Merck Advances Oncology Portfolio and Pipeline with New and Long-term Data in Multiple Cancers at ESMO 2020

Darmstadt, Germany (ots/PRNewswire) - · New analyses from Phase III JAVELIN Bladder 100 study of BAVENCIO®* assess efficacy across subgroups, patient-reported outcomes and exploratory biomarkers in advanced urothelial cancer

· Overall efficacy data, and analyses of brain metastases and HRQoL for tepotinib? from largest ongoing study in NSCLC harboring MET ex14 skipping

· Long-term follow-up data for novel bifunctional fusion protein targeting TGF-?/PD-L1, bintrafusp alfa?, in NSCLC and BTC demonstrate continued durability of response

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Merck, a leading science and technology company, today announced more than 30 abstracts will be presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 from September 19-21. The abstracts span the Company's clinical program in oncology across several innovative modalities and mechanisms that have the potential to advance treatment across a range of tumor types including biliary tract, lung and urothelial (bladder) cancers.

"Our oncology ambition is to discover innovative therapies with transformative results. The data being presented in urothelial cancer demonstrate this approach in action, where we are seeing promising results for a new first-line maintenance therapeutic option with BAVENCIO® in this form of cancer," said Luciano Rossetti, Global Head of Research & Development for the Biopharma business of Merck. "In addition, long-term follow-up data in advanced lung cancer from two of our in-house developed mechanisms-our oral MET inhibitor, tepotinib, and our first-in-class bifunctional fusion protein immunotherapy targeting TGF-?/PD-L1, bintrafusp alfa-continue to show sustained impact in one of the leading causes of cancer mortality."

Key data highlights at ESMO

Avelumab (BAVENCIO®)

Phase III JAVELIN Bladder 100 (Presentations #699O; 704MO; 745P). Primary results from the JAVELIN Bladder 100 study demonstrated an overall survival (OS) benefit for BAVENCIO vs. best supportive care in the first-line maintenance treatment of advanced urothelial carcinoma, making BAVENCIO the first and only immunotherapy to significantly prolong OS in this setting. Three new abstracts from the JAVELIN Bladder 100 study will be presented at ESMO:

- An oral presentation during the Proffered Paper 1 - GU, non-prostate session scheduled on September 19, 2020 at 5:28pm-5:40pm CEST/11:28am-11:40am EDT, will highlight associations between clinical outcomes and exploratory biomarkers (Presentation #699O) - Two other abstracts provide more information on prespecified subgroup analyses, as well as patient-reported outcomes.

Phase III JAVELIN Head and Neck 100 (Presentation #910O). Primary results from this Phase III study will be presented. The study is a demonstration of our commitment to develop options for patients with squamous cell carcinoma of the head and neck, and the results increase understanding in the field of the role of immunotherapy.

Tepotinib Phase II VISION

(Presentations: #1283P; 1286P; 1347P). Three posters from the largest study in patients with non-small cell lung cancer (NSCLC) harboring MET ex14 skipping treated with tepotinib-an oral, once-daily, highly-selective MET inhibitor. Data presented will highlight:

- Durable clinical activity that has been consistent across clinically relevant subgroups both in treatment-naïve and in previously treated patients as well as in patients with brain metastases as assessed by liquid biopsy or tissue biopsy (Poster #1283P) - Health-related quality of life (HRQOL) has shown to be maintained, with clinically meaningful delays in the time to deterioration of cough, dyspnea, and chest pain (Poster #1286P) - A safety profile consisting of mostly mild-to-moderate adverse events with few treatment discontinuations.

INSIGHT 2 (NSCLC) : The INSIGHT 2 study assessing the combination of osimertinib and tepotinib in patients with EGFR-mutant NSCLC that has developed resistance to first-line osimertinib treatment due to MET amplification is ongoing and actively recruiting patients (Poster #1415TiP).

Bintrafusp alfa (M7824)

Data from the INTR@PID clinical trial program for first-in-class bintrafusp alfa, an investigational bifunctional fusion protein, targeting both TGF-? and PD-L1 pathways, shows promising and durable responses across multiple tumor types including NSCLC and biliary tract cancer (BTC) with a manageable safety profile in Phase I expansion cohorts.

