Merck and Pfizer Provide Update on Avelumab in Platinum-Resistant/Refractory Ovarian Cancer

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

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Merck and Pfizer Inc. (NYSE: PFE) today announced that the Phase
III JAVELIN Ovarian 200 trial evaluating avelumab* alone or in
combination with pegylated liposomal doxorubicin (PLD), a type of
chemotherapy, compared with PLD did not meet the prespecified primary
endpoints of overall survival (OS) or progression-free survival (PFS)
in patients with platinum-resistant or -refractory ovarian cancer.
Signals were observed in the combination arm relative to PLD, and
further analyses of the trial are warranted (HR for the primary PFS
endpoint for avelumab + PLD vs PLD alone: 0.78 [repeated confidence
interval (RCI): 0.587, 1.244; one-sided p-value: 0.0301]; HR for the
primary OS endpoint for avelumab + PLD vs PLD alone: 0.89 [RCI:
0.744, 1.241; one-sided p-value: 0.2082]; HR for the primary PFS
endpoint for avelumab alone vs PLD alone: 1.68 [RCI: 1.320, 2.601;
one-sided p-value: >0.99]; HR for the primary OS endpoint for
avelumab alone vs PLD alone: 1.14 [RCI: 0.948, 1.580; one-sided
p-value: 0.8253]; objective response, a secondary endpoint: 13.3%
[95% CI 8.8, 19.0] for avelumab + PLD; 3.7% [95% CI 1.5, 7.5] for
avelumab alone; and 4.2% [95% CI 1.8, 8.1] for PLD alone). No new
safety signals were observed for avelumab alone or in combination,
and the safety profile for avelumab in this trial was consistent with
that observed in the overall JAVELIN clinical development program.
The data are currently being analyzed, and detailed results will be
shared with the scientific community.

"JAVELIN Ovarian 200 enrolled a high proportion of patients with
aggressive, refractory disease that had no response to prior
platinum-based chemotherapy, a population known to have disease that
is challenging to treat; as such, this group of patients is typically
not included in Phase III ovarian cancer trials," 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 initiated the JAVELIN Ovarian 200 trial as the first
Phase III study of a checkpoint inhibitor in the platinum-resistant
or -refractory setting recognizing these patients have the most
pressing need for new treatment options. The results speak to the
significant challenges these women face."

"Although OS and PFS did not reach statistical significance, study
results indicate potential clinical activity of the combination of
avelumab and chemotherapy which will be analyzed further," said
Luciano Rossetti, M.D., Executive Vice President, Global Head of
Research & Development at the Biopharma business of Merck. "We thank
the patients, their families and the investigators who participated
in the JAVELIN Ovarian 200 trial, and wish to underscore that the
alliance remains committed to driving advances in ovarian cancer, a
commitment that includes two ongoing Phase III trials in previously
untreated patients testing avelumab in combination with chemotherapy
and, separately, one in combination with chemotherapy followed by
maintenance treatment of avelumab in combination with a PARP
inhibitor."

"Effective management of platinum-resistant or -refractory ovarian
cancer remains the biggest unmet medical need facing women with
recurrent ovarian cancer today. The current treatment options have
only limited and short-lived efficacy for the majority of women, as
evidenced by an average life expectancy that does not exceed one year
for this group," said Eric Pujade-Lauraine, M.D., Ph.D., head of the
Women Cancers and Clinical Research Department at Hôpitaux
Universitaires Paris Centre, site Hôtel-Dieu. "As a researcher and
clinician, I know how important it is to continue to improve the
outlook for women with advanced ovarian cancer and look forward to
the results of more trials exploring the role of avelumab in delaying
recurrence in platinum-sensitive patients and earlier lines of
therapy."

