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Thursday, May 16 2019 - 09:12
Merck Data at ASCO 2019 Showcase Multiple Innovative Molecules with Potential to Impact Unmet Needs in Cancer Care
DARMSTADT, Germany, May 16, 2019, /PRNewswire-AsiaNet/--

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

ASCO Abstract # 
Bintrafusp alfa (bifunctional fusion protein): TPS9114; Tepotinib (MET kinase 
inhibitor): 9005; Discovery: 2567; ERBITUX(R) (cetuximab): 3580; BAVENCIO(R) 
(avelumab): 9569; 101; 4552; 4072

- New biomarker analyses for BAVENCIO(R)* (avelumab) in combination with 
axitinib in first-line renal cell carcinoma (RCC) 
- Data presented across several modalities and mechanisms showcase the 
scientific innovation and diversity of the company's pipeline, which includes 
bintrafusp alfa~ (M7824) and tepotinib^ 

Merck, a leading science and technology company, today announced that data 
across several modalities and mechanisms targeting difficult-to-treat cancers 
will be presented at the 2019 American Society of Clinical Oncology (ASCO) 
Annual Meeting, May 31–June 4, Chicago, IL, US. New data will be presented for 
BAVENCIO(R)* (avelumab) and ERBITUX(R) (cetuximab), including rational 
combinations with chemotherapy, radiation therapy and other targeted agents to 
try to identify new ways to improve patient outcomes. This includes an oral 
presentation of data defining biomarkers that differentiate therapy-specific 
outcomes in patients with advanced renal cell carcinoma (RCC), and who have 
been treated first-line with BAVENCIO(R) (avelumab) in combination with 
axitinib. Abstracts also showcase the scientific innovation and diversity of 
Merck's pipeline, with results from a number of high-priority clinical 
development programs, including tepotinib^, bintrafusp alfa~ (M7824) and the 
company's comprehensive DNA Damage Response (DDR) portfolio. 

"At this year's ASCO meeting we continue to demonstrate the breadth and depth 
of our oncology and immuno-oncology portfolio. We will present examples of the 
latest precision medicine and biomarker research and some of the most exciting 
mechanisms being investigated today, including tepotinib and our first-in-class 
bifunctional fusion protein immunotherapy, bintrafusp alfa," said Luciano 
Rossetti, Global Head of Research & Development for the Biopharma business of 
Merck. "Merck's oncology pipeline has significant promise in the near term 
through our late-stage priority programs, and our early pipeline includes 
several potentially groundbreaking modalities. We look forward to sharing the 
latest science with the global oncology community."

For BAVENCIO(R) (avelumab), Merck will share data from five studies across 
tumor types including Merkel cell carcinoma, RCC, hepatocellular carcinoma and 
urothelial carcinoma. This includes an oral presentation of biomarker analyses 
of baseline tumor samples from the Phase III JAVELIN Renal 101 trial in 
previously untreated patients with advanced RCC. The trial indicated that PD-L1 
expression (equal-to-or-less-than 1% immune cells) was associated with the 
longest progression-free survival (PFS) in the avelumab plus axitinib arm and 
the shortest PFS in the sunitinib arm (HR, 0.63; 95% CI, 0.49, 0.81). An 
analysis of relevant gene expression signatures (GES) indicated that in the 
avelumab plus axitinib arm, PFS was enhanced in immune GES–positive patients vs 
those in the negative group (HR, 0.63; 95% CI, 0.46, 0.86; 2-sided p=0.004), 
and vs those in an independent dataset (JAVELIN Renal 100; Choueiri, Lancet 
Oncol, 2018) (HR, 0.46; 95% CI, 0.20, 1.05; 2-sided p=0.064). The combination 
demonstrated a safety and tolerability profile consistent with the known safety 
profiles of each drug alone. The most common adverse reactions 
(equal-to-or-less-than 20%) were diarrhea, fatigue, hypertension, 
musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, 
dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, 
dyspnea, abdominal pain, and headache. Serious adverse reactions occurred in 
35% of patients receiving BAVENCIO(R) (avelumab) in combination with axitinib. 
The incidence of major adverse cardiovascular events (MACE) was higher with 
BAVENCIO(R) (avelumab) in combination with axitinib vs sunitinib.

