PR85568

DARMSTADT, Germany, Sept. 14, 2020 /PRNewswire=KYODO JBN/ --

-  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.

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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 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

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Source:  Merck