Merck and Pfizer Provide Update on JAVELIN Ovarian 100 Trial of Avelumab in Previously Untreated Advanced Ovarian Cancer
Merck and Pfizer Provide Update on JAVELIN Ovarian 100 Trial of Avelumab in Previously Untreated Advanced Ovarian Cancer
PR76888
DARMSTADT, Germany and NEW YORK, Dec. 22, 2018 /PRNewswire=KYODO JBN/--
Not intended for US, Canada and UK-based media
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(R))
Avelumab (BAVENCIO(R)) 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(R))
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(R) 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
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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(R)
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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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:
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.wcrf.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. FcgammaRs 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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