ERBITUX(R) (cetuximab) data from a retrospective analysis of overall survival 
by subsequent therapy in patients with RAS wild-type metastatic colorectal 
cancer from the Phase III EPIC study will be presented, to evaluate the effect 
of post-study therapies (with ERBITUX(R) without ERBITUX(R), or no subsequent 
therapy) on OS. 
A number of the molecules to be featured were discovered in-house at Merck. 
This includes tepotinib, an oral MET inhibitor designed to inhibit the 
oncogenic MET receptor signaling caused by MET (gene) alterations, and 
bintrafusp alfa, a bifunctional fusion protein designed to simultaneously 
target two immuno-suppressive pathways. Merck's partnership with GSK to jointly 
develop and commercialize bintrafusp alfa, announced in February 2019, is part 
of the company's strategic approach to oncology R&D. Together, Merck and GSK 
aim to rapidly and efficiently progress this molecule, which represents a 
potential step change in the treatment of cancer. 

For tepotinib, promising updated results from the ongoing Phase II VISION study 
in 85 patients with non-small cell lung cancer (NSCLC) with MET exon 14 
skipping mutations (identified by liquid biopsy [LBx] or tumor biopsy [TBx]) 
will be shared. Results show an overall response rate (ORR) of 51.4% for LBx 
patients (independent review committee [IRC]-assessed) or 63.9% 
(investigator-assessed). The ORR for TBx patients was 41.5% (IRC-assessed) or 
58.5% (investigator-assessed). Median duration of response was 9.8 
(IRC-assessed) or 17.1 months (investigator-assessed) for LBx patients and 12.4 
(IRC-assessed) or 14.3 months (investigator-assessed) for TBx patients. Any 
grade treatment-related adverse events (TRAEs) reported by 
equal-to-or-less-than 10% of 69 patients evaluable for safety were peripheral 
edema (47.8%), diarrhea (18.8%), nausea (15.9%) and asthenia (10.1%). No Grade 
4 or 5 TRAEs were observed. TRAEs led to permanent discontinuation in two 
(2.9%) patients (one interstitial lung disease, one diarrhea and nausea). These 
data continue to mature, and an updated data cut from the VISION study will be 
given as an oral presentation at the ASCO meeting on Monday, June 3.

For bintrafusp alfa, a trial-in-progress poster will be shared on the 
open-label study of bintrafusp alfa vs pembrolizumab as a first-line treatment 
in patients with PD-L1-expressing advanced NSCLC. 

Merck takes a personalized approach to R&D, and precision medicine has long 
been a priority. Abstracts being presented at ASCO also include biomarker 
research programs that aim to help identify the patients most likely to benefit 
from specific treatments so they can achieve the best possible medical outcomes.

*The combination of BAVENCIO and axitinib is approved for the first-line 
treatment of advanced RCC only in the United States. 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.

~Bintrafusp alfa is the proposed International Nonproprietary Name (INN) for 
the bifunctional immunotherapy M7824. Bintrafusp alfa is currently under 
clinical investigation and not approved for any use anywhere in the world.

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 

Biomarker analyses from 
JAVELIN Renal 101: 
avelumab + axitinib 
(A+Ax) vs sunitinib (S) 
in advanced renal cell 
carcinoma (aRCC)
T.K. Choueiri
Sat, Jun 1, 8:00 
AM – 9:30 AM 
(8:12 AM – 8:24 
AM lecture time)
Hall D1

Poster Sessions
5-factor prognostic 
model for survival of 
patients with metastatic 
urothelial carcinoma 
receiving 3 different 
post-platinum PD-L1 
G. Sonpavde
Mon, Jun 3, 1:15 
PM – 4:15 PM 
Hall A

First-line avelumab + 
axitinib in patients with 
advanced hepatocellular 
carcinoma: results from 
a phase 1b trial (VEGF 
Liver 100)
M. Kudo
Mon, Jun 3, 8:00 
AM – 11:00 AM
Hall A

Integrative molecular 
analysis of metastatic 
Merkel cell carcinoma to 
identify predictive 
biomarkers of response 
to avelumab
S. Georges
Mon, Jun 3, 1:15 
PM – 4:15 PM
Hall A

