Merck and Pfizer Provide Update on Phase III JAVELIN Lung 200 Trial of Avelumab Monotherapy in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer

PR72334

DARMSTADT, Germany and NEW YORK, February 16, 2018 /PRNewswire=KYODO JBN/ --

     Not intended for UK-based media

    Merck and Pfizer Inc. (NYSE: PFE) today announced results from the Phase

III JAVELIN Lung 200 trial comparing avelumab* to docetaxel in patients with

unresectable, recurrent or metastatic non-small cell lung cancer (NSCLC) whose

disease progressed after treatment with a platinum-containing doublet therapy.

While the trial did not meet its prespecified endpoint of improving overall

survival (OS) in patients with programmed death ligand-1-positive (PD-L1+) (1%

or higher) tumors (HR: 0.90 [96% CI: 0.72-1.12], p-value 0.1627, one-sided),

the proportion of patients in the chemotherapy arm crossing over to immune

checkpoint inhibitors outside the study was higher than previously reported in

post-platinum immunotherapy clinical trials, and this may have confounded this

trial outcome (percentage of patients receiving subsequent checkpoint inhibitor

therapy: docetaxel arm 26.4%; avelumab arm 5.7%).

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    However, improvements in OS versus the control arm were observed in the

moderate-to-high PD-L1+ expression (50% or greater, which represented

approximately 40% of the study population) and high PD-L1+ expression

population (PD-L1+ expression 80% or greater, which represented approximately

30% of the study population) (HR: 0.67 [95% CI: 0.51-0.89], p-value 0.0052,

two-sided; and HR 0.59 [95% CI: 0.42-0.83], p-value 0.0022, two-sided,

respectively*). The safety profile for avelumab in this trial was consistent

with that observed in the overall JAVELIN clinical development program; no new

safety signals were identified.

    "Avelumab performed in line with expectations in the trial from both an

efficacy and safety perspective," said primary investigator Fabrice Barlesi,

M.D., Ph.D., Head of Multidisciplinary Oncology and Therapeutic Innovations

Department at Aix-Marseille University and the Assistance Publique Hopitaux de

Marseille, France. "With immune checkpoint inhibitors approved for patients

with previously treated, advanced non-small cell lung cancer, higher

percentages of immunotherapy-naive patients are receiving subsequent checkpoint

inhibitors in their progressive treatments. This was observed in the JAVELIN

Lung 200 control arm and may have confounded the primary outcome of the study."

    "Avelumab's overall clinical activity in this study supports its profile

with expected efficacy across several endpoints and subgroups," said Luciano

Rossetti, M.D., Executive Vice President, Global Head of Research & Development

at the Biopharma business of Merck. "However, the chemotherapy group displayed

improved overall survival compared with previous PDx trials, most likely due to

the impact of crossover to other checkpoint inhibitors."

    "We are committed to understanding the data in the context of the

subpopulations and the impact of access to other immune checkpoint inhibitors,"

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 will continue to progress the broad avelumab program,

exploring various indications."

    Detailed results from the JAVELIN Lung 200 trial will be submitted for

presentation at an upcoming medical congress, and the companies aim to share

the data with regulatory agencies.

    In 2017, avelumab first received accelerated approval by the US Food and

Drug Administration (FDA) for metastatic Merkel cell carcinoma (mMCC) and for

previously treated patients with locally advanced or metastatic urothelial

carcinoma (mUC), followed by the European Commission (EC) approval for mMCC

later that year.

    The clinical development program for avelumab, known as JAVELIN, involves

at least 30 clinical programs and over 7,000 patients evaluated across more

than 15 different tumor types. In addition to NSCLC, these cancers include

breast, gastric/gastro-esophageal junction, head and neck, Hodgkin's lymphoma,

melanoma, mesothelioma, Merkel cell carcinoma,  ovarian, renal cell carcinoma

and urothelial carcinoma.

    In December 2017, the FDA granted Breakthrough Therapy Designation for

avelumab as a combination therapy for treatment-naive patients with advanced

renal cell carcinoma.

    *Avelumab is under clinical investigation for treatment of NSCLC and has

not been demonstrated to be safe and effective for this indication. There is no

guarantee that avelumab will be approved for NSCLC by any health authority

worldwide.

    *When the primary endpoint is not met, statistical significance cannot be

formally claimed with the predefined statistical significance level (i.e., 0.05

two-sided). In this circumstance, the Type I error is not strictly controlled

and the p-value should be interpreted cautiously.

    About JAVELIN Lung 200

    JAVELIN Lung 200 is a Phase III, randomized, open-label, multicenter trial

investigating avelumab versus docetaxel in patients with locally advanced

unresectable, metastatic or recurrent NSCLC whose disease has progressed after

a platinum-containing doublet chemotherapy. The trial included 792 patients

from approximately 260 sites in North America, South America, Asia, Africa,

Australia and Europe. The primary objective was to demonstrate superior OS

compared with docetaxel in patients with PD-L1+ unresectable, recurrent or

metastatic NSCLC whose disease progressed after treatment with a

platinum-containing doublet therapy.

    About JAVELIN Lung Program

    In addition to JAVELIN Lung 200, avelumab's lung cancer clinical

development program includes several other ongoing clinical trials

investigating avelumab alone and in combination. JAVELIN Lung 100 is a Phase

III randomized open-label, multicenter trial to assess the safety and efficacy

of avelumab, compared with platinum-based doublet chemotherapy, in patients

with metastatic NSCLC who have not previously received any systemic treatment

for their NSCLC. JAVELIN Lung 101 is a Phase Ib/II multicenter, international,

dose-finding trial designed to evaluate the safety and efficacy of avelumab in

combination with either Pfizer's crizotinib or lorlatinib in patients with

advanced or metastatic NSCLC. JAVELIN Medley is a Phase Ib/II randomized

open-label, multicenter dose-finding trial of avelumab in combination with

other immune modulators in patients with selected locally advanced or

metastatic solid tumors, including NSCLC.

    About Non-Small Cell Lung Cancer

    Globally, lung cancer is the most common cause of cancer-related deaths in

men and the second most common in women,1 responsible for more deaths than

colon, breast and prostate cancer combined.2 NSCLC is the most common type of

lung cancer, accounting for 80 to 85% of all lung cancers.3 The five-year

survival rate for people diagnosed with lung cancer that has spread

(metastasized) to other areas of the body is 1%.4

    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.5-7 Avelumab has

also been shown to induce NK cell-mediated direct tumor cell lysis via

antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.7-9 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(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.

    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 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 in 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 EUR 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(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

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    Pfizer Disclosure Notice

    The information contained in this release is as of February 15, 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, 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 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, 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

References  

    1. American Cancer Society (2015) Global facts & figures third edition.

Available from:

http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-044738.pdf

Accessed February 2018.

    2. American Cancer Society (2017) Key statistics for lung cancer. Available

from:

https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html

Accessed February 2018.

    3. American Cancer Society (2016) What is non-small cell lung cancer?

Available from:

https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html

Accessed February 2018.

    4. Cancer.net. Lung cancer - non-small cell: statistics. Available from:

http://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics  

Accessed February 2018.

    5. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of

cancer immunotherapy. Cancer Control 2014;21(3):231-7.

    6. 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):285-95.

    7. 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):1148-57.

    8. Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance

antitumor ADCC. Immunotherapy 2012;4(5):511-27.

    9. Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and

antibody-dependent cytotoxicity. Expert Opin Biol Ther 2017;17(4):515-23.

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SOURCE: Merck KGaA, Darmstadt, Germany