Merck Presents Updated Clinical Results for Bifunctional Immunotherapy M7824 at ASCO 2018

Darmstadt, Germany (ots/PRNewswire) -

ASCO Abstract #

M7824 (TGF-ß trap/anti-PD-L1): 3007, 9017, 2566,
TPS3130; Tepotinib (c-Met kinase inhibitor): 9082, 9016; M2698 (dual
p70S6k/Akt inhibitor): 2584; M6620 (ATR inhibitor): 2549; M3814
(DNA-PK): 2518

Not intended for UK- or US-based media

- M7824 is an investigational immunotherapy that is designed to bring
together both anti-transforming growth factor-? and anti-PD-L1
mechanisms
- Data to be presented at ASCO 2018 show M7824's anti-tumor activity
in patients with advanced non-small cell lung cancer and advanced
human papillomavirus associated cancers
- M7824 continues to be explored in tumors and settings where
addressing both mechanisms could lead to improved clinical
outcomes

Merck, a leading science and technology company, today announced
results from expansion cohorts of the ongoing M7824 Phase I clinical
trial (NCT02517398) program at the American Society of Clinical
Oncology (ASCO) 2018 Annual Meeting in Chicago, June 1-5, 2018. These
data include results in patients with advanced non-small cell lung
cancer (NSCLC) and in human papillomavirus (HPV) associated cancers
(NCT03427411), presented in collaboration with the National Cancer
Institute (NCI), providing further evidence that bringing together a
transforming growth factor-? (TGF-?) trap with the anti-PD-L1
mechanism may generate clinically relevant anti-tumor activity.

"M7824's dual approach to fighting cancer, which brings together a
TGF-? trap with the anti-PD-L1 mechanism, complements our existing
immuno-oncology portfolio," said Luciano Rossetti, M.D., Global Head
of Research & Development at the biopharma business of Merck. "The
unique design of this fusion protein offers the potential to
optimally engage the TGF-? pathway. This is one example of the
creative approaches we are taking to address challenging cancers
where we believe we can deliver a transformational change for
patients."

In patients with second line (no prior immunotherapy) advanced
NSCLC from the cohort of the ongoing Phase I clinical trial
(NCT02517398), signs of clinical activity were seen across PD-L1
expression levels. At the recommended Phase II dose (1200 mg every 2
weeks), an investigator-assessed confirmed overall response rate
(ORR) of 40.7% (11/27 patients) was observed in patients with PD-L1+
tumors (>=1%, Ab clone 73-10). In patients with high PD-L1+
expressing tumors (>=80%; Ab clone 73-10 [>=80% as measured with Ab
clone 73-10 comparable with tumor proportion score (TPS) >=50% with
22C3]), ORR was 71.4% (5/7 patients). A median progression-free
survival (PFS) of 6.8 months was observed for PD-L1+ patients (1200
mg every 2 weeks) and the median PFS was not reached for the high
PD-L1-expressing population owing to the number of patients still
responding at the time of analysis. Safety data in this study were
consistent with those observed in the overall M7824 Phase I clinical
program. The most common treatment-related adverse events (TRAEs)
were pruritus (20.0%), maculopapular rash (18.8%) and decreased
appetite (12.5%). Grade 3 TRAEs were experienced by 21 patients
(26.3%), Grade 4 TRAEs occurred in 2 patients (2.5%). The most common
events were skin and subcutaneous tissue disorders. Eight patients
(10%) discontinued treatment due to TRAEs.

From the ongoing Phase I, open-label trial NCT03427411 (presented
in collaboration with the NCI), signs of tumor burden reduction were
seen in 47% (8/17 patients) of patients with advanced HPV associated
cancers, including cervical, anal, or head and neck squamous cell
carcinoma, enrolled in the dose escalation part of the study. The ORR
was 35.3% in patients with HPV associated cancer and 41.7% (including
1 patient with response post-pseudoprogression) in patients with
proven HPV-positive disease (12 patients). Safety data in this study
were consistent with those observed in the broader M7824 clinical
program. A total of 4 patients (23.5%) experienced Grade >=3 TRAEs,
including colitis, cystitis, gastroparesis, pleural effusion and
hypokalemia (Grade 4); notably, 3 of these patients had tumor burden
reduction. No other Grade 4 or 5 TRAEs were seen.

M7824 is an investigational bifunctional immunotherapy that brings
together a TGF-? trap and 'fuses' it with the anti-PD-L1 mechanism.
M7824 is designed to simultaneously block the two immunosuppressive
pathways and control tumor growth by potentially restoring and
enhancing anti-tumor responses. M7824 is an important part of a novel
combination approach that seeks to harness the power of the immune
system and address the tremendously complex nature of
difficult-to-treat tumors such as NSCLC and HPV associated cancers.
These data build on a number of recent readouts for M7824, including
preliminary data in gastric cancer at the ASCO 2018 Gastrointestinal
Cancers Symposium. Merck will present data from additional cohorts in
hard-to-treat cancer types in the coming year.

In addition to M7824, data from a number of high-priority clinical
development programs are also being presented at ASCO 2018, including
tepotinib (NSCLC), M2698 (advanced tumors) and two molecules from the
DNA Damage Response portfolio (advanced solid tumors).

Merck is committed to exploring an array of targets and taking
creative scientific approaches to developing novel therapies for
hard-to-treat cancers. With the belief that rational combination is
key to the development of potential new and more efficacious
treatment options, the company has a particular focus on combination
treatment approaches, whether it be with chemotherapy/radiotherapy,
other targeted therapies and/or immunotherapies from its own or
partners' portfolios.

M7824 at ASCO

Presentation
Date / Time
Title Lead Author Abstract # (CDT)
Location

M7824

Poster Discussion

Results from a
second-line (2L)
NSCLC cohort
treated with
M7824
(MSB0011359C), a
bifunctional
fusion protein Sun, Jun 03,
targeting PD-L1 Luis G. 11:30 a.m. -
and TGF-beta Paz-Ares 9017 12:45 p.m.
Arie Crown Theater

Oral Presentation

Safety and
activity of
M7824, a
bifunctional
fusion protein
targeting PD-L1
and TGF- beta, in
patients with HPV Sat, Jun 02,
associated Julius 5:12 p.m. - 5:24
cancers Strauss 3007 p.m.
Hall B1

Poster Session

Selection of the
recommended Phase
2 dose (RP2D) for
M7824
(MSB0011359C), a
bifunctional
fusion protein
targeting Mon, Jun 04,
TGF-beta and Yulia 8:00 a.m. -
PD-L1 Vugmeyster 2566 11:30 a.m.
Hall A

A sequential
cohort study of
combination
immunotherapy
with BN-brachyury
vaccine, M7824,
ALT-803 and
epacadostat in
metastatic
castration-resist
ant prostate Mon, Jun 04,
cancer (mCRPC) 8:00 a.m. -
(QuEST1) Jason Redman TPS3130 11:30 a.m.
Hall A

About M7824

M7824 is an investigational bifunctional immunotherapy that is
designed to bring together a TGF-? 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.

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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.

Contact: Brenda Mulligan +978-821-5345

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