Merck KGaA, Darmstadt, Germany Data at ESMO 2018 Congress Highlight Multiple Therapeutics with Potential to Transform Cancer Care

ESMO Abstract #

Avelumab: LBA6_PR, 659P, 1290P, 1291P, 1282P, 877P; M7824 (TGF -trap/anti-PD-L1): 1048O, 1463P, 1931P, 757P, 643P, 642P, 661P; tepotinib (MET kinase inhibitor): 1377O, 621PD, 698P; M6620: 1437P; M3814: 1845P; M7583: 1014PD; abituzumab: 487P

    --  First presentation of Phase III data for avelumab (plus axitinib) in
        previously untreated, advanced kidney cancer
    --  New and updated data for bifunctional immunotherapy M7824
    --  Results from Phase II trials for tepotinib, including in EGFR
        TKI-resistant NSCLC
    --  Additional pipeline data feature abstracts for a further four innovative
        agents across multiple tumor types with a significant patient need

DARMSTADT, Germany, Oct. 9, 2018 /PRNewswire/ -- Merck KGaA, Darmstadt, Germany, a leading science and technology company which operates its healthcare business in the U.S. and Canada as EMD Serono, today announced that new data from a variety of high-priority clinical development programs will be presented at the ESMO 2018 Congress (European Society for Medical Oncology Annual Meeting), October 19-23, 2018, Munich, Germany.

In the year that Merck KGaA, Darmstadt, Germany celebrates its 350-year anniversary, abstracts at the congress represent a company record with eight therapeutic agents across 14 tumor types, reinforcing Merck KGaA, Darmstadt, Germany's position at the forefront of clinical development in oncology.

"Our data at this year's European Society for Medical Oncology Congress expand our understanding of avelumab in renal cell carcinoma and other tumors, and demonstrate the headway we are making with our pipeline, including bifunctional immunotherapy M7824 and tepotinib," said Luciano Rossetti, Global Head of Research & Development for the Biopharma business of Merck KGaA, Darmstadt, Germany. "We look forward to many more years of real and significant progress towards our vision of transforming the management and treatment of cancer."

Data from the Phase III study JAVELIN Renal 101, evaluating avelumab* in combination with axitinib, compared with sunitinib as initial therapy for patients with advanced renal cell carcinoma (RCC), will be presented for the first time during the Presidential Symposium at ESMO on Sunday, October 21, 2018 at 5:20 PM - 5:35 PM CEST. Avelumab is being jointly developed and commercialized with Pfizer. The results represent the first positive Phase III immunotherapy trial in combination with a tyrosine kinase inhibitor (TKI) in any tumor type, supporting Merck KGaA, Darmstadt, Germany's interest in the potential use of avelumab in combination with currently approved therapies and novel agents. These results will be submitted for publication in a peer-reviewed journal. Other updates include new avelumab data in Merkel cell carcinoma (MCC) and advanced gastric or gastroesophageal junction (GEJ) cancer.

New data for M7824 will be presented from expansion cohorts of two ongoing Phase I clinical trials, including the first tumor-specific data for squamous cell carcinoma of the head and neck (SCCHN), biliary tract cancer, esophageal squamous cell carcinoma and esophageal adenocarcinoma. In addition, updated data for M7824 in patients with gastric cancer and non-small cell lung cancer (NSCLC) will be shared. M7824, discovered in-house at Merck KGaA, Darmstadt, Germany, is an investigational bifunctional immunotherapy designed to combine a transforming growth factor (TGF- ) trap by 'fusing' it with the anti-programmed death ligand-1 (PD-L1) mechanism. To date more than 650 patients with various types of solid tumors have been treated across the program with M7824 and the safety profile is consistent with that observed with other PD-1/PD-L1 inhibitors and previously described skin lesions (keratoacanthomas, SCC, hyperkeratosis) associated with TGF- -inhibiting therapies.

