy in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer

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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 EUR 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.

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
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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 U.S. Securities and Exchange Commission and
available at http://www.sec.gov and http://www.pfizer.com.

References

1. 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.
2. 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.
3. 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.
4. Cancer.net. Lung cancer - non-small cell: statistics. Available
from: http://www.cancer.net/cancer-types/lung-cancer-non-small-cel
l/statistics Accessed February 2018.
5. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape
of cancer immunotherapy. Cancer Control 2014;21(3):231-7.
6. Dahan R, Sega E, Engelhardt J, et al. Fc?Rs modulate the
anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis.
Cancer Cell 2015;28(3):285-95.
7. 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.
8. Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to
enhance antitumor ADCC. Immunotherapy 2012;4(5):511-27.
9. 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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