Merck and Pfizer Provide Update on Avelumab in Platinum-Resistant/Refractory Ovarian Cancer

PR76373

DARMSTADT, Germany and NEW YORK, November 19, 2018 /PRNewswire=KYODO JBN/ --

     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(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 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

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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

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company operates as EMD Serono in healthcare, MilliporeSigma in life science,

and EMD Performance Materials.

    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

www.pfizer.com [http://www.pfizer.com ]. In addition, to learn more, please

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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 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 www.sec.gov and www.pfizer.com [http://www.pfizer.com ].

    References

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      . Accessed November 2018.     

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10) Dahan R, Sega E, Engelhardt J, et al. FcgammaRs modulate the anti-tumor

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antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res.

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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. <end_indent>

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