Merck Data at ESMO 2018 Congress Highlight Multiple Therapeutics with Potential to Transform Cancer Care | Brandaktuell - Nachrichten aus allen Bereichen

Merck Data at ESMO 2018 Congress Highlight Multiple Therapeutics with Potential to Transform Cancer Care

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Darmstadt, Germany (ots/PRNewswire) – Not intended for distribution in the USA, Canada or UK

ESMO Abstract #

Avelumab: LBA6_PR, 659P, 1290P, 1291P, 1282P, 877P; M7824 (TGF β-trap/anti-PD-L1):1048O, 1463P, 1931P, 757P, 643P, 642P, 661P; tepotinib (MET kinase inhibitor): 1377O, 621PD, 698P; M6620: 1437P; M3814: 1845P; M7583: 1014PD; abituzumab: 487P; Erbitux®(cetuximab):
124P, 484P, 509P, 493P, 521P, 510P, 481P, 486P, 1057P, 1108P, 1068P, 1064P, 1293P

* First presentation of Phase III data for avelumab (plus axitinib) in previously untreated, advanced kidney cancer

* New and updated data for bifunctional immunotherapy M7824

* Results from Phase II trials for tepotinib, including in EGFR TKI-resistant NSCLC

* Additional pipeline data feature abstracts for a further four innovative agents across multiple tumor types with a significant patient need

Merck, a leading science and technology company, today announced that new data from a variety of high-priority clinical development programs will be presented at the ESMO 2018 Congress (European Society for Medical Oncology Annual Meeting), October 19-23, 2018, Munich, Germany.

In the year that Merck celebrates its 350-year anniversary, abstracts at the congress represent a company record with eight therapeutic agents across 14 tumor types, reinforcing Merck’s position at the forefront of clinical development in oncology.

„Our data at this year’s European Society for Medical Oncology Congress expand our understanding of avelumab in renal cell carcinoma and other tumors, and demonstrate the headway we are making with our pipeline, including bifunctional immunotherapy M7824 and tepotinib,“ said Luciano Rossetti, Global Head of Research & Development for the Biopharma business of Merck. „We look forward to many more years of real and significant progress towards our vision of transforming the management and treatment of cancer.“

Data from the Phase III study JAVELIN Renal 101, evaluating avelumab* in combination with axitinib, compared with sunitinib as initial therapy for patients with advanced renal cell carcinoma (RCC), will be presented for the first time during the Presidential Symposium at ESMO on Sunday, October 21, 2018 at 5:20 PM – 5:35 PM CEST. Avelumab is being jointly developed and commercialized with Pfizer. The results represent the first positive Phase III immunotherapy trial in combination with a tyrosine kinase inhibitor (TKI) in any tumor type, supporting Merck’s interest in the potential use of avelumab in combination with currently approved therapies and novel agents. These results will be submitted for publication in a peer-reviewed journal. Other updates include new avelumab data in Merkel cell carcinoma (MCC) and advanced gastric or gastroesophageal junction (GEJ) cancer.

New data for M7824 will be presented from expansion cohorts of two ongoing Phase I clinical trials, including the first tumor-specific data for squamous cell carcinoma of the head and neck (SCCHN), biliary tract cancer, esophageal squamous cell carcinoma and esophageal adenocarcinoma. In addition, updated data for M7824 in patients with gastric cancer and non-small cell lung cancer (NSCLC) will be shared. M7824, discovered in-house at Merck, is an investigational bifunctional immunotherapy designed to combine a transforming growth factor β (TGF-β) trap by ‚fusing‘ it with the anti-programmed death ligand-1 (PD-L1) mechanism. To date more than 650 patients with various types of solid tumors have been treated across the program with M7824 and the safety profile is consistent with that observed with other PD-1/PD-L1 inhibitors and previously described skin lesions (keratoacanthomas, SCC, hyperkeratosis) associated with TGF-β-inhibiting therapies.

Data for tepotinib** include results from three Phase II trials in epidermal growth factor receptor (EGFR) TKI-resistant NSCLC and advanced hepatocellular carcinoma, providing further evidence of this precision medicine’s potential clinical activity in a range of tumors. Tepotinib, discovered in-house at Merck, is an investigational, oral MET inhibitor that is designed to selectively inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations or MET protein overexpression.

