Shaping Cancer Care Today and Tomorrow: Merck, KGaA, Darmstadt, Germany, to Present New Data from Rapidly Evolving Pipeline at ASCO 2017

In addition to avelumab data, Merck, KGaA, Darmstadt, Germany, will also feature new research at ASCO on its investigational bifunctional immunotherapy anti-PD-L1/TGF-ß trap (M7824), which is thought to simultaneously block both PD-L1 and TGF-ß. An oral presentation will showcase dose escalation Phase I clinical data exploring the potential of M7824 in advanced solid tumors.

Pipeline updates at ASCO also include early clinical results for both Tepotinib, an investigational small-molecule inhibitor of the c-Met receptor tyrosine kinase, M7583, an oral, highly selective, covalent inhibitor of Bruton's tyrosine kinase (BTK), and the first clinical data for M3814, an investigational DNA-dependent protein kinase (DNA-PK) inhibitor. Merck, KGaA, Darmstadt, Germany, is investing significant resources in the promising area of DDR to be a leader in this field. Merck, KGaA, Darmstadt, Germany, has recently in-licensed two promising clinical-stage programs from Vertex.

This highly focused approach to research and development channels Merck, KGaA, Darmstadt, Germany's scientific expertise in areas of high unmet need, a legacy started with Erbitux. Multiple presentations at ASCO reinforce Erbitux as a standard-of-care treatment in squamous cell carcinoma of the head and neck (SCCHN) and metastatic colorectal cancer (mCRC), providing valuable information about biomarkers, disease response, and the importance of tumor location in mCRC, to best target treatment to the right patients.

*Avelumab is under clinical investigation for treatment of NSCLC, RCC, DLBCL, SSCHN and mCRPC and has not been demonstrated to be safe and effective for these indications. There is no guarantee that avelumab will be approved for NSCLC, RCC, DLBCL, SSCHN and mCRPC by any health authority worldwide.

**Tepotinib is the proposed nonproprietary name for the c-Met kinase inhibitor (also known as MSC2156119J).

Tepotinib, M7824 and M3814 are under clinical investigation and have not been proven to be safe and effective. There is no guarantee any product will be approved in the sought-after indication by any health authority worldwide.

Notes to Editors 

Accepted Merck, KGaA, Darmstadt, Germany-supported key abstracts slated for presentation are listed below. In addition, a number of investigator-sponsored studies have been accepted, including multiple abstracts related to Erbitux and avelumab (not listed).

   
                                              Presentation
                                              Date / Time
    Title              Lead Author Abstract # (CDT)           Location
    M7824 (TGF-ss trap)
    Oral Presentation
    Solid Tumors

    Preliminary
    results from a
    phase 1 trial of
    M7824
    (MSB0011359C), a
    bifunctional
    fusion protein                            June 5
    targeting PD-L1
    and TGF-beta, in
    advanced solid
    tumors             JL Gulley   3006       13:15-16:27     Hall D1

   
                                                 Presentation
                                                 Date / Time
    Title              Lead Author   Abstract #  (CDT)           Location
    Avelumab
    Oral Presentation
    Renal Cell
    Carcinoma

    (JAVELIN Renal
    100)

    First-line
    avelumab +
    axitinib therapy
    in patients with                             June 5
    advanced renal
    cell carcinoma:
    results from a                                               Arie Crown
    phase 1b trial     TK Choueiri   4504        8:00-11:00      Theater     Poster Sessions
    Non-Small Cell
    Lung Cancer
    (JAVELIN Solid
    Tumor)

    Exposure-response
    and PD-L1
    expression
    analysis of
    second-line
    avelumab in
    patients with                    9086        June 3
    advanced NSCLC:
    Data from the
    JAVELIN Solid
    Tumor trial        JL Gulley                 8:00-11:30      Hall A

    Merkel Cell
    Carcinoma (JAVELIN
    Merkel 200)

    First-line
    avelumab treatment
    in patients with
    metastatic Merkel                9530        June 3
    cell carcinoma:
    preliminary data
    from an ongoing
    study              S D'Angelo                13:15-16:45     Hall A

