omniture

Merck Data at ASCO 2018 to Showcase Progress and Further Optionality of Oncology Pipeline

Merck KGaA
2018-05-17 12:23 1277

DARMSTADT, Germany, May 17, 2018 /PRNewswire/ --

Not intended for UK- or US-based media 

ASCO Abstract #
ERBITUX® (cetuximab): 3521, 3534, e15711; avelumab: 9507, 9537, 9090, 9008, 8563, 3057, 4544, e21531, e13603, e18932, e21623, e21620, e21544; tepotinib (c-Met kinase inhibitor): 9082, 9016; M6620 (ATR inhibitor): 2549, e21048; M3814 (DNA-PK): 2518 M7824 (TGF-ß trap/anti-PD-L1): 3007, 9017, 2566; M2698 (dual p70S6k/Akt inhibitor): 2584

  • Two-year safety and efficacy data in mMCC for avelumab from pivotal JAVELIN Merkel 200 trial 
  • Further data reinforcing commitment to precision medicine and position of ERBITUX® (cetuximab) as a standard of care in mCRC 
  • Early clinical activity in advanced NSCLC and HPV-associated cancers for investigational bifunctional immunotherapy, M7824 
  • Encouraging interim analysis of Phase II data in NSCLC sub-population for c-Met inhibitor, tepotinib 
  • Record number of abstracts accepted across oncology, immuno-oncology and DNA Damage Response (DDR)  

Merck, a leading science and technology company, today announced new data from a number of high priority clinical development programs across its oncology portfolio to be presented at this year's American Society of Clinical Oncology Annual Meeting (ASCO), June 1-5, 2018, Chicago, IL. Abstracts representing seven therapeutic agents and eight tumor types will highlight Merck's position as a key emerging player in oncology.

"This year's data at ASCO demonstrate the potential of our pipeline to really deliver transformative advancements in cancer care," said Luciano Rossetti, Executive Vice President, Head of Global Research & Development at the biopharma business of Merck. "With our strong commitment and focus on the areas we believe in most, Merck's oncology and immuno-oncology pipeline is demonstrating significant potential in the near term with our later-stage priority programs and, in parallel, our early pipeline includes truly innovative programs that could make a real difference for patients."

Data for the legacy brand ERBITUX® continue to build on Merck's heritage in oncology reinforcing its role as a standard of care in RAS wild-type metastatic colorectal cancer (mCRC), the standard of care in first-line recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), and a standard of care for patients with locally advanced SCCHN (LA SCCHN), who may not be able to tolerate cisplatin-based regimens in full.

New data for avelumab* (BAVENCIO®), which is being jointly developed and commercialized with Pfizer, include an oral presentation on two-year results from the pivotal JAVELIN Merkel 200 trial. These long-term results include data on avelumab's duration of response and represent the first study to report long-term survival data for an immunotherapy in metastatic Merkel cell carcinoma (mMCC).

The company will also present further evidence for M7824, an investigational TGF-ß trap/anti-PD-L1 bi-functional immunotherapy fusion protein, from expansion cohorts of the ongoing M7824 Phase I clinical trial (NCT02517398) program. TGF-β, a cytokine released by cells (including tumor cells), suppresses anti-tumor immune responses through a vast number of mechanisms leading to uninhibited tumor growth and metastasis. These data include results in patients with human papillomavirus (HPV)-associated cancers (presented in collaboration with the National Cancer Institute) and data in patients with advanced non-small cell lung cancer (NSCLC). In second-line (2L) NSCLC, signs of clinical activity were seen across PD-L1 expression levels. At the recommended Phase II dose, a confirmed overall response rate (ORR) of 40.7% (11/27) was observed in PD-L1+ patients (>1%), and in patients with high PD-L1 expression (80%; Ab clone 73-10 [>80%=>50% with 22C3]), the ORR was 71.4% (5/7). These data signal the potential of M7824 and provide evidence that combining a transforming growth factor-β (TGF-β) trap with the anti-PD-L1 mechanism in one molecule may generate anti-tumor activity in these patient groups with significant medical need. Treatment with M7824 was well tolerated in both studies and safety data were consistent with that observed in the overall Phase I clinical program. No new safety signals were identified.

For tepotinib**, an investigational highly selective small molecule inhibitor of the c-Met receptor tyrosine kinase, new data to be presented include promising initial results from an ongoing Phase II VISION study providing further indication for the potential of tepotinib in patients living with advanced NSCLC harboring MET exon 14 skipping mutations. Alterations of the c-Met signaling pathway are found in various cancer types and correlate with aggressive tumor behavior and poor clinical prognosis. Based on investigator assessment of data from 15 patients in the study, 60% (9/15) had a confirmed partial response (PR) and 20% (3/15) had stable disease (SD). In addition, independent assessment of 13 patients demonstrated treatment with tepotinib led to a confirmed PR in 46.2% (6/13) and SD in 7.7% (1/13) of patients. In this study, the safety data are consistent with that observed in previous studies and confirm that treatment with tepotinib is well tolerated; no new safety signals were identified.