Additional pipeline abstracts feature updated data from Merck’s comprehensive DNA damage response (DDR) portfolio. These include results from a Phase I trial investigating M6620 (formerly VX-970) in combination with gemcitabine in patients with advanced NSCLC, and combined data from two Phase I trials of DNA-dependent protein kinase inhibitor, M3814. Results will also be shared from a Phase I/II trial of M7583, a Bruton’s TKI, in patients with B-cell malignancies, as well as a retrospective analysis of the Phase I/II Poseidon study investigating abituzumab in patients with metastatic colorectal cancer (mCRC).

Data to be presented at the congress for Erbitux® will add to the growing body of real-world evidence supporting the therapy’s role as a standard of care in RAS wild-type mCRC and first-line recurrent or metastatic SCCHN (R/M SCCHN), and for patients with locally advanced SCCHN (LA SCCHN) who may not be able to tolerate cisplatin-based regimens in full.

*Avelumab is under clinical investigation for the treatment of RCC, MCC, CRC, gastric and GEJ cancer, and has not been demonstrated to be safe and effective for these indications. There is no guarantee that avelumab will be approved for RCC, CRC, gastric or GEJ cancer by any 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.

Tepotinib, M7824, M3814, M7583, M6620 and abituzumab are under clinical investigation and have not been proven to be safe and effective. There is no guarantee any product will be approved in the sought-after indication by any health authority worldwide.

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 Author Abstract # Presentation Location

Date / Time (CEST) Avelumab
Late-Breaking Abstracts
JAVELIN Renal 101: R Motzer LBA6_PR Sun, Oct 21, Hall A2 –
a randomized, 4:30 – 6:10 PM Room 18
phase 3 study of (5:20 – 5:35 PM avelumab + lecture time) axitinib vs
sunitinib as
first-line
treatment of
advanced renal
cell carcinoma
(aRCC)

Poster Sessions
Avelumab T Doi 659P Sun, Oct 21 Hall A3 –
(anti-PD-L1) in 12:45 – 1:45 PM Poster Area
Japanese patients
Networking Hub
with advanced
gastric or
gastroesophageal
junction cancer
(GC/GEJC): updated
results from the
phase 1b JAVELIN
Solid Tumor JPN
trial
Avelumab in P Nathan 1290P Sun, Oct 21, Hall A3 –
European patients 12:45 – 1:45 PM Poster Area
(pts) with
Networking Hub
metastatic Merkel
cell carcinoma
(mMCC): experience
from an ad hoc
expanded access
program (EAP)
Cost-effectiveness M Bharmal 1291P Sun, Oct 21, Hall A3 –
(CE) of avelumab 12:45 – 1:45 PM Poster Area
vs standard care
Networking Hub
(SC) for the
treatment of
patients (pts)
with metastatic
Merkel cell
carcinoma (mMCC)
Responder analysis SP D’Angelo 1282P Sun, Oct 21, Hall A3 –
based on 12:45 – 1:45 PM Poster Area
patient-reported
Networking Hub
outcomes (PROs)
and clinical
endpoints (CEPs)
in patients (pts)
with metastatic
Merkel cell
carcinoma (mMCC)
treated with
avelumab
First-line (1L) or UN Mon, Oct 22, Hall A3 –
second-line (2L) Vaishampayan 877P 12:45 – 1:45 PM Poster Area
avelumab
Networking Hub
monotherapy in
patients (pts)
with advanced
renal cell
carcinoma (aRCC)
enrolled in the
phase 1b JAVELIN
Solid Tumor trial

Title Lead Author Abstract # Presentation Location
Date / Time
(CEST M7824 (TGF β-trap/anti-PD-L1)

