-  New analyses from Phase III JAVELIN Bladder 100 study of BAVENCIO(R)* 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 METex14 skipping 
-  Long-term follow-up data for novel bifunctional fusion protein targeting 
TGF-β/PD-L1, bintrafusp alfa‡, in NSCLC and BTC demonstrate continued 
durability of response

Not intended for UK- US- or Canada-based media

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(R) 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-β/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(R))

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 
METex14 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-β 
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(R)) (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(R) (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(R) (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(R)) 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 METex14 skipping alterations. In September 
2019, the US Food and Drug Administration (FDA) granted Breakthrough Therapy 
Designation for tepotinib in patients with metastatic NSCLC harboring METex14 
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-β 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(R) (cetuximab) 
ERBITUX(R) is an IgG1 monoclonal antibody targeting the epidermal growth factor 
receptor (EGFR). As a monoclonal antibody, the mode of action of ERBITUX(R) 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(R) also targets cytotoxic immune effector cells towards 
EGFR-expressing tumor cells (antibody-dependent cell-mediated cytotoxicity 
[ADCC]).

ERBITUX(R) 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(R), 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 Press Releases are distributed by e-mail at the same time they become 
available on the Merck Website. Please go to www.merckgroup.com/subscribe to 
register online, change your selection or discontinue this service. 

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 16.2 billion Euros 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.

Contact:  
Julissa.Viana@emdserono.com 
Phone: +1 (781) 206 5795 

Logo - https://mma.prnewswire.com/media/1136775/Merck_Logo.jpg 
     
Source:  Merck