DARMSTADT, Germany, Oct. 9, 2018 /PRNewswire/ —

Not intended for distribution in the USA, Canada or UK 

ESMO Abstract #

Avelumab: LBA6_PR, 659P, 1290P, 1291P, 1282P, 877P; M7824 (TGF β-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; Erbitux®(cetuximab): 124P, 484P, 509P, 493P, 521P, 510P, 481P, 486P, 1057P, 1108P, 1068P, 1064P, 1293P

• 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 

Merck, a leading science and technology company, 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 celebrates its 350-year anniversary, abstracts at the congress represent a company record with eight therapeutic agents across 14 tumor types, reinforcing Merck’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. “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’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, is an investigational bifunctional immunotherapy designed to combine a transforming growth factor β (TGF-β) 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-β-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, 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’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 Merck-supported abstracts slated for presentation are listed below. In addition, a number of investigator-sponsored studies have been accepted (not listed).

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 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 

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 M7824 

M7824 is an investigational bifunctional immunotherapy that is designed to bring together a TGF-β 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-αν integrin inhibiting monoclonal antibody thought to show activity against αvβ1, 3, 5, 6 and 8 integrin heterodimers. Merck entered into a development agreement with the SFJ Pharmaceuticals Group for abituzumab in metastatic colorectal cancer (mCRC). This collaboration will allow Merck 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 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.

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About Merck 

Merck 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 generated sales of € 15.3 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 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.

References 

1. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control 2014;21:231-7.
2. Dahan R et al. FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell 2015;28:285-95.
3. Boyerinas B et al. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res 2015;3:1148-57.
4. Kohrt HE et al. Combination strategies to enhance antitumor ADCC. Immunotherapy 2012;4:511-27.
5. Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol Ther 2017;17:515-23.