Darmstadt, Germany:
Not supposed for US- or Canada-based media
- Late-breaking information spotlight 5-year survival outcomes from Phase II research of the investigational IAP inhibitor xevinapant within the healing setting of unresected LA SCCHN
- Initial outcomes of Phase II INSIGHT 2 research of TEPMETKO plus osimertinib as second-line remedy in EGFR-mutant NSCLC with MET amplification confirmed encouraging indicators of medical exercise with this focused, oral, chemo-sparing routine
- First-in-human outcomes for potential best-in-class investigational ATR inhibitor M1774
Merck, a number one science and know-how firm, right now introduced the newest analysis from the Company’s oncology portfolio and pipeline to be introduced at this 12 months’s European Society of Medical Oncology (ESMO) Annual Meeting, September 9-13, 2022. A complete of 29 abstracts, together with 5 late-breaking oral displays and a pair of extra mini-oral displays, will characteristic information from company- and investigator-sponsored research throughout six authorized or investigational medicines in a number of tumor sorts.
“Our ESMO 2022 data will highlight the strong potential of our innovative pipeline for patients with cancers with significant unmet needs,” mentioned Victoria Zazulina, M.D., Head of Development Unit, Oncology, for the Healthcare business of Merck. “From our IAP inhibitor xevinapant, studied in a curative setting in locally advanced head and neck cancer; through to new data in NSCLC patients with MET amplification and EGFR mutations; to our potentially best-in-class oral ATR inhibitor; we are focused on unlocking novel mechanisms of action that exploit the vulnerabilities of cancer.”
The firm’s late-breaking information at the congress characteristic five-year total survival (OS) outcomes from a Phase II research of the IAP (Inhibitor of Apoptosis Protein) inhibitor xevinapant in sufferers with unresected domestically superior squamous cell carcinoma of the top and neck [Mini Oral #LBA33]. Patients who acquired xevinapant plus chemoradiotherapy (CRT) had improved efficacy outcomes in contrast with those that acquired placebo with CRT.
Additional late-breaking outcomes embrace preliminary outcomes from the Phase II INSIGHT 2 trial of TEPMETKO® (tepotinib) plus osimertinib within the remedy of sufferers with EGFR-mutant non-small cell lung most cancers (NSCLC) with MET amplification (METamp) after development on first-line remedy with osimertinib [Proffered Paper #LBA52]. The confirmed total response charge (ORR) was 54.5% (95% CI, 32.2, 75.6) in 22 sufferers with METamp detected by FISH (MET GCN ≥5 and/or MET/CEP7 ≥2) in tissue biopsy who acquired tepotinib plus osimertinib and have been adopted for at least 9 months, with six of 12 responders nonetheless on remedy. Among the 48 sufferers adopted for at least three months, ORR was 45.8% (95% CI, 31.4, 60.8). The most typical treatment-related antagonistic occasions of any grade in better than 15% of sufferers have been diarrhea (40.9%), peripheral edema (23.9%) and paronychia (17.0%).
Further late-breaking information to be introduced at ESMO 2022 embrace translational information for BAVENCIO® (avelumab) characterizing genomic biomarkers in peripheral blood from sufferers enrolled within the Phase III JAVELIN Bladder 100 trial [Proffered Paper #LBA74].
Additional key information to be introduced:
- A mini-oral presentation from the first-in-human Phase I research of M1774, the Company’s probably best-in-class potent and selective inhibitor of ataxia telangiectasia and Rad3-related (ATR) exhibiting a good security profile and pharmacologically related publicity, in sufferers with superior strong tumors (DDRiver Solid Tumors 301) [#457MO] exemplifying the Company’s dedication to advancing understanding of DNA Damage Response (DDR) inhibition mechanisms.
- Exploratory analyses from JAVELIN Bladder 100 that look at medical outcomes in long-term responders with superior urothelial carcinoma handled with BAVENCIO first-line upkeep for ≥12 months [#1760P]. Long-term follow-up information introduced earlier this 12 months bolstered the good thing about BAVENCIO plus greatest supportive care (BSC) within the first-line upkeep setting, with a continued enchancment in OS versus BSC alone for sufferers with domestically superior or metastatic urothelial carcinoma whose tumors had not progressed on a platinum-based chemotherapy.1
- Results from cohorts A and C within the Phase II VISION trial demonstrated strong and sturdy efficacy in treatment-naïve and beforehand handled sufferers with metastatic NSCLC with METex 14-skipping. In beforehand handled sufferers, efficacy was noticed no matter prior therapies together with IO and/or platinum-based CT [#985P].