Data for tepotinib** include results from three Phase II trials in epidermal growth factor receptor (EGFR) TKI-resistant NSCLC and advanced hepatocellular carcinoma, providing further evidence of this precision medicine's potential clinical activity in a range of tumors. Tepotinib, discovered in-house at Merck KGaA, Darmstadt, Germany, is an investigational, oral MET inhibitor that is designed to selectively inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations or MET protein overexpression.

Additional pipeline abstracts feature updated data from Merck KGaA, Darmstadt, Germany's comprehensive DNA damage response (DDR) portfolio. These include results from a Phase I trial investigating M6620 (formerly VX-970) in combination with gemcitabine in patients with advanced NSCLC, and combined data from two Phase I trials of DNA-dependent protein kinase inhibitor, M3814. Results will also be shared from a Phase I/II trial of M7583, a Bruton's TKI, in patients with B-cell malignancies, as well as a retrospective analysis of the Phase I/II Poseidon study investigating abituzumab in patients with metastatic colorectal cancer (mCRC).

Data to be presented at the congress for Erbitux(®) will add to the growing body of real-world evidence supporting the therapy's role as a standard of care in RAS wild-type mCRC and first-line recurrent or metastatic SCCHN (R/M SCCHN), and for patients with locally advanced SCCHN (LA SCCHN) who may not be able to tolerate cisplatin-based regimens in full.

*Avelumab is under clinical investigation for the treatment of RCC, MCC, CRC, gastric and GEJ cancer, and has not been demonstrated to be safe and effective for these indications. There is no guarantee that avelumab will be approved for RCC, CRC, gastric or GEJ cancer by any health authority worldwide.

**Tepotinib is the recommended International Nonproprietary Name (INN) for the MET kinase inhibitor MSC2156119J. Tepotinib is currently under clinical investigation and not approved for any use anywhere in the world.

Tepotinib, M7824, M3814, M7583, M6620 and abituzumab 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

Key abstracts supported by Merck KGaA, Darmstadt, Germany, slated for presentation are listed below. In addition, a number of investigator-sponsored studies have been accepted (not listed).


                                                   
            
              Lead Author           Abstract #                       Presentation Date /Time (CEST) 
       
              Location

            
              Title

    ---                                                                                                                                                      ---


            
              Avelumab

    ---


            
              Late-Breaking Abstracts

    ---

             JAVELIN Renal 101: a
              randomized, phase 3 study
              of avelumab + axitinib               
            R Motzer               
     LBA6_PR              
            Sun, Oct 21,                              
       Hall A2 - Room 18
    vs sunitinib as first-line treatment of advanced renal cell
     carcinoma (aRCC)
                                                                                                                 4:30 - 6:10 PM (5:20 - 5:35 PM
                                                                                                                    lecture time)

    ---                                                                                                                                                                            ---


            
              Poster Sessions

    ---

             Avelumab (anti-PD-L1) in                                                                                                                            Hall A3 - Poster Area
              Japanese patients with                                                                                                                              Networking Hub
              advanced gastric or                  
            T Doi                  
     659P                 
            Sun, Oct 21,
    gastroesophageal junction cancer (GC/GEJC): updated results from                                    12:45 - 1:45 PM
    the phase 1b JAVELIN Solid Tumor JPN trial

    ---                                                                                                                                                                            ---

             Avelumab in European                                                                                                                                Hall A3 - Poster Area
              patients (pts) with                                                                                                                                 Networking Hub
              metastatic Merkel cell               
            P Nathan               
     1290P                
            Sun, Oct 21,
    carcinoma (mMCC): experience from an ad hoc expanded access
     program (EAP)                                                                                      12:45 - 1:45 PM

    ---                                                                                                                                                                            ---

             Cost-effectiveness (CE) of                                                                                                                          Hall A3 - Poster Area
              avelumab vs standard care                                                                                                                           Networking Hub
              (SC) for the treatment of
              patients (pts) with
              metastatic Merkel cell
              carcinoma (mMCC)                     
            M Bharmal              
     1291P                
            Sun, Oct 21,
                                                                                                        12:45 - 1:45 PM

