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

PR73843

DARMSTADT, Germany, June 4, 2018 /PRNewswire=KYODO JBN/ --

     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-beta 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-beta (TGF-beta)

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-beta

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-beta 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 (greater than or equal to1%, Ab clone 73-10). In patients

with high PD-L1+ expressing tumors (greater than or equal to80%; Ab clone 73-10

[greater than or equal to80% as measured with Ab clone 73-10 comparable with

tumor proportion score (TPS) greater than or equal to50% 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 greater than or equal

to3 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-beta 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-beta 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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SOURCE: Merck