Tepotinib is an important part of Merck's strategic focus on precision medicines and these results reinforce the company's progress in delivering treatments to those patients more likely to benefit, in order to achieve the best possible outcomes. Both M7824 and tepotinib were discovered in-house at Merck.

Further pipeline updates include Phase I dose escalation data for the investigational DNA-dependent protein kinase (DNA-PK) inhibitor M3814, Phase I triplet therapy with ATR-inhibitor, M6620 +veliparib+cisplatin in advanced solid tumors, and Phase I data for M2698, a potent and selective dual inhibitor of p70S6K and AKT1/3 in the PAM pathway (PI3K/AKT/mTOR pathway). The PAM pathway regulates cell survival and growth and this pathway often displays unusual activity in many human cancers.

*Avelumab is under clinical investigation for treatment of NSCLC, metastatic urothelial carcinoma (mUC) and mesothelioma and has not been demonstrated to be safe and effective for these indications. There is no guarantee that avelumab will be approved for NSCLC, mUC and mesothelioma by any health authority worldwide.

**Tepotinib is the recommended International Nonproprietary Name (INN) for the c-Met kinase inhibitor (MSC2156119J). Tepotinib is currently under clinical investigation and not approved for any use anywhere in the world.

Tepotinib, M7824, M3814, M2698 and M6620 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 

Accepted Merck-supported key 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
Date / Time
(CDT)

Location

Erbitux (cetuximab)

Poster Sessions

Impact of primary tumor
side on outcomes of
every-2-weeks (q2w)
cetuximab + first-line
FOLFOX or FOLFIRI in
patients with RAS wild-
type (wt) metastatic
colorectal cancer
(mCRC) in the phase 2
APEC trial.

Timothy Jay
Price, MBBS,
FRACP, D.H.Sc

3534

Sun, Jun 03, 8:00 AM - 11:30 AM

Hall A

Final overall survival
(OS) analysis of first-line
(1L) FOLFOX-4 plus or
minus cetuximab (cet) in
patients (pts) with RAS
wild-type (wt)
metastatic colorectal
cancer (mCRC) in the
phase 3 TAILOR trial.

Shukui Qin, MD,
BA

3521

Sun, Jun 03, 8:00 AM - 11:30 AM

Hall A

Publication

Cost-effectiveness (CE)
of FOLFIRI (F) +
cetuximab vs F +
bevacizumab in the first-
line treatment of RAS
wild-type (wt)
metastatic colorectal
cancer (mCRC) in
Germany: data from the
FIRE-3 (AIO KRK-0306)
study

Stintzing S, van
Oostrum I,
Pescott CP, et
al.

e15711




Title

Lead Author

Abstract #

Presentation
Date / Time
(CDT)

Location

Avelumab

Oral Presentations

Two-year efficacy and
safety update from
JAVELIN Merkel 200 part
A: A registrational study
of avelumab in
metastatic Merkel cell
carcinoma progressed on
chemotherapy.

Paul Nghiem,
MD, PhD

9507

Mon, Jun 04, 10:12 AM - 10:24 AM

Arie Crown Theater

Avelumab (anti-PD-L1)
in combination with
crizotinib or lorlatinib in
patients with previously
treated advanced
NSCLC: Phase 1b results
from JAVELIN Lung 101.

Alice Tsang
Shaw, MD, PhD

9008

Fri, Jun 01, 4:30 PM - 4:42 PM

Hall D1

Poster Sessions

Avelumab (anti-PD-L1)
in patients with
platinum-treated
advanced NSCLC: 2.5-
year follow-up from the
JAVELIN Solid Tumor
trial.

Arun Rajan, MD

9090

Sun, Jun 03, 8:00 AM - 11:30 AM

Hall A

Phase 1b study of
avelumab in advanced
previously treated
mesothelioma: long-
term follow-up from
JAVELIN Solid Tumor.

Raffit Hassan,
MD

8563

Sun, Jun 03, 8:00 AM - 11:30 AM

Hall A

Second-line avelumab
treatment of patients
(pts) with metastatic
Merkel cell carcinoma
(mMCC): Experience
from a global expanded
access program (EAP).

John WT
Walker, MD,
PhD

9537

Mon, Jun 04, 1:15 PM - 4:45 PM

Hall A

Association of efficacy
and adverse events of
special interest of
avelumab in the JAVELIN
solid tumor and JAVELIN
Merkel 200 trials.

Karen Kelly,
MD, FASCO

 

3057

Mon, Jun 04, 8:00 AM - 11:30 AM

Hall A

SPEAR-bladder (study
informing treatment
pathway decision in
bladder cancer): First-
through third-line time
to treatment failure in
the US.