Four out of five patients with ovarian cancer are diagnosed at
advanced stages. The disease often has no symptoms early on, when it
is much more treatable.1 Approximately 70% of patients with ovarian
cancer who receive standard-of-care, frontline, platinum-based
chemotherapy will relapse in the first three years.2 At first
relapse, approximately 20% to 25% of ovarian cancer patients have
platinum-resistant or -refractory disease, and eventually almost all
patients will become platinum-resistant.3-6

JAVELIN Ovarian 200 is a Phase III, multicenter, randomized study
investigating the efficacy and safety of avelumab alone or in
combination with PLD versus PLD alone in 566 women with ovarian
cancer that is resistant or refractory to platinum chemotherapy. The
primary objectives were to demonstrate superior OS or PFS for one or
both avelumab-based treatment regimens compared with PLD.

In addition to JAVELIN Ovarian 200, the avelumab ovarian cancer
clinical development program includes several ongoing clinical trials
investigating avelumab in combination with other therapies. JAVELIN
Ovarian 100 is an open-label, international, multicenter, randomized
Phase III study of avelumab in combination with and/or as follow-on
(maintenance) treatment to platinum-based chemotherapy in previously
untreated patients with locally advanced or metastatic (Stage III or
Stage IV) epithelial ovarian cancer. JAVELIN Ovarian 100 is the first
Phase III study to evaluate the addition of an immunotherapy to the
standard of care in frontline treatment for this aggressive disease.
JAVELIN Ovarian PARP 100 is a randomized, open-label, multicenter
Phase III study of avelumab plus chemotherapy followed by maintenance
therapy of avelumab in combination with a PARP inhibitor or
chemotherapy followed by maintenance therapy with a PARP inhibitor,
in patients with previously untreated advanced ovarian cancer.
Avelumab is also undergoing investigation in combination with other
therapies for gynecologic cancers.

*Avelumab is under clinical investigation for treatment of ovarian
cancer and has not been demonstrated to be safe and effective for
this indication. There is no guarantee that avelumab will be approved
for ovarian cancer by any health authority worldwide.

About the JAVELIN Clinical Trial 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,
melanoma, mesothelioma, 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.7 The disease is generally advanced when it is
diagnosed, as it often has few to no symptoms at the early stages.
This makes it difficult to detect until the disease has progressed.
Symptoms 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%.7,8

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.9-11 Avelumab has also been shown to
induce NK cell-mediated direct tumor cell lysis via
antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.11-13
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
35 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, the vibrant science and technology company, operates across
healthcare, life science and performance materials. Almost 53,000
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 company
operates as EMD Serono in healthcare, MilliporeSigma in life science,
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,
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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
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Pfizer Disclosure Notice

The information contained in this release is as of November 19,
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 www.sec.gov and www.pfizer.com.

References

1. American Cancer Society. Facts and figures 2018. Special section:
ovarian cancer. Available at: https://www.cancer.org/content/dam/
cancer-org/research/cancer-facts-and-statistics/annual-cancer-fac
ts-and-figures/2018/cancer-facts-and-figures-special-section-ovar
ian-cancer-2018.pdf. Accessed November 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. Christie EL, Bowtell DD. Acquired chemotherapy resistance in
ovarian cancer. Ann Oncol. 2017; 28 (Supplement 8):viii13-viii15.
4. Cooke SL, Brenton JD. Evolution of platinum resistance in
high-grade serous ovarian cancer. Lancet Oncol. 2011;
12(12):1169-1174.
5. Tomao F, Marchetti C, Romito A, et al. Overcoming platinum
resistance in ovarian cancer treatment: from clinical practice to
emerging chemical therapies. Expert Opin Pharmacother.
2017;18(14):1443-1455.
6. Committee on the State of the Science in Ovarian Cancer Research;
Board on Health Care Services; Institute of Medicine; National
Academies of Sciences, Engineering, and Medicine. Washington
(DC): National Academies Press (US); 2016 Apr 25.
7. 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 November 2018.
8. 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
November 2018
9. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the
landscape of cancer immunotherapy. Cancer Control.
2014;21(3):231-237.
10. 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.
11. 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.
12. Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to
enhance antitumor ADCC. Immunotherapy. 2012;4(5):511-527.
13. Hamilton G, Rath B. Avelumab: combining immune checkpoint
inhibition and antibody-dependent cytotoxicity. Expert Opin Biol
Ther. 2017;17(4):515-523.

Contacts

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+1-212-733-8160

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