Other company-sponsored occasions at ESMO 2022 embrace:
Medical Symposia:
- From Complex to Simple: The Journey to Strategic Sequencing within the Management of mCRC (Friday, September 9, 6:00–7:30 PM CEST, 7.3Q Quimper Auditorium, Hall 7, Level 7.3)
- New Approaches to Optimize Treatment Outcomes in Advanced Urothelial Carcinoma (Saturday, September 10, 1:00-2:30 PM CEST, 7.3.U Urval Auditorium, Hall 7, Level 7.3)
- Evolution of SCCHN Treatment (Sunday, September 11, 6:30-8:00 PM CEST, 7.3.0 Orleans Auditorium, Hall 7, Level 7.3).
Continuing Medical Education (CME):
- Navigating Treatment Decisions in Advanced NSCLC: Update on Molecular Testing and New Targeted Treatment Options (Friday, September 9, 10:15-11:45 AM CEST, Quimper Auditorium, Hall 7, Level 7.3)
Select displays (all occasions CEST):
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Title
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Lead Author
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Abstract
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Session Title/Date/Time
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PIPELINE
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5-year total survival (OS) in sufferers with domestically superior squamous cell carcinoma of the top and neck (LA SCCHN) handled with xevinapant+chemoradiotherapy (CRT) vs placebo+CRT in a randomized, section 2 research
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J Bourhis
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LBA33
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Mini Oral Session: Head and Neck Cancer
Saturday, 10 September
10:55 AM
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A First-in-Human Phase I Study of ATR Inhibitor M1774 in Patients with Advanced Solid Tumors
(DDRiver Solid Tumors 301)
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TA Yap
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457MO
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Mini Oral Session:
Developmental Therapeutics
Monday, 12 September
4:55 PM
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Phase 1 research of TIGIT inhibitor M6223 as monotherapy or together with bintrafusp alfa (BA) in sufferers (pts) with metastatic/domestically superior strong unresectable tumours
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LL Siu
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750P
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Investigational immunotherapy
Monday, 12 September
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BAVENCIO (avelumab)
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Characterization of genomic biomarkers in peripheral blood (PB) from sufferers (pts) enrolled within the JAVELIN Bladder 100 trial of avelumab first-line (1L) upkeep in superior urothelial carcinoma (aUC)
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T Powles
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LBA74
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Proffered Paper Session 1: GU tumours, non-prostate
Saturday, 10 September
11:10 AM
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Avelumab versus customary second line remedy chemotherapy in metastatic colorectal most cancers (mCRC) sufferers with microsatellite instability (MSI): the SAMCO-PRODIGE 54 randomised section II trial
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J Taïeb
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LBA23
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Proffered Paper Session 1: GI decrease digestive
Sunday, 11 September
11:15 AM
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Avelumab first-line (1L) upkeep for superior urothelial carcinoma (aUC): outcomes from sufferers with ≥12 mos of remedy in JAVELIN Bladder 100
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J Aragon-Ching
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1760P
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Urothelial Cancer
Monday, 12 September
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Preliminary outcomes from AVENANCE, an ongoing, noninterventional real-world, ambispective research of avelumab first-line (1L) upkeep remedy in sufferers (pts) with domestically superior or metastatic urothelial carcinoma (la/mUC)
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P Barthélémy
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1757P
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Urothelial Cancer
Monday, 12 September
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Avelumab added to FOLFIRI plus cetuximab adopted by avelumab upkeep in sufferers with beforehand
untreated RAS wild-type colorectal most cancers–The phase-II FIRE-6 (AIO KRK-0118)
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S Stintzing
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424P
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Colorectal Cancer
Sunday, 11 September
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TEPTMETKO (tepotinib)
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Tepotinib+osimertinib for EGFR-mutant(m) NSCLC after development on first-line (1L) osimertinib due to MET amplification: Initial outcomes from the INSIGHT 2 research
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J Mazieres
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LBA52
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Proffered Paper Session: NSCLC, metastatic
Sunday, 11 September
2:55 PM
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Tepotinib outcomes in accordance to prior therapies in sufferers with METexon14 (METex14) skipping NSCLC
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E Smit
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985P
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NSCLC, metastatic
Monday, 12 September
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ERBITUX (cetuximab)
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Phase III research with FOLFIRI/Cetuximab versus FOLFIRI/Cetuximab adopted by Cetuximab (Cet) alone in first-line remedy of RAS and BRAF wild sort (wt) metastatic colorectal most cancers (mCRC) sufferers: the ERMES Study (NCT02484833)
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A Orlandi
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LBA22
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Proffered Paper Session 1: GI, decrease digestive
Sunday, 11 September
10:25 AM
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About BAVENCIO® (avelumab)
BAVENCIO is a human anti-programmed dying ligand-1 (PD-L1) antibody. BAVENCIO has been proven in preclinical fashions to have interaction each the adaptive and innate immune capabilities. By blocking the interplay of PD-L1 with PD-1 receptors, BAVENCIO has been proven to launch the suppression of the T cell-mediated antitumor immune response in preclinical fashions. In November 2014, Merck and Pfizer introduced a strategic alliance to co-develop and co-commercialize BAVENCIO.
