Merck Presents Updated Results for Bifunctional Immunotherapy M7824 at ESMO 2018 Congress

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ESMO Abstract #

M7824 (TGF ?-trap/anti-PD-L1): 10480, 1463P, 757P, 643P, 642P,
661P, 1931P

- New data presented at the ESMO 2018 Congress include first
disclosure of results for M7824 in advanced squamous cell
carcinoma of the head and neck, biliary tract cancer and esophageal
cancers
- Updated data also being presented include non-small cell lung
cancer and gastric cancer
- M7824 is a bifunctional immunotherapy designed to bring together
transforming growth factor-? and anti-PD-L1 mechanisms

Merck, the vibrant science and technology company, today announced
new and updated results from expansion cohorts of two ongoing M7824
Phase I clinical trials (NCT02517398 and NCT02699515) at the ESMO
(European Society for Medical Oncology) 2018 Congress in Munich,
October 19-23. New data presented include the first presentation of
results for M7824 in advanced squamous cell carcinoma of the head and
neck (SCCHN), biliary tract cancer (BTC) and esophageal cancers
(esophageal squamous cell carcinoma [ESCC] and esophageal
adenocarcinoma [EAC]). In addition, updated data for M7824 in
non-small cell lung cancer (NSCLC) and gastric cancer add to the
growing evidence for M7824's clinical anti-tumor activity in a number
of challenging cancers.

"We are excited to share encouraging updated and new data for
M7824, including four additional difficult-to-treat cancers," said
Luciano Rossetti, Executive Vice President, Head of Global Research &
Development for the Biopharma business of Merck. "The results we've
seen to date will enable us to target those tumors and settings with
the highest potential to impact people living with cancer, as we move
into the next stage of our development program with this bifunctional
immunotherapy."

New data from an ongoing Phase I expansion cohort (32 patients,
NCT02517398) showed signs of promising early clinical activity in
patients with refractory metastatic second-line SCCHN, especially in
HPV-positive SCCHN patients. As presented during the Proffered Paper
Head and Neck cancers session, the overall response rate (ORR) was
15.6%, with a numerically higher ORR in HPV-positive patients (36.4%,
4/11 patients experienced a partial response, with two additional
delayed responses resulting in a 54.5% clinical response rate for the
HPV-positive population. At ASCO 2018, data from the dose escalation
cohort of a Phase I, open-label study in advanced HPV-associated
cancers (including SCCHN) were presented in collaboration with the
National Cancer Institute, which showed that M7824 delivered an ORR
of 41.7% in HPV-positive tumors. These new data from the SCCHN
expansion cohort add to the evidence of encouraging activity in
HPV-positive tumors. A total of 11 patients (34.4%) experienced Grade
3 treatment-related adverse events (TRAEs) and no Grade 4 or 5 TRAEs
were seen. The most common TRAEs were rash (18.8%), asthenia (15.6%),
pruritus (15.6%), hypothyroidism (15.6%), increased alanine
aminotransferase (12.5%), increased aspartate aminotransferase
(12.5%) and skin neoplasm (12.5%).

Updated results (now with longer follow-up and independent review
committee [IRC] assessed data) from an ongoing Phase I trial
(NCT02517398) in patients with previously treated, advanced NSCLC,
demonstrated an ORR of 37.0% (10/27 patients) and progression free
survival of 9.5 months in patients with PD-L1+ tumors (>=1%). In
patients with high PD-L1+ expressing tumors (cut-off of >=80% using
the 73-10 assay; >=80% cut-off with 73-10 assay is most comparable to
>=50% cut-off with the 22C3 test based on internal comparability
studies), ORR was 85.7% (6/7 patients). Grade 3 TRAEs occurred in 23
patients (28.8%) and Grade 4 TRAEs occurred in 2 patients (2.5%):
hypokalemia and decreased blood magnesium and increased amylase and
lipase levels. The most common TRAEs were pruritus (21.3%),
maculopapular rash (18.8%), decreased appetite (12.5%), asthenia
(11.3%) and rash (10.0%).