Proffered Paper Session
M7824 BC Cho 1048O Mon, Oct 22, ICM, Room
(MSB0011359C), a 2:45 -4:15 PM 14B
bifunctional (3:00 PM fusion protein lecture time)
targeting PD-L1
and TGF-β, in
patients (pts)
with advanced
SCCHN: results
from a phase 1
cohort
Poster Sessions
Updated results of L Paz-Ares 1463P Sat, Oct 20, Hall A3 –
M7824 12:30 -1:30 PM Poster Area
(MSB0011359C), a
Networking Hub
bifunctional
fusion protein
targeting TGF-β
and PD-L1, in

second-line (2L)
NSCLC
Assessment of PD1/ T Mrowiec 1931P Sun, Oct 21, Hall A3 –
PD-L1 12:45 -1:45 PM Poster Area
colocalization in
Networking Hub
hepatocellular
carcinoma (HCC)
using brightfield
double labeling
and quantitative
digital image
analysis
M7824 C Yoo 757P Sun, Oct 21, Hall A3 –
(MSB0011359C), a 12:45 -1:45 PM Poster Area
bifunctional
Networking Hub
fusion protein
targeting PD-L1
and TGF-β, in
Asian patients
with pretreated
biliary tract
cancer:
preliminary
results from a
phase 1 trial
M7824 B Tan 643P Sun, Oct 21, Hall A3 –
(MSB0011359C), a 12:45 -1:45 PM Poster Area
bifunctional
Networking Hub
fusion protein
targeting PD-L1
and TGF-β, in
patients with
post-platinum
esophageal
adenocarcinoma
(EAC): preliminary
results from a
phase 1 cohort
Phase 1 study CC Lin 642P Sun, Oct 21, Hall A3 –
results from an 12:45 -1:45 PM Poster Area
esophageal
Networking Hub
squamous cell
carcinoma (ESCC)
cohort treated
with M7824
(MSB0011359C), a
bifunctional
fusion protein
targeting
transforming
growth factor β
(TGF-β) and
PD-L1
Updated results YJ Bang 661P Sun, Oct 21, Hall A3 –
from a phase 1 12:45 -1:45 PM Poster Area
trial of M7824
Networking Hub
(MSB0011359C), a
bifunctional
fusion protein
targeting PD-L1
and TGF-β, in
patients with
pretreated
recurrent or
refractory gastric
cancer

Title Lead Author Abstract # Presentation Location
Date / Time (CEST) Tepotinib
Proffered Paper Session
Phase 2 study of YL Wu 1377O Fri, Oct 19, Hall A2,
tepotinib + 4:00 – 5:30 PM Room 18
gefitinib (4:51 PM (TEP+GEF) in lecture time) MET-positive
(MET+)/epidermal
growth factor
receptor
(EGFR)-mutant (MT)
non-small lung
cancer (NSCLC)
Poster Discussion
Phase 2 trial of BY Ryoo 621PD Fri, Oct 19, Hall B3,
tepotinib vs 3:45 – 5:30 PM Room 21
sorafenib in Asian (4:25 PM patients (pts) lecture time) with advanced
hepatocellular
carcinoma (HCC)
Poster Session
Phase 2 efficacy T Decaens 698P Sun, Oct 21, Hall A3 –
and safety data 12:45 – 1:45 PM Poster Area
for the MET
Networking Hub
inhibitor
tepotinib in
patients (pts)
with
sorafenib-treated
advanced
hepatocellular
carcinoma (HCC)

Title Lead Author Abstract # Presentation Location
Date / Time
(CEST)
M6620
Poster Session
Phase I dose R Plummer 1437P Sat, Oct 20, Hall A3 –
expansion data for 12:30 – 1:30 PM Poster Area
M6620 (formerly
Networking Hub
VX-970), a
first-in-class ATR
inhibitor,
combined with
gemcitabine (Gem)
in patients (pts)
with advanced
non-small cell
lung cancer
(NSCLC)

Title Lead Author Abstract # Presentation Location
Date / Time (CEST)
M3814
Poster Session
Safety, clinical M Mau-Sørensen 1845P Sat, Oct 20, Hall A3 –
activity and 12:30 – 1:30 PM Poster Area
pharmacological
Networking Hub
biomarker
evaluation of the
DNA-dependent
protein kinase
(DNAPK) inhibitor
M3814: results
from two phase I
trials

Title Lead Author Abstract # Presentation Location
Date / Time
(CEST)
M7583
Poster Session
Phase I/II, first W Jurczak 1014PD Sun, Oct 21, Hall B3 –
in human trial 4:30 – 5:45 PM Room 21
with M7583, a
Bruton’s tyrosine
kinase inhibitor
(BTKi), in
patients with B
cell malignancies

