DARMSTADT, Germany and
NEW YORK, November 19, 2018 /PRNewswire/ --
Not intended for UK-based media
Merck KGaA, Darmstadt, Germany,
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 KGaA, Darmstadt,
Germany, which in the US and
Canada operates as EMD Serono. "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 KGaA, Darmstadt, Germany, 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.
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
BAVENCIO can cause immune-mediated pneumonitis, including
fatal cases. Monitor patients for signs and symptoms of
pneumonitis, and evaluate suspected cases with radiographic
imaging. Administer corticosteroids for Grade 2 or greater
pneumonitis. Withhold BAVENCIO for moderate (Grade 2) and
permanently discontinue for severe (Grade 3), life-threatening
(Grade 4), or recurrent moderate (Grade 2) pneumonitis. Pneumonitis
occurred in 1.2% (21/1738) of patients, including one (0.1%)
patient with Grade 5, one (0.1%) with Grade 4, and five (0.3%) with
Grade 3.
BAVENCIO can cause immune-mediated hepatitis, including
fatal cases. Monitor patients for abnormal liver tests prior to and
periodically during treatment. Administer corticosteroids for Grade
2 or greater hepatitis. Withhold BAVENCIO for moderate (Grade 2)
immune-mediated hepatitis until resolution and permanently
discontinue for severe (Grade 3) or life-threatening (Grade 4)
immune-mediated hepatitis. Immune-mediated hepatitis was reported
in 0.9% (16/1738) of patients, including two (0.1%) patients with
Grade 5, and 11 (0.6%) with Grade 3.
BAVENCIO can cause immune-mediated colitis. Monitor
patients for signs and symptoms of colitis. Administer
corticosteroids for Grade 2 or greater colitis. Withhold BAVENCIO
until resolution for moderate or severe (Grade 2 or 3) colitis, and
permanently discontinue for life-threatening (Grade 4) or recurrent
(Grade 3) colitis upon reinitiation of BAVENCIO. Immune-mediated
colitis occurred in 1.5% (26/1738) of patients, including seven
(0.4%) with Grade 3.
BAVENCIO can cause immune-mediated endocrinopathies,
including adrenal insufficiency, thyroid disorders, and type 1
diabetes mellitus.
Monitor patients for signs and symptoms of adrenal
insufficiency during and after treatment, and administer
corticosteroids as appropriate. Withhold BAVENCIO for severe (Grade
3) or life-threatening (Grade 4) adrenal insufficiency. Adrenal
insufficiency was reported in 0.5% (8/1738) of patients, including
one (0.1%) with Grade 3.
Thyroid disorders can occur at any time during treatment.
Monitor patients for changes in thyroid function at the start of
treatment, periodically during treatment, and as indicated based on
clinical evaluation. Manage hypothyroidism with hormone replacement
therapy and hyperthyroidism with medical management. Withhold
BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) thyroid
disorders. Thyroid disorders, including hypothyroidism,
hyperthyroidism, and thyroiditis, were reported in 6% (98/1738) of
patients, including three (0.2%) with Grade 3.
Type 1 diabetes mellitus including diabetic ketoacidosis:
Monitor patients for hyperglycemia or other signs and symptoms of
diabetes. Withhold BAVENCIO and administer antihyperglycemics or
insulin in patients with severe or life-threatening (Grade ≥ 3)
hyperglycemia, and resume treatment when metabolic control is
achieved. Type 1 diabetes mellitus without an alternative etiology
occurred in 0.1% (2/1738) of patients, including two cases of Grade
3 hyperglycemia.
BAVENCIO can cause immune-mediated nephritis and renal
dysfunction. Monitor patients for elevated serum creatinine
prior to and periodically during treatment. Administer
corticosteroids for Grade 2 or greater nephritis. Withhold BAVENCIO
for moderate (Grade 2) or severe (Grade 3) nephritis until
resolution to Grade 1 or lower. Permanently discontinue BAVENCIO
for life-threatening (Grade 4) nephritis. Immune-mediated nephritis
occurred in 0.1% (1/1738) of patients.
BAVENCIO can result in other severe and fatal immune-mediated
adverse reactions involving any organ system during treatment
or after treatment discontinuation. For suspected immune-mediated
adverse reactions, evaluate to confirm or rule out an
immune-mediated adverse reaction and to exclude other causes.
Depending on the severity of the adverse reaction, withhold or
permanently discontinue BAVENCIO, administer high-dose
corticosteroids, and initiate hormone replacement therapy, if
appropriate. Resume BAVENCIO when the immune-mediated adverse
reaction remains at Grade 1 or lower following a corticosteroid
taper. Permanently discontinue BAVENCIO for any severe (Grade 3)
immune-mediated adverse reaction that recurs and for any
life-threatening (Grade 4) immune-mediated adverse reaction. The
following clinically significant immune-mediated adverse reactions
occurred in less than 1% of 1738 patients treated with BAVENCIO:
myocarditis with fatal cases, myositis, psoriasis, arthritis,
exfoliative dermatitis, erythema multiforme, pemphigoid,
hypopituitarism, uveitis, Guillain-Barré syndrome, and systemic
inflammatory response.
