Merck and Pfizer Provide Update on Phase III JAVELIN Gastric 300 Study in Patients With Pre-Treated Advanced Gastric Cancer

PR71279

DARMSTADT, Germany and NEW YORK, Nov. 29, /PRNewswire=KYODO JBN/--

Not intended for UK-based media

- Pivotal Phase III Javelin 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 population   

Safety profile was consistent with that observed in previously reported studies

of avelumab; no new safety signals were identified   

- Merck 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. "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/Gastroesophageal 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 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

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 BAVENCIO for mMCC and patients with locally advanced or metastatic

UC 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 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 generated sales of € 15.0 billion in 66 countries.

Founded in 1668, Merck is the world's oldest pharmaceutical and chemical

company. The founding family remains the majority owner of the publicly listed

corporate group. Merck, 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

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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

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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 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 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;

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Waddell T et al. Ann Oncol 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.

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Dahan R, Sega E, Engelhardt J, Selby M, Korman AJ, Ravetch JV. FcãRs 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  

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