Title Lead Author Abstract # Presentation Location
Date / Time
(CEST)
Abituzumab
Poster session
Patient selection R Laeufle 487P Sun, Oct 21,
Hall A3 –
for targeting 12:45 – 1:45 PM Poster Area
integrin with
Networking Hub
abituzumab in
patients with
metastatic
colorectal cancer
(mCRC). A
retrospective
analysis of the
randomized phase
I/II Poseidon
study

Title Lead Author Abstract # Presentation Location
Date / Time (CEST)
Erbitux
Poster Sessions
Association of L Miller-Phillips 124P Sat, Oct 20, Hall A3 –
microRNA-21 12:30 – 1:30 PM Poster Area
(miR-21) with
Networking Hub
efficacy of
cetuximab (cet)
and bevacizumab
(bev) in patients
with metastatic
colorectal cancer
(mCRC) within the
FIRE-3 study (AIO
KRK-0306)
Retrospective RAS A Sobrero 484P Sun, Oct 21, Hall A3 –
analysis of the 12:45 – 1:45 PM Poster Area
EPIC trial:
Networking Hub
Cetuximab plus
irinotecan versus
irinotecan alone
in patients with
third- and
further-line
metastatic
colorectal cancer
Factors DP Modest 509P Sun, Oct 21, Hall A3 –
influencing 12:45 – 1:45 PM Poster Area
conversion to
Networking Hub
resectability and
survival after
resection of
metastases in RAS
WT metastatic
colorectal cancer
(mCRC): analysis
of FIRE-3-
AIOKRK0306
Initial report of E Oki 493P Sun, Oct 21, Hall A3 –
a phase I/II study 12:45 – 1:45 PM Poster Area
of S-1 and
Networking Hub
irinotecan (IRIS)
in combination
with cetuximab in
patients with
wild-type (wt) RAS
metastatic
colorectal cancer
miR-31 as a Y Gaston-Mathé 521P Sun, Oct 21, Hall A3 –
prognostic and 12:45 – 1:45 PM Poster Area
predictive marker
Networking Hub
of disease-free
survival (DFS) in
resected stage III
colon cancer: a
retrospective
analysis of the
PETACC-8 trial
Targeted therapies BC Xing 510P Sun, Oct 21, Hall A3 –
in conversion 12:45 – 1:45 PM Poster Area
therapy in mCRC: A
Networking Hub
systematic review
and meta-analysis
Phase II study of H Osawa 481P Sun, Oct 21, Hall A3 –
cetuximab 12:45 – 1:45 PM Poster Area
rechallenge in
Networking Hub
patients with RAS
wild-type
metastatic
colorectal cancer:
E-rechallenge
trial
Prospective X García-Albéniz 486P Sun, Oct 21, Hall A3 –
biomarker study in 12:45 – 1:45 PM Poster Area
advanced RAS
Networking Hub
wild-type
colorectal cancer.
POSIBA trial.
(GEMCAD 10-02)
Cetuximab + C Le Tourneau 1057P Sun, Oct 21, Hall A3 –
platinum-based 12:45 – 1:45 PM Poster Area
therapy (PBT) as a
Networking Hub
first-line
treatment for
patients with
recurrent/metastat
ic squamous cell
carcinoma of the
head and neck (R/M
SCCHN): an

observational
study (ENCORE)
Can concomitant J Dunst 1108P Sun, Oct 21, Hall A3 –
diseases predict 12:45 – 1:45 PM Poster Area
the compliance
Networking Hub
with cisplatin
plus RT in
patients with
locally advanced
squamous cell
carcinoma of the
head and neck (LA
SCCHN)? An
exploratory
endpoint analysis
of the COMPLY
trial
Cetuximab in JC Ham 1068P Sun, Oct 21, Hall A3 –
combination with 12:45 – 1:45 PM Poster Area
methotrexate (MTX)
Networking Hub
as first-line
treatment in
recurrent or
metastatic (R/M)
squamous cell
carcinoma of the
head and neck
(SCCHN), a phase
Ib – randomized
phase II study
versus single
agent MTX
Cetuximab in M Hecht 1064P Sun, Oct 21, Hall A3 –
combination with 12:45 – 1:45 PM Poster Area
platinum-based
Networking Hub
chemotherapy or
radiotherapy in
patients with
recurrent and/or
metastatic SSCHN
in clinical
routine: Updated
interim results of
the prospective
SOCCER study
Cetuximab in F Peyrade 1293P Sun, Oct 21, Hall A3 –
patients with 12:45 – 1:45 PM Poster Area
unresectable
Networking Hu
cutaneous squamous
cell carcinoma is
safe and effective
– A real-life
analysis