    Merkel Cell
    Carcinoma (JAVELIN
    Merkel 200)

    Exploratory
    biomarker analysis
    in patients with
    chemotherapy-refra               9557        June 3
    ctory metastatic
    Merkel cell
    carcinoma treated
    with avelumab      I Shapiro                 13:15-16:45     Hall A

    Urothelial
    Carcinoma

    Updated efficacy
    and safety of
    avelumab in
    metastatic
    urothelial
    carcinoma: pooled                4528        June 4
    analysis from 2
    cohorts of the
    phase 1b JAVELIN
    Solid Tumor study  AB Apolo                  8:00-11:30      Hall A

    Renal Cell
    Carcinoma (JAVELIN
    Renal 101)

    Avelumab plus
    axitinib vs
    sunitinib as
    first-line
    treatment of
    advanced renal                               June 4
    cell carcinoma:
    phase 3 study
    (JAVELIN Renal
    101)               TK Choueiri   TPS4594     8:00-11:30      Hall A

    Pan-Tumor

    (JAVELIN Solid
    Tumor)

    Safety profile of
    avelumab in
    patients with                    3059        June 5
    advanced solid
    tumors: a JAVELIN
    pooled analysis of
    phase 1 and 2 data K Kelly                   8:00-11:30      Hall A

    Lymphoma (TiP)

    (JAVELIN DLBCL)

    Phase 1b/3 study
    of avelumab-based
    combination
    regimens in
    patients (pts)
    with relapsed or                             June 5
    refractory diffuse
    large B-cell
    lymphoma (R/R
    DLBCL)             R Chen        TPS7575     8:00-11:30      Hall A

    Prostate Cancer

    (JAVELIN Solid
    Tumor)

    Avelumab in                      5037        June 5
    metastatic
    castration-resistant
    prostate cancer   
    (mCRPC)            F Fakhrejahani            13:15-16:45     Hall A

    Head and Neck
    Cancer (TiP)

    (JAVELIN Head and
    Neck 100)

    JAVELIN Head and
    Neck 100: a phase
    3 trial of
    avelumab in
    combination with
    chemoradiotherapy
    (CRT) vs CRT for
    1st-line treatment
    of locally                                   June 5
    advanced squamous
    cell carcinoma of
    the head and neck
    (LA SCCHN)         NY Lee        TPS6093     13:15-16:45     Hall A

    Publications
    Merkel Cell
    Carcinoma (JAVELIN
    Merkel 200)

    Non-progression
    during avelumab
    treatment is
    associated with
    clinically
    relevant
    improvements in
    health-related
    quality of life in
    patients with
    Merkel cell
    carcinoma          M Bharmal     e21070      N/A             N/A

    Merkel Cell
    Carcinoma (JAVELIN
    Merkel 200)

    Patient
    experiences with
    avelumab vs
    chemotherapy for
    treating Merkel
    cell carcinoma:                  e21065
    results from
    protocol-specified
    qualitative
    research           H Kaufman                 N/A             N/A

    Non-Small Cell
    Lung Cancer
    (JAVELIN Solid
    Tumor)

    Comparative study
    of two PD-L1
    expression assays
    in patients with
    non-small cell
    lung cancer
    (NSCLC)            Z Feng        e20581      N/A             N/A

   
                                              Presentation
                                              Date / Time
    Title              Lead Author Abstract # (CDT)           Location
    Tepotinib
    Poster Sessions
    Hepatocellular
    Carcinoma

    Phase Ib trial of
    tepotinib in Asian
    patients with
    advanced
    hepatocellular                 4087       June 3
    carcinoma (HCC):
    Final data
    including
    long-term outcomes S Qin                  8:00-11:30      Hall A     Non-Small Cell
    Lung Cancer

    Phase Ib study of
    tepotinib in
    EGFR-mutant/c-Met-             8547       June 3
    positive NSCLC:
    final data and
    long-term
    responders         Y-L Wu                 8:00-11:30      Hall A

   
    Publications
    Hepatocellular
    Carcinoma

    Final phase Ib
    data for the oral
    c-Met inhibitor
    tepotinib in
    patients with
    previously treated
    advanced
    hepatocellular
    carcinoma          S Faivre    e15676      N/A         N/A     Advanced Lung
    Adenocarcinoma

