New subgroup analyses for first-line treatment of advanced renal cell carcinoma with BAVENCIO®* (avelumab) in combination with axitinib

Three-year overall survival data for patients treated first-line with ERBITUX® (cetuximab) plus FOLFOX-4 in metastatic colorectal cancer

Data across several therapeutic agents showcase progress of early- to late-stage pipeline, including tepotinib†, and novel combination.

Merck, a leading science and technology company, today announced that new data representing several key therapeutic agents from its diverse oncology pipeline will be presented at the 2019 European Society for Medical Oncology (ESMO) Congress, September 27–October 1, in Barcelona, Spain.

Spanning multiple tumor types, data being presented include new evidence supporting approved treatments BAVENCIO®* (avelumab) and ERBITUX® (cetuximab), and new research from Merck's early pipeline including novel combinations and the investigational targeted therapy tepotinib†, recently granted Breakthrough Therapy Designation (BTD) by the US Food and Drug Administration (FDA) in patients with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations who progressed following platinum-based cancer therapy. In March 2018, tepotinib's potential was also recognized by the Japanese Ministry of Health, Labour and Welfare (MHLW), which granted SAKIGAKE 'fast-track' designation for tepotinib in advanced NSCLC harboring MET exon 14 skipping alterations.

"Our presence at ESMO underscores our commitment to research and development in highly focused areas within immuno-oncology, precision medicine and DNA damage response," said Luciano Rossetti, Global Head of Research & Development for the Biopharma business of Merck. "We believe that by applying cutting-edge science in our clinical programs we are getting closer to making a difference in patient outcomes."

New data for BAVENCIO® will include two poster discussions from the Phase III JAVELIN Renal 101 study evaluating efficacy of first-line treatment with avelumab in combination with axitinib compared with sunitinib in two clinically relevant subgroups of patients with advanced renal cell carcinoma (RCC): those with sarcomatoid histology and those who did not undergo upfront cytoreductive nephrectomy. Results from JAVELIN Renal 101 supported the recent US FDA approval and the positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for BAVENCIO® plus axitinib for first-line treatment of adult patients with advanced RCC.

ERBITUX® data further reinforce the impact of primary tumor location on three-year overall survival among patients from China with RAS wild-type metastatic colorectal cancer (mCRC) treated with first-line FOLFOX-4 with or without cetuximab from the Phase III TAILOR trial. Additionally, a pooled analysis of patient-level data explores the effect on overall survival of cetuximab in combination with chemotherapy dosed once every two weeks, compared with once-weekly dosing, for first-line treatment in patients with RAS wild-type mCRC. These two sets of results underscore the clinical benefit of cetuximab and add to the growing body of evidence supporting its role in combination with chemotherapy in first-line RAS wild-type mCRC.

New research will be presented from across the company's earlier pipeline, including a pooled analysis of safety data across Phase I and II studies in advanced solid tumors for the investigational oral MET inhibitor tepotinib.

A number of investigator-sponsored studies (ISS) and collaborative research studies (CRS) exploring Merck's pipeline will also be presented at this year's congress, including a late-breaking oral presentation on results from a randomized Phase II study of M6620‡, an investigational ataxia telangiectasia and rad3-related (ATR) kinase inhibitor from the company's comprehensive DNA Damage Response (DDR) portfolio, in combination with gemcitabine compared with gemcitabine alone in platinum-resistant high-grade serous ovarian cancer. The study is sponsored by the National Cancer Institute (NCI) under its Cooperative Research and Development Agreement with Merck for M6620, and these results are the first-ever randomized data to be presented for an ATR inhibitor.

*The combination of BAVENCIO® and axitinib is approved for the first-line treatment of advanced RCC only in the United States and Argentina. There is no guarantee that avelumab in combination with axitinib will be approved for RCC by any other 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.

‡M6620 is currently under clinical investigation and not approved for any use anywhere in the world.

About BAVENCIO® (avelumab)

BAVENCIO® is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO® 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, BAVENCIO® has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.1-3 BAVENCIO® 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 BAVENCIO®.

BAVENCIO® Approved Indications

In September 2017, the European Commission granted conditional marketing authorization for BAVENCIO® as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (mMCC). BAVENCIO® is currently approved for patients with MCC in more than 45 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

In the US, BAVENCIO® (avelumab) in combination with axitinib is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). Additionally, the US FDA granted accelerated approval for 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.

BAVENCIO® Safety Profile from the EU Summary of Product Characteristics (SmPC)

The special warnings and precautions for use for BAVENCIO® include infusion-related reactions and immune-related adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, and other adverse reactions).

The SmPC list of the most common adverse reactions in patients with solid tumors includes fatigue, nausea, diarrhea, decreased appetite, constipation, infusion-related reactions, and weight loss and vomiting.

BAVENCIO® Important Safety Information from the US FDA-Approved Label

The warnings and precautions for avelumab (BAVENCIO®) include immune-mediated adverse reactions (such as pneumonitis and hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions, infusion-related reactions, hepatotoxicity, major adverse cardiovascular events (MACE) [which can be severe and have included fatal cases], and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO® include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash. Common adverse reactions (reported in at least 20% of patients) in patients receiving BAVENCIO® in combination with axitinib include diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Grade 3-4 clinical chemistry and hematology laboratory value abnormalities reported in at least 10% of patients across studies include hyponatremia, lymphopenia, increased gamma-glutamyltransferase, blood triglycerides increased and lipase increased.

Axitinib Important Safety Information from the US FDA Approved Label

In the study of advanced RCC after failure of one prior systemic therapy, the warnings and precautions for axitinib include hypertension, including hypertensive crisis, arterial and venous thrombotic events, hemorrhagic events, cardiac failure, gastrointestinal perforation and fistula, hypothyroidism, wound healing complications, reversible posterior leukoencephalopathy syndrome (RPLS), proteinuria, liver enzyme elevation, hepatic impairment, and fetal harm during pregnancy.

Common adverse events (reported in at least 20% of patients) in patients receiving axitinib were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, weight decreased, vomiting, asthenia, and constipation.

About ERBITUX® (cetuximab)

ERBITUX® is an 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).

Very commonly reported side effects with ERBITUX® include acne-like skin rash, mild to moderate infusion-related reactions and hypomagnesemia.

ERBITUX® has already obtained market authorization in over 100 countries worldwide 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.

About Tepotinib

Tepotinib, discovered in-house at Merck is an investigational oral MET inhibitor that is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, including both MET exon 14 skipping mutations and MET amplifications, or MET protein overexpression. It has been designed to have a highly selective mechanism of action, with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.

Tepotinib is currently being investigated in NSCLC and Merck is actively assessing the potential of investigating tepotinib in combination with novel therapies and in other tumor indications.

About Merck

Merck, a leading science and technology company, operates across healthcare, life science and performance materials. Around 52,000 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 technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2018, Merck generated sales of € 14.8 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 since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Performance Materials.