Gurjyot K.
Doshi, MD

4544

Sat, Jun 02, 8:00 AM - 11:30 AM

Hall A

Publication





Avelumab in patients
with previously treated
metastatic melanoma:
phase 1b results from
the JAVELIN Solid Tumor
trial

Keilholz U,
Mehnert J,
Bauer S, et al.

e21531



Characteristics,
treatment patterns and
safety events from 4
cohorts of advanced or
metastatic cancer
patients based on
healthcare claims data

Russo L,
Esposito D,
Lamy FX, et al.

e13603



Healthcare resource use
and expenditures among
patients with Merkel cell
carcinoma by level of
comorbidity

Kearney M,
Thokagevistk K,
Boutmy E, et al.

e18932



Projecting long-term
survival for avelumab in
patients with refractory
Merkel cell carcinoma

Phatak H,
Proskorovsky I,
Lanitis T, et al.

e21623



Predicting overall
survival in patients (Pts)
with treatment-naive
metastatic Merkel Cell
carcinoma (mMCC)
treated with avelumab

Bullement A,
D'Angelo SP,
Amin A, et al.

e21620



A novel, open-access
data commons for
improved disease

management in Merkel
cell carcinoma patients

Murphy M,
Sartor O,
Bertagnolli M,
et al.

e21544




Title

Lead Author

Abstract #

Presentation
Date / Time
(CDT)

Location

M7824 (beta-trap)

Oral Presentation

Safety and activity of
M7824, a bifunctional
fusion protein targeting
PD-L1 and TGF-beta, in
patients with HPV
associated cancers.

Julius Strauss,
MD

3007

Sat, Jun 02, 5:12 PM - 5:24 PM

Hall B1

Poster Discussion

Results from a second-
line (2L) NSCLC cohort
treated with M7824
(MSB0011359C), a
bifunctional fusion
protein targeting TGF-
beta and PD-L1.

Luis G. Paz-
Ares, MD, PhD

9017

Sun, Jun 03, 11:30 AM - 12:45 PM

Arie Crown Theatre

Poster Session





Selection of the
recommended phase 2
dose (RP2D) for M7824
(MSB0011359C), a
bifunctional fusion
protein targeting TGF-
beta and PD-L1.

Yulia
Vugmeyster,
PhD

2566

Mon, Jun 04, 8:00 AM - 11:30 AM

Hall A


Title

Lead Author

Abstract #

Presentation
Date / Time
(CDT)

Location

Tepotinib

Poster Discussion

Tepotinib in patients
with advanced non-small
cell lung cancer (NSCLC)
harboring MET exon 14-
skipping mutations:
Phase II trial.

Enriqueta Felip,
MD

9016

Sun, Jun 03, 11:30 AM - 12:45 PM

Arie Crown Theatre

Poster Session

Can duration of response
be used as a surrogate
endpoint for overall
survival in advanced
non-small cell lung
cancer?

Boris M Pfeiffer

9082

Sun, Jun 03, 8:00 AM - 11:30 AM

Hall A


Title

Lead Author

Abstract #

Presentation
Date / Time
(CDT)

Location

M2698

Poster Session

Precision oncology:
Results of a phase I
study of M2698, a
p70S6K/AKT targeted
agent in patients with
advanced cancer and
tumor PI3K/AKT/mTOR
(PAM) pathway
abnormalities.

Apostolia Maria
Tsimberidou,
MD, PhD

2584

Mon, Jun 04, 8:00 AM - 11:30 AM

Hall A


Title

Lead Author

Abstract #

Presentation
Date / Time
(CDT)

Location

M3814

Poster Discussion

A phase Ia/Ib trial of the
DNA-PK inhibitor M3814
in combination with
radiotherapy (RT) in
patients (pts) with
advanced solid tumors:
Dose-escalation results.

Baukelien Van
Triest, MD, PhD

2518

Mon, Jun 04, 3:00 PM - 4:15 PM

S406


Title

Lead Author

Abstract #

Presentation
Date / Time
(CDT)

Location

M6620

Poster Discussion

Phase I trial of the triplet
M6620 (formerly VX970)
+ veliparib + cisplatin in
patients with advanced
solid tumors.

Geraldine Helen
O'Sullivan
Coyne, MD, PhD

2549

Mon, Jun 04, 8:00 AM - 11:30 AM

Hall A

Publication





Safety and tolerability of
intravenous M6620 (VX‑
970) administered with
gemcitabine in subjects
with advanced non-small
cell lung cancer (NSCLC)

Plummer R,
Cook N,
Arkenau H-T,
et al.

e21048

Mon, Jun 04, 8:00 AM - 11:30 AM

Hall A

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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. Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Approved Indications in the US 

The 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 Erbitux® (cetuximab)  

Erbitux® is a highly active 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. 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.

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 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 M2698 

M2698 is an investigational small-molecule which is thought to inhibit p70S6K and Akt. Both targets are part of the PI3K/AKT/mTOR (PAM)pathway, which is often dysregulated in solid tumors.

About tepotinib 

Tepotinib (MSC2156119J) is an investigational small-molecule inhibitor of the c-Met receptor tyrosine kinase. Alterations of the c-Met signaling pathway are found in various cancer types and it is thought to correlate with aggressive tumor behavior and poor clinical prognosis.

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 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.

Contact: Gangolf Schrimpf, +49-6151-72-9591

Investor relations: +49-6151-72-3321

Source: Merck KGaA
collection