    Phase II trial of
    the c-Met
    inhibitor
    tepotinib in
    advanced lung
    adenocarcinoma
    with MET exon 14
    skipping mutations PK Paik     20541       N/A         N/A

   
                                               Presentation
                                               Date / Time
    Title              Lead Author  Abstract # (CDT)           Location
    M3814 (DNA-PK)
    Poster Session
    Solid Tumors

    A multicenter
    phase I trial of
    the DNA-dependent               2556       June 5
    protein kinase
    (DNA-PK) inhibitor
    M3814 in patients
    with solid tumors  M van Bussel            8:00-11:30      Hall A     Publication
    Solid Tumors

    A phase Ia/Ib
    trial of the
    DNA-dependent
    protein kinase
    inhibitor
    (DNA-PKi) M3814 in
    combination with
    radiotherapy in
    patients with
    advanced solid
    tumors             B Van Triest e14048     N/A             N/A

   
                       Lead Author

                                              Presentation
                                              Date / Time
    Title                          Abstract # (CDT)           Location
    M7583 (BTKi)
    Publication
    B Cell
    Malignancies

    Phase I/II, first
    in human trial of
    the Bruton's
    tyrosine kinase
    inhibitor (BTKi)
    M7583 in patients
    with B cell
    malignancies       S Rule      e14101     N/A             N/A

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About Avelumab 

Avelumab is a human antibody specific for a protein called PD-L1, or programmed death ligand-1. Avelumab is designed to potentially engage both the adaptive and innate immune systems. By binding to PD-L1, avelumab is thought to prevent tumor cells from using PD-L1 for protection against white blood cells, such as T-cells, exposing them to anti-tumor responses. Avelumab has been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

***Indications

The U.S. Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO^®) for the treatment of (i) metastatic Merkel cell carcinoma (mMCC) in adults and pediatric patients 12 years and older and (ii) patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials. Avelumab is not approved for any indication in any market outside the U.S.

Important Safety Information  

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 include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.

For full prescribing information and medication guide for BAVENCIO, please see http://www.BAVENCIO.com.

About Erbitux^® (cetuximab)  

Erbitux^® is a highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth. Erbitux also targets cytotoxic immune effector cells towards EGFR expressing tumor cells (antibody dependent cell-mediated cytotoxicity, ADCC).

The most commonly reported side effect with Erbitux is an acne-like skin rash. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.

Erbitux has already obtained market authorization in over 90 countries world-wide for the treatment of RAS wild-type metastatic colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck (SCCHN). Merck, KGaA, Darmstadt, Germany licensed the right to market Erbitux, a registered trademark of ImClone LLC, outside the U.S. and Canada from ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company, in 1998.

About M3814 

M3814 is an investigational small-molecule inhibitor of DNA-dependent protein kinase (DNA-PK). DNA-PK is a key enzyme for non-homologous end-joining (NEHJ), the most important DNA double strand break repair pathway (DSB), and could potentially enhance the efficacy of many commonly used DNA-damaging agents such as radiotherapy and chemotherapy. M3814 complements Merck, KGaA, Darmstadt, Germany's extensive DNA damage response (DDR) portfolio and is currently in Phase I studies.

About M7824 

M7824, anti-PD-L1/TGF-ß trap, is an investigational potentially first-in-class bi-functional immunotherapy designed to simultaneously block two immuno-inhibitory pathways (PD-L1 and transforming growth factor beta) that are commonly used by cancer cells to evade the immune system. The aim of this investigational drug is to control tumor growth by restoring and enhancing anti-tumor immune responses. M7824 is currently in Phase I studies for solid tumors.

About Tepotinib 

Tepotinib (also known as MSC2156119J) is an investigational small-molecule inhibitor of the c-Met receptor tyrosine kinase. Alterations of the c-Met signaling pathway are found in various cancer types and correlate with aggressive tumor behavior and poor clinical prognosis. Tepotinib is currently under evaluation in Phase I/II trials.

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.

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