Publicado 17/05/2018 13:25:00CET
Presentation Date / Time Title Lead Author Abstract # (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 Apostolia PI3K/AKT/mTOR Maria Mon, Jun 04, (PAM) pathway Tsimberidou, 8:00 AM - 11:30 abnormalities. MD, PhD 2584 AM Hall A
Presentation Date / Time Title Lead Author Abstract # (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: Baukelien Van Mon, Jun 04, Dose-escalation Triest, MD, 3:00 PM - 4:15 results. PhD 2518 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 Geraldine Mon, Jun 04, in patients with Helen O'Sullivan 8:00 AM - advanced solid tumors. Coyne, MD,PhD 2549 11:30 AM Hall A Publication Safety and tolerability of intravenous M6620 (VX-970) administered with gemcitabine in Plummer R, subjects with advanced Cook N, Mon, Jun 04, non-small cell lung Arkenau H-T, 8:00 AM - cancer (NSCLC) et al. e21048 11:30 AM Hall A
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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(R)) 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(R) (cetuximab)
Erbitux(R) 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.
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.
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.
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.
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.
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.