Two long-term follow-up studies assessing efficacy and safety from the INTR@PID clinical trial program will be presented as posters at ESMO 2020:

- INTR@PID Solid Tumor 001 three-year long-term follow-up for 2L treatment of NSCLC (Poster #1272P) - INTR@PID Solid Tumor 008 28-month long-term follow-up in patients with pretreated biliary tract cancer (Poster #73P)

In addition, preliminary analysis will be presented in a mini-oral presentation (#616MO) from a trial conducted by the National Cancer Institute (NCI), the Quick Efficacy Seeking Trial (QuEST), investigating a triple combination therapy (BN-brachyury [BVax] + bintrafusp alfa + N-803) in castration-resistant prostate cancer. Available on demand from September 18 at ESMO.org.

Cetuximab (ERBITUX®) (Presentations: #397O; 402MO; 511P; 960P; 922P)

For the Company's first biology-driven leader ERBITUX, a number of investigator-sponsored studies (ISS), including in combination with BAVENCIO (avelumab), continue to demonstrate its steady role across the continuum of care in metastatic colorectal cancer, and backbone of treatment of squamous cell carcinoma of the head and neck. Data demonstrating the role of ERBITUX as a promising combination partner include an oral presentation investigating avelumab plus cetuximab in pre-treated RAS wild type metastatic colorectal cancer patients as re-challenge strategy: the Phase II CAVE (cetuximab-avelumab) mCRC study. This will be presented during the Proffered Paper GI - colorectal session scheduled on September 19, 2:49pm-3:01pm CEST/8:49am-9:01am EDT (Presentation #397O)

*BAVENCIO is under clinical investigation for the first-line maintenance treatment of advanced UC and not yet approved in any markets outside of the US.

? Tepotinib is the International Nonproprietary Name (INN) for the MET kinase inhibitor MSC2156119J. Tepotinib is currently under clinical investigation in NSCLC and not yet approved in any markets outside of Japan.

? Bintrafusp alfa 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.10-12 In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indications

The European Commission has authorized the use of BAVENCIO in combination with axitinib for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). 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 (MCC).

In the US, BAVENCIO® (avelumab) is indicated for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy. BAVENCIO is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma 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.

BAVENCIO in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC). Additionally, the US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO®) for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

BAVENCIO is currently approved for patients with MCC in 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

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

The special warnings and precautions for use for BAVENCIO monotherapy include infusion-related reactions, as well as immune-related adverse reactions that include pneumonitis and hepatitis (including fatal cases), colitis, pancreatitis (including fatal cases), myocarditis (including fatal cases), endocrinopathies, nephritis and renal dysfunction, and other immune-related adverse reactions. The special warnings and precautions for use for BAVENCIO in combination with axitinib include hepatotoxicity.

The SmPC list of the most common adverse reactions with BAVENCIO monotherapy in patients with solid tumors includes fatigue, nausea, diarrhea, decreased appetite, constipation, infusion-related reactions, weight decreased and vomiting. The list of most common adverse reactions with BAVENCIO in combination with axitinib includes diarrhea, hypertension, fatigue, nausea, dysphonia, decreased appetite, hypothyroidism, cough, headache, dyspnea, and arthralgia.

About Tepotinib

Tepotinib is an oral MET inhibitor that is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations. Discovered and developed in-house at Merck, 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. In March 2020, tepotinib became the first oral MET inhibitor indicated for the treatment of advanced NSCLC harboring MET gene alterations to receive a regulatory approval globally, with the Japanese Ministry of Health, Labour and Welfare (MHLW) approval for the treatment of patients with unresectable, advanced or recurrent NSCLC with MET ex14 skipping alterations. In September 2019, the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for tepotinib in patients with metastatic NSCLC harboring MET ex14 skipping alterations whose disease progressed following platinum-based cancer therapy. Tepotinib is also being investigated in the Phase II INSIGHT 2 study in combination with osimertinib in MET amplified, advanced or metastatic NSCLC harboring activating EGFR mutations that has progressed following first-line treatment with osimertinib.

About Bintrafusp Alfa

Bintrafusp alfa (M7824), discovered in-house at Merck and currently in clinical development through a strategic alliance with GSK, is a potential first-in-class investigational bifunctional fusion protein designed to simultaneously block two immunosuppressive pathways, TGF-? and PD-L1, within the tumor microenvironment. This bifunctional approach is thought to control tumor growth by potentially restoring and enhancing anti-tumor responses. In preclinical studies, bintrafusp alfa has demonstrated antitumor activity both as monotherapy and in combination with chemotherapy. Based on its mechanism of action, bintrafusp alfa offers a potential targeted approach to addressing the underlying pathophysiology of difficult-to-treat cancers.

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]).

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. 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, a leading science and technology company, operates across healthcare, life science and performance materials. Around 57,000 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 2019, Merck generated sales of EUR 16.2 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.

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