    ---                                                                                                                                                                            ---

             Responder analysis based on                                                                                                                         Hall A3 - Poster Area
              patient-reported outcomes                                                                                                                           Networking Hub
              (PROs)                               
            SP D'Angelo            
     1282P                
            Sun, Oct 21,
    and clinical endpoints (CEPs) in patients (pts) with metastatic                                     12:45 - 1:45 PM
    Merkel cell carcinoma (mMCC) treated with avelumab

    ---                                                                                                                                                                            ---

             First-line (1L) or second-                                                                                                                          Hall A3 - Poster Area
              line (2L) avelumab                                                                                                                                  Networking Hub
              monotherapy inpatients
              (pts) with advanced renal
              cell carcinoma (aRCC)                
            UN Vaishampayan        
     877P                 
            Mon, Oct 22,
    enrolled in the phase 1b JAVELIN Solid Tumor trial                                                  12:45 - 1:45 PM

    ---                                                                                                                                                                            ---


                            Title                                    Lead Author         Abstract #                           Presentation Date /Time (CEST)                  Location

    ---                                                                                                                                                      ---


              
                M7824 (TGF  -trap/anti-PD-L1)

    ---


              
                Proffered Paper Session

    ---

               M7824 (MSB0011359C), a
                bifunctional fusion
                protein targeting PD-L1
                and TGF- , in patients
                (pts) with advanced
                SCCHN: results from a
                phase 1 cohort                   
            BC Cho                 
     1048O              
              Mon, Oct 22,                                
       ICM, Room 14B
                                                                                                     2:45 - 4:15 PM (3:00 PM lecture
                                                                                                       time)

    ---                                                                                                                                                                            ---


              
                Poster Sessions

    ---

               Updated results of M7824                                                                                                                          Hall A3 - Poster Area
                (MSB0011359C), a                                                                                                                                  Networking Hub
                bifunctional fusion
                protein targeting TGF- 
                and PD-L1, in second-
                line (2L) NSCLC                  
            L Paz-Ares             
     1463P              
              Sat, Oct 20,
                                                                                                    12:30 - 1:30 PM



    ---                                                                                                                                                                            ---

               Assessment of PD1/                
            T Mrowiec              
     1931P              
              Sun, Oct 21,                                    Hall A3 - Poster Area
                                                                                                                                                                  Networking Hub
    PD-L1 colocalization in hepatocellular carcinoma
     (HCC) using brightfield double labeling and
     quantitative digital image analysis                                                            12:45 - 1:45 PM



    ---                                                                                                                                                                            ---

               M7824 (MSB0011359C), a                                                                                                                            Hall A3 - Poster Area
                bifunctional fusion                                                                                                                               Networking Hub
                protein targeting PD-L1
                and TGF- , in Asian
                patients with pretreated
                biliary tract cancer:
                preliminary results from
                a phase 1 trial                  
            C Yoo                  
     757P               
              Sun, Oct 21,
                                                                                                    12:45 - 1:45 PM

    ---                                                                                                                                                                            ---

               M7824 (MSB0011359C), a                                                                                                                            Hall A3 - Poster Area
                bifunctional fusion                                                                                                                               Networking Hub
                protein targeting PD-L1
                and TGF- , in patients
                with post-platinum
                esophageal adenocarcinoma
                (EAC): preliminary
                results from a phase 1
                cohort                           
            B Tan                  
     643P               
              Sun, Oct 21,
                                                                                                    12:45 - 1:45 PM

    ---                                                                                                                                                                            ---

               Phase 1 study results from                                                                                                                        Hall A3 - Poster Area
                an esophageal squamous                                                                                                                            Networking Hub
                cell carcinoma (ESCC)
                cohort treated with M7824
                (MSB0011359C), a
                bifunctional fusion
                protein targeting
                transforming growth
                factor   (TGF- ) and             
            CC Lin                 
     642P               
              Sun, Oct 21,
    PD-L1                                                                                           12:45 - 1:45 PM

    ---                                                                                                                                                                            ---