BAVENCIO Approved Indications
The European Commission (EC) has licensed using BAVENCIO as monotherapy for the first-line upkeep remedy of grownup sufferers with domestically superior or metastatic urothelial carcinoma (UC) who’re progression-free following platinum-based chemotherapy. BAVENCIO together with axitinib is indicated for the first-line remedy of grownup sufferers with superior renal cell carcinoma (RCC). BAVENCIO can also be licensed by the EC for use as a monotherapy for the remedy of grownup sufferers with metastatic Merkel cell carcinoma (MCC).
In the US, BAVENCIO is indicated for the upkeep remedy of sufferers with domestically superior or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy. BAVENCIO can also be indicated for the remedy of sufferers with domestically superior or metastatic UC who’ve illness development throughout or following platinum-containing chemotherapy, or have illness development inside 12 months of neoadjuvant or adjuvant remedy with platinum-containing chemotherapy.
BAVENCIO together with axitinib is indicated within the US for the first-line remedy of sufferers with superior RCC. Additionally, the US Food and Drug Administration (FDA) granted accelerated approval for BAVENCIO for the remedy of adults and pediatric sufferers 12 years and older with metastatic MCC. This indication is authorized underneath accelerated approval based mostly on tumor response charge and length of response. Continued approval for this indication could also be contingent upon verification and outline of medical profit in confirmatory trials.
BAVENCIO is at the moment authorized for at least one indication for sufferers in additional than 50 international locations.
BAVENCIO Safety Profile from the EU Summary of Product Characteristics (SmPC)
The particular warnings and precautions for use for BAVENCIO monotherapy embrace infusion-related reactions, in addition to immune-related antagonistic reactions that embrace pneumonitis and hepatitis (together with deadly instances), colitis, pancreatitis (together with deadly instances), myocarditis (together with deadly instances), endocrinopathies, nephritis and renal dysfunction, and different immune-related antagonistic reactions. The particular warnings and precautions for use for BAVENCIO together with axitinib embrace hepatotoxicity.
The SmPC record of the commonest antagonistic reactions with BAVENCIO monotherapy in sufferers with strong tumors consists of fatigue, nausea, diarrhea, decreased urge for food, constipation, infusion-related reactions, weight decreased and vomiting. The record of most typical antagonistic reactions with BAVENCIO together with axitinib consists of diarrhea, hypertension, fatigue, nausea, dysphonia, decreased urge for food, hypothyroidism, cough, headache, dyspnea, and arthralgia.
About TEPMETKO® (tepotinib)
TEPMETKO is a once-daily oral MET inhibitor that inhibits the oncogenic MET receptor signaling attributable to MET (gene) alterations. Discovered and developed in-house at Merck, TEPMETKO has a extremely selective mechanism of motion, with the potential to enhance outcomes in aggressive tumors which have a poor prognosis and harbor these particular alterations.
TEPMETKO was the primary oral MET inhibitor to obtain a regulatory approval anyplace on this planet for the remedy of superior NSCLC harboring MET gene alterations, with its approval in Japan in March 2020. In February 2021, the US Food and Drug Administration granted accelerated approval to TEPMETKO, making it the primary and solely once-daily oral MET inhibitor authorized for sufferers within the U.S. with metastatic NSCLC with METex14 skipping alterations.