About Avelumab

Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab 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, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.[1]-[3] Avelumab 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 avelumab.

Avelumab is currently being evaluated in the JAVELIN clinical development program, which involves at least 30 clinical programs, including seven Phase III trials, and more than 8,600 patients across more than 15 different tumor types. For a comprehensive list of all avelumab trials, please visit clinicaltrials.gov.

Approved Indications in the US

The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (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.

Important Safety Information from the US FDA Approved Label

The warnings and precautions for BAVENCIO include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO for mMCC and patients with locally advanced or mUC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.

About M7824

M7824 is an investigational bifunctional immunotherapy that is designed to bring together a TGF-β trap and ‚fuse‘ it with the anti-PD-L1 mechanism. M7824 is designed to simultaneously block the two immunosuppressive pathways – targeting both pathways aims to control tumor growth by potentially restoring and enhancing anti-tumor responses. M7824 is currently in Phase I studies for solid tumors.

About Tepotinib

Tepotinib (MSC2156119J) is an investigational, oral MET inhibitor that is thought to inhibit oncogenic MET receptor signaling caused by MET (gene) alterations, including both MET exon 14 skipping mutations and MET amplifications, or MET protein overexpression. It is a precision medicine and is designed to have a highly selective mechanism of action.

About M6620

M6620 (previously known as VX-970) is an investigational small-molecule thought to inhibit ataxia telangiectasia and Rad3-related protein (ATR). ATR is believed to be a key sensor for DNA damage, activating the DNA damage checkpoint and leading to cell cycle arrest. Inhibition of ATR could potentially enhance the efficacy of DNA-damaging agents, but is also being investigated as a monotherapy against tumors with high levels of replication stress induced by overexpression of oncogenes.

About M3814

M3814 is an investigational small-molecule which is thought to inhibit DNA-dependent protein kinase (DNA-PK). DNA-PK is a key enzyme for non-homologous end-joining (NHEJ), an important DNA double-strand break (DSB) repair pathway. Clinical studies investigating combinations of M3814 with other commonly used DNA-damaging agents such as radiotherapy and chemotherapy are underway.

About M7583

M7583 is an investigational therapy that is thought to be a highly selective covalent inhibitor of Bruton’s tyrosine kinase (BTKi) designed to minimize off-target effects.

About Abituzumab

Abituzumab is an investigational pan-αν integrin inhibiting monoclonal antibody thought to show activity against αvβ1, 3, 5, 6 and 8 integrin heterodimers. Merck entered into a development agreement with the SFJ Pharmaceuticals Group for abituzumab in metastatic colorectal cancer (mCRC). This collaboration will allow Merck and SFJ to develop the potential of abituzumab in a targeted way, focusing on a patient population that may benefit from the treatment the most.

About Erbitux® (cetuximab)

Erbitux® is a 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).

The most commonly reported side effect with Erbitux is an acne-like skin rash. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.

Erbitux has already obtained market authorization in over 100 countries world-wide for the treatment of RAS wild-type metastatic colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck (SCCHN). 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 is a leading science and technology company in healthcare, life science and performance materials. Almost 53,000 employees work to further develop technologies that improve and enhance life – from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD televisions. In 2017, Merck generated sales of EUR 15.3 billion in 66 countries.

Founded in 1668, Merck is the world’s oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.

References

1. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control 2014;21:231-7.

2. Dahan R et al. FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell 2015;28:285-95.

3. Boyerinas B et al. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res 2015;3:1148-57.

4. Kohrt HE et al. Combination strategies to enhance antitumor ADCC.
Immunotherapy 2012;4:511-27.

5. Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol Ther 2017;17:515-23.

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