               Updated results from a                                                                                                                            Hall A3 - Poster Area
                phase 1 trial of M7824                                                                                                                            Networking Hub
                (MSB0011359C), a
                bifunctional fusion
                protein targeting PD-L1
                and TGF- , in patients
                with pretreated recurrent
                or refractory gastric
                cancer                           
            YJ Bang                
     661P               
              Sun, Oct 21,

                                                                                                    
              12:45 - 1.45 PM

    ---                                                                                                                                                                            ---


                            Title                              Lead Author         Abstract #                           Presentation Date /Time (CEST)                  Location

    ---                                                                                                                                                ---


              
                Tepotinib

    ---


              
                Proffered Paper Session

    ---

               Phase 2 study of tepotinib
                + gefitinib (TEP+GEF) in         
       YL Wu                 
     1377O              
              Fri, Oct 19,                                
       Hall A2, Room 18
    MET-positive (MET+)/epidermal growth factor
     receptor                                                                                 4:00 - 5:30 PM
    (EGFR)-mutant (MT) non-small lung cancer (NSCLC)                                          (4:51 PM lecture time)

    ---                                                                                                                                                                      ---


              
                Poster Discussion

    ---

               Phase 2 trial of tepotinib
                vs sorafenib in Asian
                patients (pts)                   
       BY Ryoo               
     621PD              
              Fri, Oct 19,                                
       Hall B3, Room 21
    with advanced hepatocellular carcinoma (HCC)                                              3:45 - 5:30 PM
                                                                                              (4:25 PM lecture time)

    ---                                                                                                                                                                      ---


              
                Poster Session

    ---

               Phase 2 efficacy and                                                                                                                        Hall A3 - Poster Area
                safety data for the MET                                                                                                                     Networking Hub
                inhibitor tepotinib in           
       T Decaens             
     698P               
              Sun, Oct 21,
    patients (pts) with sorafenib-treated advanced
     hepatocellular carcinoma (HCC)
                                                                                              
              12:45 - 1:45 PM

    ---                                                                                                                                                                      ---



              
                Title                                                                    Lead Author         Abstract #                           Presentation Date /Time (CEST)                  Location

    ---                                                                                                                                                                                      ---


              
                M6620

    ---


              
                Poster Session

    ---


              Phase I dose expansion data for M6620 (formerly VX-970), a first-in-class 
     R Plummer             
     1437P              
              Sat, Oct 20,                                    Hall A3 - Poster Area
                                                                                                                                                                                                  Networking Hub
    ATR inhibitor, combined with gemcitabine (Gem) in patients (pts) with                                                           12:30 - 1:30 PM
    advanced non-small cell lung cancer (NSCLC)

    ---                                                                                                                                                                                                            ---


                            Title                               Lead Author         Abstract #                           Presentation Date /Time (CEST)                  Location

    ---                                                                                                                                                 ---


              
                M3814

    ---


              
                Poster Session

    ---

               Safety, clinical                                                                                                                             Hall A3 - Poster Area
                activity and                                                                                                                                 Networking Hub
                pharmacological
                biomarker evaluation of
                the                            
       M Mau-Sørensen           
     1845P              
              Sat, Oct 20,
    DNA-dependent protein kinase (DNAPK) inhibitor
     M3814: results from two phase I trials                                                    12:30 - 1:30 PM



    ---                                                                                                                                                                       ---


                            Title                    Lead Author          Abstract #                           Presentation Date /Time (CEST)                  Location

    ---                                                                                                                                       ---


              
                M7583

    ---


              
                Poster Session

    ---

               Phase I/II,
                first in human
                trial with
                M7583, a
                Bruton's
                tyrosine kinase
                inhibitor
                (BTKi),                 
      W Jurczak             
     1014PD              
              Sun, Oct 21,                                    Hall B3 - Room 21
    in patients with B cell malignancies                                             4:30 - 5:45 PM



    ---                                                                                                                                                             ---


                            Title                       Lead Author        Abstract #                           Presentation Date /Time (CEST)                  Location