TEPMETKO is offered in quite a lot of international locations. To meet an pressing medical want, TEPMETKO can also be accessible in a pilot zone of China in line with the federal government coverage to drive early entry for revolutionary medicines authorized outdoors of China.
Merck can also be investigating the potential function of tepotinib in treating sufferers with NSCLC and bought resistance due to MET amplification within the Phase II INSIGHT 2 research of tepotinib together with osimertinib in MET amplified, superior or metastatic NSCLC harboring activating EGFR mutations that has progressed following first-line remedy with osimertinib.
TEPMETKOSafety Profile from the EU Summary of Product Characteristics (SmPC)
The particular warnings and precautions for use for TEPMETKO monotherapy embrace Interstitial lung illness (ILD) or ILD-like antagonistic reactions together with pneumonitis, improve of Liver enzymes (ALT and AST), QTc prolongation, and embryo-foetal toxicity.
The most typical antagonistic reactions in ≥ 20% of uncovered to tepotinib at the really useful dose within the goal indication are oedema, primarily peripheral oedema, nausea, hypoalbuminaemia, diarrhoea and improve in creatinine. The most typical severe antagonistic reactions in ≥ 1% of sufferers are peripheral oedema, generalised oedema and ILD.
About ERBITUX® (cetuximab)
ERBITUX is an IgG1 monoclonal antibody concentrating on the epidermal development issue receptor (EGFR). As a monoclonal antibody, the mode of motion of ERBITUX is distinct from customary non-selective chemotherapy remedies in that it particularly targets and binds to the EGFR. This binding inhibits the activation of the receptor and the next signal-transduction pathway, which leads to decreasing each the invasion of regular tissues by tumor cells and the unfold of tumors to new websites. It can also be believed to inhibit the flexibility of tumor cells to restore the harm attributable to chemotherapy and radiotherapy and to inhibit the formation of latest blood vessels inside tumors, which seems to lead to an total suppression of tumor development. Based on in vitro proof, ERBITUX additionally targets cytotoxic immune effector cells in direction of EGFR-expressing tumor cells (antibody-dependent cell-mediated cytotoxicity [ADCC]).
ERBITUX has already obtained market authorization in over 100 international locations worldwide for the remedy of RAS wild-type metastatic colorectal most cancers and for the remedy of squamous cell carcinoma of the top and neck. Merck licensed the suitable to market ERBITUX, a registered trademark of ImClone LLC, outdoors the U.S. and Canada from ImClone LLC, a completely owned subsidiary of Eli Lilly and Company, in 1998.
About Xevinapant
Xevinapant (previously generally known as Debio 1143) is an investigational first-in-class potent oral small-molecule IAP (inhibitor of apoptosis protein) inhibitor for the remedy of LA SCCHN. In preclinical research, xevinapant restored sensitivity to apoptosis in most cancers cells, thereby enhancing the consequences of chemotherapy and radiotherapy. Xevinapant, probably the most clinically superior IAP inhibitor, improved efficacy outcomes together with chemoradiotherapy (CRT), together with three-year progression-free survival and five-year survival, in contrast with placebo plus CRT in a Phase II research in sufferers with unresected domestically superior squamous cell carcinoma of the top and neck (LA SCCHN). In March 2021, Merck gained unique rights from Debiopharm to develop and commercialize xevinapant worldwide. Xevinapant will not be authorized for any use anyplace on this planet.
About Merck
Merck, a number one science and know-how firm, operates throughout life science, healthcare and electronics. More than 60,000 workers work to make a optimistic distinction to tens of millions of individuals’s lives each day by creating extra joyful and sustainable methods to reside. From advancing gene enhancing applied sciences and discovering distinctive methods to deal with probably the most difficult ailments to enabling the intelligence of gadgets – the corporate is in all places. In 2021, Merck generated gross sales of € 19.7 billion in 66 international locations.
Scientific exploration and accountable entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding household stays the bulk proprietor of the publicly listed firm. Merck holds the worldwide rights to the Merck identify and model. The solely exceptions are the United States and Canada, the place the business sectors of Merck function as MilliporeSigma in life science, EMD Serono in healthcare, and EMD Electronics in electronics.
Reference:
1 Powles T, Park SH, Voog E, et al. Avelumab first-line (1L) upkeep for superior urothelial carcinoma (UC): Long-term follow-up outcomes from the JAVELIN Bladder 100 trial. J Clin Oncol 40, 2022 (suppl 6; abstr 487).
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