Merck and Pfizer Provide Update on JAVELIN Ovarian 100 Trial of Avelumab in Previously Untreated Advanced Ovarian Cancer

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

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Merck and Pfizer Inc. (NYSE: PFE) today announced that data from a
planned interim analysis of the Phase III JAVELIN Ovarian 100 study
of avelumab* did not support the study's initial hypothesis, and
therefore the alliance made the decision to terminate the trial in
alignment with the independent Data Monitoring Committee.

The Merck-Pfizer alliance was the first to test an immunotherapy
in this indication, given the significant unmet need in the treatment
of ovarian cancer. Four out of five women with ovarian cancer are
diagnosed at advanced stages.[1] Most women with advanced ovarian
cancer ultimately die within five years due to refractory, resistant
or recurrent disease.[2],[3]

Topline results showed that the study, which is evaluating
avelumab in combination with and/or following platinum-based
chemotherapy in previously untreated patients with ovarian cancer,
would not achieve superiority in the pre-specified primary endpoint
of progression-free survival. While detailed analyses of the data are
ongoing, no new safety signals were observed, and the safety profile
for avelumab in this trial appears consistent with that observed in
the overall JAVELIN clinical development program. The alliance has
notified health authorities and trial investigators of the interim
findings and the decision to discontinue the trial. Detailed results
will be shared with the scientific community. The JAVELIN Ovarian
PARP 100 study and earlier phase studies investigating avelumab in
various combinations are ongoing.

*Avelumab is under clinical investigation for treatment of ovarian
cancer. There is no guarantee that avelumab will be approved for
ovarian cancer by any health authority worldwide.

About JAVELIN Ovarian 100

JAVELIN Ovarian 100 is a Phase III, multicenter, randomized,
three-arm study investigating avelumab in combination with and/or as
a maintenance treatment following carboplatin/paclitaxel chemotherapy
in 998 previously untreated patients with locally advanced or
metastatic (Stage III or Stage IV) epithelial ovarian cancer,
fallopian tube cancer (FTC), or primary peritoneal cancer. The three
arms are carboplatin/paclitaxel followed by observation;
carboplatin/paclitaxel followed by avelumab maintenance; and avelumab
plus carboplatin/paclitaxel followed by avelumab maintenance. The
primary objectives are to demonstrate superior PFS for one or both
avelumab-based treatment regimens compared with
carboplatin/paclitaxel followed by observation.

About the JAVELIN Clinical Development Program

The clinical development program for avelumab, known as JAVELIN,
involves at least 30 clinical programs and more than 9,000 patients
evaluated across more than 15 different tumor types. In addition to
ovarian cancer, these tumor types include breast,
gastric/gastro-esophageal junction and head and neck cancers, Merkel
cell carcinoma, non-small cell lung cancer, renal cell carcinoma and
urothelial carcinoma.

About Ovarian Cancer

Every year, more than 295,000 women are diagnosed with ovarian
cancer worldwide.[4] The disease is generally advanced when it is
diagnosed, as it often has few to no symptoms at the early stages,
making it difficult to detect. Symptoms also can be vague or
non-specific, making it easy to confuse with less serious
non-cancerous conditions. The five-year survival rate ranges from
approximately 30% to 50%, but for those with metastatic disease, it
drops to less than 20%.[5],[6]

About Avelumab (BAVENCIO®)

Avelumab (BAVENCIO®) 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.[7]-[9] Avelumab has also been shown
to induce NK cell-mediated direct tumor cell lysis via
antibody-dependent cell-mediated cytotoxicity (ADCC) in
vitro.[9]-[11] In November 2014, Merck and Pfizer announced a
strategic alliance to co-develop and co-commercialize avelumab.

Approved Indications in the US

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.

Avelumab is currently approved for patients with MCC in more than
45 countries globally, with the majority of these approvals in a
broad indication that is not limited to a specific line of treatment.

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 avelumab 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 combination
regimens, and is striving to find new ways to treat cancer.

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About Merck

Merck, a vibrant science and technology company, operates across
healthcare, life science and performance materials. Around 51,000
employees work to make a positive difference to millions of people's
lives every day by creating more joyful and sustainable ways to live.
From advancing gene editing technologies and discovering unique ways
to treat the most challenging diseases to enabling the intelligence
of devices - Merck is everywhere. In 2017, Merck generated sales of
EUR 15.3 billion in 66 countries.

Scientific exploration and responsible entrepreneurship have been
key to Merck's technological and scientific advances. This is how
Merck has thrived since its founding in 1668. The founding family
remains the majority owner of the publicly listed company. Merck
holds the global rights to the Merck name and brand. The only
exceptions are the United States and Canada, where the business
sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma
in life science, and EMD Performance Materials. For more information
about Merck visit http://www.merckgroup.com.

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
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Facebook.com/Pfizer.

Pfizer Disclosure Notice

The information contained in this release is as of December 21,
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,
including clinical trials evaluating avelumab for the treatment of
ovarian cancer, 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 any 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, 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. American Cancer Society. Survival Rates for Ovarian Cancer, by
Stage. Available at: https://www.cancer.org/content/dam/cancer-or
g/research/cancer-facts-and-statistics/annual-cancer-facts-and-fi
gures/2018/cancer-facts-and-figures-special-section-ovarian-cance
r-2018.pdf. Accessed December 2018.
2. Ledermann, JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and
relapsed epithelial ovarian carcinoma: ESMO Clinical Practice
Guidelines for diagnosis, treatment and follow-up. Ann Oncol.
2013; 24 (Supplement 6): vi24-vi32, doi:10.1093/annonc/mdt333.
3. Ozol, RJ. Challenges for chemotherapy in ovarian cancer. Annals
of Oncology 2006;17(5):v181-187.
4. World Cancer Research Fund / American Institute for Cancer
Research. Continuous Update Project. Available at: https://www.wc
rf.org/dietandcancer/cancer-trends/worldwide-cancer-data.
Accessed December 2018.
5. World Cancer Research Fund / American Institute for Cancer
Research. Continuous Update Project. Available at:
https://www.wcrf.org/dietandcancer/ovarian-cancer. Accessed
December 2018.
6. American Cancer Society. Survival Rates for Ovarian Cancer, by
Stage. Available at: https://www.cancer.org/cancer/ovarian-cancer
/detection-diagnosis-staging/survival-rates.html. Accessed
December 2018.
7. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the
landscape of cancer immunotherapy. Cancer Control.
2014;21(3):231-237.
8. 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):285-295.
9. 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.
10. Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to
enhance antitumor ADCC. Immunotherapy. 2012;4(5):511-527.
11. Hamilton G, Rath B. Avelumab: combining immune checkpoint
inhibition and antibody-dependent cytotoxicity. Expert Opin Biol
Ther. 2017;17(4):515-523.

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