BAVENCIO can cause severe (Grade 3) or life-threatening (Grade
4) infusion-related reactions. Patients should be
premedicated with an antihistamine and acetaminophen prior to the
first 4 infusions and for subsequent doses based upon clinical
judgment and presence/severity of prior infusion reactions. Monitor
patients for signs and symptoms of infusion-related reactions,
including pyrexia, chills, flushing, hypotension, dyspnea,
wheezing, back pain, abdominal pain, and urticaria. Interrupt or
slow the rate of infusion for mild (Grade 1) or moderate (Grade 2)
infusion-related reactions. Permanently discontinue BAVENCIO for
severe (Grade 3) or life-threatening (Grade 4) infusion-related
reactions. Infusion-related reactions occurred in 25% (439/1738) of
patients, including three (0.2%) patients with Grade 4 and nine
(0.5%) with Grade 3.
BAVENCIO can cause fetal harm when administered to a
pregnant woman. Advise patients of the potential risk to a fetus
including the risk of fetal death. Advise females of childbearing
potential to use effective contraception during treatment with
BAVENCIO and for at least 1 month after the last dose of BAVENCIO.
It is not known whether BAVENCIO is excreted in human milk. Advise
a lactating woman not to breastfeed during treatment and for
at least 1 month after the last dose of BAVENCIO due to the
potential for serious adverse reactions in breastfed infants.
The most common adverse reactions (all grades, ≥ 20%) in
patients with metastatic Merkel cell carcinoma (MCC) were
fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea
(22%), infusion-related reaction (22%), rash (22%), decreased
appetite (20%), and peripheral edema (20%).
Selected treatment-emergent laboratory abnormalities (all
grades, ≥ 20%) in patients with metastatic MCC were
lymphopenia (49%), anemia (35%), increased aspartate
aminotransferase (34%), thrombocytopenia (27%), and increased
alanine aminotransferase (20%).
The most common adverse reactions (all grades, ≥ 20%) in
patients with locally advanced or metastatic urothelial
carcinoma (UC) were fatigue (41%), infusion-related
reaction (30%), musculoskeletal pain (25%), nausea (24%), decreased
appetite/hypophagia (21%), and urinary tract infection (21%).
Selected laboratory abnormalities (Grades 3-4, ≥ 3%) in
patients with locally advanced or metastatic UC were
hyponatremia (16%), increased gamma-glutamyltransferase (12%),
lymphopenia (11%), hyperglycemia (9%), increased alkaline
phosphatase (7%), anemia (6%), increased lipase (6%), hyperkalemia
(3%), and increased aspartate aminotransferase (3%).
Please see full US Prescribing Information and Medication Guide
available at http://www.BAVENCIO.com.
Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US
Immuno-oncology is a top priority for Merck KGaA, Darmstadt,
Germany, and Pfizer. The global
strategic alliance between Merck KGaA, Darmstadt, Germany, 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 KGaA,
Darmstadt, Germany. 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.
All Merck KGaA, Darmstadt, Germany, Press Releases are distributed by
e-mail at the same time they become available on the Merck KGaA,
Darmstadt, Germany, Website.
Please go to http://www.emdgroup.com/subscribe to register online,
change your selection or discontinue this service.
About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany,
the vibrant science and technology company, operates across
healthcare, life science and performance materials. Around 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 - the company is everywhere.
In 2017, Merck KGaA, Darmstadt, Germany, generated sales of € 15.3 billion in
66 countries.
The company holds the global rights to the name and trademark
"Merck" internationally. The only exceptions are the United States and Canada, where the company's businesss sectors
operate as EMD Serono in healthcare, MilliporeSigma in life
science, and EMD Performance Materials. Since its founding 1666,
scientific exploration and responsible entrepreneurship have been
key to the company's technological and scientific advances. To this
day, the founding family remains the majority owner of the publicly
listed company.
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 http://www.pfizer.com. In addition, to learn more, please
visit us on http://www.pfizer.com and follow us on
Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us
on Facebook at Facebook.com/Pfizer.
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 alliance between Merck KGaA,
Darmstadt, Germany, and Pfizer
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 for avelumab in any
jurisdictions or 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. 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-facts-and-figures/2018/cancer-facts-and-figures-special-section-ovarian-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.wcrf.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. FcγRs 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
Merck KGaA, Darmstadt, Germany
Media
Friederike Segeberg
+49-6151-72-6328
Investor Relations
+49-6151-72-3321
Pfizer
Media (US)
Jessica Smith
+1-212-733-6213
Investor Relations
Ryan Crowe
+1-212-733-8160
(Logo:
http://mma.prnewswire.com/media/611455/Merck_KGaA_Pfizer_Logo.jpg
)
SOURCE Merck