DARMSTADT, Germany and NEW YORK, November 28, 2017 /PRNewswire/ --
N ot intended for UK-based media
- Pivotal Phase III J avelin trial investigating avelumab as third-line treatment for patients with
unresectable, recurrent or metastatic gastric cancer did not meet its pre-specified primary endpoint of superior overall
survival compared to chemotherapy
- First global trial of a checkpoint inhibitor versus an active
chemotherapy comparator rather than placebo in this hard-to-treat patient p
opulation
- Safety profile was consistent with that observed in previously reported studies of avelumab ; no new
safety signals were identified
Merck KGaA, Darmstadt, Germany, and Pfizer Inc. (NYSE: PFE) today announced that the Phase
III JAVELIN Gastric 300 trial did not meet its primary endpoint of superior overall survival (OS) with single-agent avelumab*
compared with physician's choice of chemotherapy. The trial investigated avelumab as a third-line treatment for unresectable,
recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma patients whose disease progressed following two
prior therapeutic regimens, regardless of programmed death ligand-1 (PD-L1) expression. The safety profile of avelumab was
consistent with that observed in the overall JAVELIN clinical development program.
"Gastric cancer in the third-line setting is a particularly hard-to-treat and heterogeneous disease, and importantly, this was
the first trial conducted with a checkpoint inhibitor compared to an active chemotherapy comparator rather than placebo in a
global patient population," said Luciano Rossetti, M.D., Executive Vice President, Global Head of
Research & Development at the Biopharma business of Merck KGaA, Darmstadt, Germany, which
operates as EMD Serono in the US and Canada. "Data from this study will provide valuable
information for physicians treating this late stage disease. We remain committed to our ongoing gastric cancer program with
avelumab including the JAVELIN Gastric 100 study in the first-line switch maintenance setting."
"Gastric cancer is a leading cause of cancer death globally with clear unmet needs, and the results provide important insights
as we continue to investigate the role of avelumab for the treatment of gastric cancer," said Chris
Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-Oncology, Early Development and Translational Oncology,
Pfizer Global Product Development. "With approvals for two cancers in 2017, our companies have made tremendous progress with
avelumab on behalf of patients this year, and we are confident that our broad clinical development program in both monotherapy
and combinations across a range of cancers will continue to bring new potential treatment options to patients."
The JAVELIN Gastric 300 data will be further examined in an effort to better understand the results and will also be submitted
for presentation at an upcoming medical congress. The outcome of JAVELIN Gastric 300 does not have any impact on current avelumab
approvals.
JAVELIN Gastric 300 is a Phase III, multicenter, international, randomized, open-label clinical trial investigating avelumab
plus best supportive care versus physician's choice of protocol-specified chemotherapy (paclitaxel or irinotecan monotherapy)
plus best supportive care in patients with unresectable, recurrent or metastatic gastric or GEJ adenocarcinoma whose disease has
progressed following two prior therapeutic regimens. The trial enrolled 371 patients from 147 sites in Asia, Australia, Europe, North America and South America. The primary endpoint was OS.
The avelumab gastric clinical development program also includes JAVELIN Gastric 100, a multicenter, randomized, open-label
Phase III study evaluating avelumab as first-line maintenance therapy following induction chemotherapy in unresectable, locally
advanced or metastatic gastric or GEJ cancer. The trial will continue as planned.
*Avelumab is under clinical investigation for treatment of gastric/GEJ cancer and has not been demonstrated to be safe and
effective for this indication. There is no guarantee that avelumab will be approved for gastric/GEJ cancer by any health
authority worldwide.
About Gastric/Gastroe sophageal Junction Cancer
Globally, gastric cancer is the fifth most common cancer but the third most common cause of cancer death.[
1 ] , [ 2 ] In 2012, there were approximately 950,000 new cases
and 723,000 deaths worldwide.[ 3 ] Of these cancers, 90 to 95 percent were
adenocarcinomas.[ 4 ] Incidence varies by country, with higher rates seen in
Central/Eastern Europe, Eastern Asia and South America.[ 5 ] Survival in advanced disease is poor and generally less
than one year.[ 6 ] Globally, there is no recommended therapeutic approach for patients who
progress after two lines of therapy for recurrent or metastatic gastric cancer.
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.[ 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 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 (MCC) and (ii) patients with locally advanced or metastatic urothelial
carcinoma (UC) 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.
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
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About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, is a leading science and technology company in healthcare, life
science and performance materials. Around 50,000 employees work to further develop technologies that improve and enhance life -
from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and
production, to liquid crystals for smartphones and LCD televisions. In 2016, Merck KGaA, Darmstadt, Germany, generated sales of € 15.0 billion in 66 countries.
Founded in 1668, Merck KGaA, Darmstadt, Germany, is the world's oldest pharmaceutical
and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck KGaA,
Darmstadt, Germany, holds the global rights to the "Merck" name and brand except in the United States and Canada, where the company operates as EMD Serono,
MilliporeSigma 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 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 28, 2017. 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 BAVENCIO (avelumab), 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 BAVENCIO; 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 and when any other drug applications may
be filed in any jurisdictions for potential indications for BAVENCIO, combination therapies or other product candidates; whether
and when regulatory authorities in any other jurisdictions where applications are pending or may be submitted for BAVENCIO,
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 BAVENCIO, 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, 2016, 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
- Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D,
Bray, F. GLOBOCAN 2012 v1.1, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2014. Available at: http://globocan.iarc.fr. Accessed: November 2017.
- International Agency for Research on Cancer. GLOBOCAN 2012 Available at: http://globocan.iarc.fr/old/FactSheets/cancers/stomach-new.asp. Accessed: November
2017.
- Chapter 1, Cancer Worldwide. In: Stewart BW, Wild CP (eds). World Cancer Report 2014: International Agency for Research on
Cancer, World Health Organization; 2014.
- Waddell T et al. Ann O ncol 2013;24(Suppl 6):vi57-63.
- International Agency for Research on Cancer. WHO. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality, and Prevalence
Worldwide in 2012 2012 [06 April 2015]. Available from: http://globocan.iarc.fr/Default.aspx. Accessed: November 2017.
- Shah MA. J Clin Oncol 2015;33:1760-9.
- Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control.
2014;21(3):231-237.
- Dahan R, Sega E, Engelhardt J, Selby M, Korman AJ, Ravetch JV. FcγRs modulate the anti-tumor activity of antibodies
targeting the PD-1/PD-L1 axis.Cancer Cell. 2015;28(3):285-295.
- 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.
- Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance antitumor ADCC. Immunotherapy.
2012;4(5):511-527.
- 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)
Sally Beatty
+1-212-733-6566
Investor Relations
Ryan Crowe
+1-212-733-8160
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SOURCE Merck KGaA, Darmstadt, Germany