    ---                                                                                                                                        ---


              
                Abituzumab

    ---


              
                Poster session

    ---

               Patient selection                                                                                                                   Hall A3 - Poster Area
                for targeting                                                                                                                       Networking Hub
                integrin with
                abituzumab in
                patients with
                metastatic               
        R Laeufle             
     487P              
              Sun, Oct 21,
    colorectal cancer (mCRC). A retrospective
     analysis of the randomized phase I/II
     Poseidon study                                                                   12:45 - 1:45 PM



    ---                                                                                                                                                              ---

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.(1-3) Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.(3-5) In November 2014, Merck KGaA, Darmstadt, Germany and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Avelumab is currently being evaluated in the JAVELIN clinical development program, which involves at least 30 clinical programs, including seven Phase III trials, and more than 8,600 patients across more than 15 different tumor types. For a comprehensive list of all avelumab trials, please visit clinicaltrials.gov.

Approved Indications in the US

The US Food and Drug Administration (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 (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

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 1,738 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.

About M7824

M7824 is an investigational bifunctional immunotherapy that is designed to bring together a TGF- trap and 'fuse' it with the anti-PD-L1 mechanism. M7824 is designed to simultaneously block the two immunosuppressive pathways - targeting both pathways aims to control tumor growth by potentially restoring and enhancing anti-tumor responses. M7824 is currently in Phase I studies for solid tumors.

About Tepotinib

Tepotinib (MSC2156119J) is an investigational, oral MET inhibitor that is thought to inhibit oncogenic MET receptor signaling caused by MET (gene) alterations, including both MET exon 14 skipping mutations and MET amplifications, or MET protein overexpression. It is a precision medicine and is designed to have a highly selective mechanism of action.

About M6620

M6620 (previously known as VX-970) is an investigational small-molecule thought to inhibit ataxia telangiectasia and Rad3-related protein (ATR). ATR is believed to be a key sensor for DNA damage, activating the DNA damage checkpoint and leading to cell cycle arrest. Inhibition of ATR could potentially enhance the efficacy of DNA-damaging agents, but is also being investigated as a monotherapy against tumors with high levels of replication stress induced by overexpression of oncogenes.

About M3814

M3814 is an investigational small-molecule which is thought to inhibit DNA-dependent protein kinase (DNA-PK). DNA-PK is a key enzyme for non-homologous end-joining (NHEJ), an important DNA double-strand break (DSB) repair pathway. Clinical studies investigating combinations of M3814 with other commonly used DNA-damaging agents such as radiotherapy and chemotherapy are underway.

About M7583

M7583 is an investigational therapy that is thought to be a highly selective covalent inhibitor of Bruton's tyrosine kinase (BTKi) designed to minimize off-target effects.

About Abituzumab

Abituzumab is an investigational pan- integrin inhibiting monoclonal antibody thought to show activity against v 1, 3, 5, 6 and 8 integrin heterodimers. Merck KGaA, Darmstadt, Germany entered into a development agreement with the SFJ Pharmaceuticals Group for abituzumab in metastatic colorectal cancer (mCRC). This collaboration will allow Merck KGaA, Darmstadt, Germany and SFJ to develop the potential of abituzumab in a targeted way, focusing on a patient population that may benefit from the treatment the most.

About Erbitux(®) (cetuximab)

Erbitux(®) is a 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. Based on in vitro evidence, 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 100 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.

All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time they become available on the EMD Group Website. In case you are a resident of the USA or Canada please go to www.emdgroup.com/subscribe to register again for your online subscription of this service as our newly introduced geo-targeting requires new links in the email. You may later change your selection or discontinue this service.

About Merck KGaA, Darmstadt, Germany

Merck KGaA, Darmstadt, Germany, is a leading science and technology company in healthcare, life science and performance materials. Almost 53,000 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 2017, Merck KGaA, Darmstadt, Germany, generated sales of EUR 15.3 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. The only exceptions are the United States and Canada, where the company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.

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