Merck Data at ASCO 2019 Showcase Multiple Innovative Molecules with Potential to Impact Unmet Needs in Cancer Care

Geschrieben am 16-05-2019

Darmstadt, Germany (ots/PRNewswire) -

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® (cetuximab): 3580; BAVENCIO® (avelumab): 9569; 101; 4552;

- New biomarker analyses for BAVENCIO®* (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®* (avelumab)
and ERBITUX® (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®
(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

For BAVENCIO® (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
(>=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 (>=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® (avelumab) in combination with
axitinib. The incidence of major adverse cardiovascular events (MACE)
was higher with BAVENCIO® (avelumab) in combination with axitinib vs

ERBITUX® (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®, without ERBITUX®, 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 >=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

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 listed).

Title Lead Abstract Presentation Location
Author # Date / Time
Oral Session
Biomarker T.K. 101 Sat, Jun 1, Hall D1
analyses from Choueiri 8:00 AM -
JAVELIN Renal 9:30 AM
101: avelumab (8:12 AM -
+ axitinib 8:24 AM
(A+Ax) vs lecture
sunitinib (S) time)
in advanced
renal cell
5-factor G. 4552 Mon, Jun 3, Hall A
prognostic Sonpavde 1:15 PM -
model for 4:15 PM
survival of
patients with
receiving 3
First-line M. Kudo 4072 Mon, Jun 3, Hall A
avelumab + 8:00 AM -
axitinib in 11:00 AM
patients with
results from a
phase 1b trial
(VEGF Liver
Integrative S. 9569 Mon, Jun 3, Hall A
molecular Georges 1:15 PM -
analysis of 4:15 PM
Merkel cell
carcinoma to
biomarkers of
response to
Poster Session
Randomized L. TPS9114 Sun, Jun 2, Hall A
open-label Paz-Ares 8:00 AM -
study of M7824 11:00 AM
as first-line
(1L) treatment
in patients
with PD-L1
non-small cell
lung cancer
Poster Session
Understanding P.K. 2567 Sat, Jun 1, Hall A
contribution Shah 8:00 AM -
and 11:00 AM
of multiple
biomarkers for
response to
Poster Session
Retrospective A. 3580 Mon, Jun 3, Hall A
Analysis of Sobrero 8:00 AM -
Overall 11:00 AM
Survival (OS)
by Subsequent
Therapy in
Patients With
Cancer (mCRC)
Cetuximab ±
Oral Session
Phase II study P.K. 9005 Mon, Jun 3, Hall B1
of tepotinib Paik 8:00 AM -
in NSCLC 11:00 AM
patients with (9:24 AM -
METex14 9:36 AM
mutations lecture

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 other tumor indications.

About Bintrafusp Alfa (M7824)

Bintrafusp alfa is an investigational bifunctional immunotherapy
that is designed to combine a TGF-? 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 treatment.

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-? 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® (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.

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 treatment.

BAVENCIO® (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

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.

Axitinib Important Safety Information from the US FDA Approved

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

Erbitux® 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®, 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


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.

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 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 - Merck is everywhere. In 2018, Merck generated 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 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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