Merck and Pfizer Provide Update on Avelumab inPlatinum-Resistant
Refractory Ovarian Cancer
Darmstadt, Germany and New York (ots/PRNewswire) – Not intended for
US, Canada and UK-based media
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,
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
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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 po
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