Bintrafusp Alfa
Poster Session
Randomized open-label 
study of M7824 vs 
pembrolizumab as first-
line (1L) treatment in 
patients with PD-L1 
expressing advanced 
non-small cell lung 
cancer (NSCLC)
L. Paz-Ares
Sun, Jun 2, 8:00 
AM – 11:00 AM
Hall A

Poster Session
contribution and 
independence of multiple 
biomarkers for 
predicting response to 
P.K. Shah
Sat, Jun 1, 8:00 
AM – 11:00 AM
Hall A

ERBITUX(R) (cetuximab)
Poster Session

Retrospective Analysis of 
Overall Survival (OS) by 
Subsequent Therapy in 
Patients With RAS-Wild-
type (wt) Metastatic 
Colorectal Cancer 
(mCRC) Receiving 
Cetuximab ± Irinotecan 
A. Sobrero
Mon, Jun 3, 8:00 
AM – 11:00 AM
Hall A

Oral Session
Phase II study of 
tepotinib in 
NSCLC patients with 
METex14 mutations
P.K. Paik
Mon, Jun 3, 8:00 AM – 
11:00 AM (9:24 
AM – 9:36 AM 
lecture time)
Hall B1

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 
add 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 other tumor indications.

About Bintrafusp Alfa (M7824) 

Bintrafusp alfa is an investigational bifunctional immunotherapy that is 
designed to combine a TGF-BETA trap with the anti-PD-L1 mechanism in one fusion 
protein. Bintrafusp alfa is designed to combine co-localized blocking of the 
two immuno-suppressive pathways – targeting both pathways aims to control tumor 
growth by potentially restoring and enhancing anti-tumor responses. Bintrafusp 
alfa is currently in Phase I studies for solid tumors, as well as a randomized 
Phase II trial to investigate bintrafusp alfa compared with pembrolizumab as a 
first-line treatment in patients with PD-L1 expressing advanced NSCLC. The 
multicenter, randomized, open-label, controlled study is evaluating the safety 
and efficacy of bintrafusp alfa versus pembrolizumab as a monotherapy 

To date, nearly 700 patients have been treated with bintrafusp alfa across more 
than 10 tumor types in Phase I studies. Encouraging data from the ongoing Phase 
I studies indicates bintrafusp alfa's potential safety and clinical anti-tumor 
activity across multiple types of difficult-to-treat cancers, including 
advanced NSCLC, human papillomavirus-associated cancers, biliary tract cancer 
and gastric cancer. In addition, in pre-clinical studies bintrafusp alfa 
demonstrated superior anti-tumor activity, compared with anti-PD-L1 alone or 
with anti-PD-L1 and TGF-BETA trap when co-administered. In total, eight 
high-priority immuno-oncology clinical development studies are ongoing or 
expected to commence in 2019, including studies in non-small cell lung and 
biliary tract cancers.

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.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 

The clinical development program for avelumab, known as JAVELIN, involves at 
least 30 clinical programs and about 10,000 patients evaluated across more than 
15 different tumor types. These tumor types include RCC, 
gastric/gastro-esophageal junction cancer, head and neck cancer, Merkel cell 
carcinoma, non-small cell lung cancer, and urothelial carcinoma.

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 (MCC). 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 

BAVENCIO(R) (avelumab) in combination with axitinib is indicated in the US for 
the first-line treatment of patients with advanced renal cell carcinoma (RCC).

In the US, the 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(R) 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.
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(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 

Very commonly reported side effects with Erbitux(R) include acne-like skin 
rash, mild to moderate infusion-related reactions and hypomagnesemia.

Erbitux(R) has already obtained market authorization in 114 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. 

1.	Dolan DE, et al. Cancer Control 2014;21:231–7. 
2.	Dahan R, et al. Cancer Cell 2015;28:285–95. 
3.	Boyerinas B, et al. Cancer Immunol Res 2015;3:1148–57. 
4.	Kohrt HE, et al. Immunotherapy 2012;4:511–27. 
5.	Hamilton G, et al. Expert Opin Biol Ther 2017;17:515–23.

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Merck, a leading science and technology company, operates across healthcare, 
life science and performance materials. Around 52,000 employees work to make a 
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joyful and sustainable ways to live. From advancing gene editing technologies 
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sales of EUR 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 
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