New data from an ongoing expansion cohort (NCT02699515) in Asian
patients with BTC who had progressed after platinum-based first-line
treatment, demonstrated clinical activity with M7824 treatment. The
ORR among the total of 30 patients was 20%, as assessed by IRC.
Responses were observed across all PD-L1 levels and duration of
response ranged from 8.3 months to 13.9+ months. Grade 3 or higher
TRAEs were experienced by 10 patients (33.3%). The most common TRAEs
were rash (10%) and lipase increase (10%). Three deaths due to
adverse events were reported: one due to septic shock (bacteremia,
etiology unknown) and two due to interstitial lung disease (ILD;
reported term: interstitial pneumonitis). Both patients with ILD were
Japanese, which is consistent with the higher incidence of
drug-induced ILD observed among Japanese patients compared with the
non-Japanese population.[1]

Three additional posters featuring new data from two cohorts of
ongoing Phase I studies in patients with ESCC and advanced EAC
(studies NCT02699515 and NCT02517398 respectively) and updated data
in gastric cancer (NCT02699515) were also presented. These data
provide further indications of the potential of M7824 in cancers with
significant unmet needs.

To date more than 650 patients with various types of solid tumors
have been treated across the program with M7824. The safety profile
is consistent with that observed with other PD-1/PD-L1 inhibitors.
Previously described rash/skin lesions (keratoacanthomas, SCC,
hyperkeratosis) associated with transforming growth factor-? (TGF-?)
inhibiting therapies have also been observed.

Merck has recently initiated a trial to investigate M7824 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 M7824
versus pembrolizumab as monotherapy treatment.

M7824 is an investigational bifunctional immunotherapy that brings
together a TGF-? trap and 'fuses' it with the anti-PD-L1 mechanism.
Designed to simultaneously block the two immunosuppressive pathways,
M7824 is thought to 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.

Notes to Editors

Accepted Merck-supported M7824 abstracts slated for presentation
can be seen here: https://mma.prnewswire.com/media/772385/Merck_ESMO_
Abstract_Table_PRN.pdf

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.

About Biliary Tract Cancer (BTC)

BTC is a collective term for a group of rare and aggressive
gastrointestinal cancers, made up of intrahepatic cholangiocarcinoma
(iCC), extrahepatic cholangiocarcinoma (eCC), and gallbladder
carcinoma (GBC).[2],[3],[4] Surgery is the only curative treatment,
but most patients present with advanced disease and therefore have a
limited survival.[4] Approximately 140,000 cases of BTC are estimated
to occur annually world-wide.[5] However, incidence of BTC varies in
different parts of the world: the incidence of cholangiocarcinomas is
rising in the Western world, with reports of up to 2 in 100,000. By
contrast, in Asian countries, the incidence is much higher.[3] GBC
also has an incidence of 2 in 100,000,?but is much more prevalent in
parts of South America.[3] Collectively these cancers present late in
the majority of patients and long-term outcomes for resectable
patients are poor with median survival in the advanced setting less
than 1?year.[4],[6],[7],[8]

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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
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and Canada, where the company operates as EMD Serono, MilliporeSigma
and EMD Performance Materials.

References

1. Hanaoka M et al, eds. Drug-Induced Lung Injury. Singapore:
Springer; 2017. https://www.springer.com/us/book/9789811044656
2. Blair A B et al. Immunotherapy as a treatment for biliary tract
cancers: A review of approaches with an eye to the future. Current
Problems in Cancer (2017)
https://doi.org/10.1016/j.currproblcancer.2017.10.004
3. Goldstein D et al. New molecular and immunotherapeutic approaches
in biliary cancer. ESMO Open (2017). Published online 2017 Mar 27.
doi: https://dx.doi.org/10.1136%2Fesmoopen-2016-000152
4. Jain A et al. Molecular profiling of biliary tract cancer: a
target rich disease. Journal of Gastrointestinal Oncology (2016)
7(5): 797-803. https://dx.doi.org/10.21037%2Fjgo.2016.09.01
5. Global Burden of Disease Study 2013. The Lancet
2015;385(9963):117-171.
6. GBD. Mortality and causes of death collaborators. global,
regional, and national age-sex specific all-cause and
cause-specific mortality for 240 causes of death, 1990-2013: a
systematic analysis for the global burden of disease study 2013.
Lancet 2013;2015:117-71
7. Marcano-Bonilla et al. Biliary tract cancers: epidemiology,
molecular pathogenesis and genetic risk associations. Chin Clin
Oncol 2016;5:61. no 5. http://dx.doi.org/10.21037/cco.2016.10.09
8. Hezel AF et al. Genetics of biliary tract cancers and emerging
targeted therapies. J Clin Oncol 2010;28:3531-40.
http://dx.doi.org/10.1200/JCO.2009.27.4787

Contact: Brenda Mulligan, +1-978-821-5345

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