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

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DARMSTADT, Germany, October 22, 2018 /PRNewswire=KYODO JBN/ --

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ESMO Abstract #

M7824 (TGF B -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-B 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 (greater than or equal to 1%). In patients with high PD-L1+ expressing tumors (cut-off of

greater than or equal to 80% using the 73-10 assay; greater than or equal to 80% cut-off with 73-10 assay is most comparable to greater than or equal 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-B (TGF-B) 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-B 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-B 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 € 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. 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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SOURCE: Merck