Merck Data at ASCO 2019 Showcase Multiple Innovative Molecules with Potential to Impact Unmet Needs in Cancer Care (2)

Publicado 16/05/2019 0:19:08CET

Title Lead Author Abstract # Presentation Location Date / Time ( CDT ) BAVENCIO(R) (avelumab) Oral Session Biomarker analyses from T.K. Choueiri 101 Sat, Jun 1, 8:00 Hall D1 JAVELIN Renal 101: AM - 9:30 AM avelumab + axitinib (8:12 AM - 8:24 (A+Ax) vs sunitinib (S) AM lecture time) in advanced renal cell carcinoma (aRCC) --- --- Poster Sessions --- 5-factor prognostic G. Sonpavde 4552 Mon, Jun 3, 1:15 Hall A model for survival of PM - 4:15 PM patients with metastatic urothelial carcinoma receiving 3 different post-platinum PD-L1 inhibitors --- --- First-line avelumab + M. Kudo 4072 Mon, Jun 3, 8:00 Hall A axitinib in patients with AM - 11:00 AM advanced hepatocellular carcinoma: results from a phase 1b trial (VEGF Liver 100) --- --- Integrative molecular S. Georges 9569 Mon, Jun 3, 1:15 Hall A analysis of metastatic PM - 4:15 PM Merkel cell carcinoma to identify predictive biomarkers of response to avelumab --- --- Bintrafusp Alfa --- Poster Session --- Randomized open-label L. Paz-Ares TPS9114 Sun, Jun 2, 8:00 Hall A study of M7824 vs AM - 11:00 AM pembrolizumab as first- line (1L) treatment in patients with PD-L1 expressing advanced non-small cell lung cancer (NSCLC) --- --- Discovery --- Poster Session --- Understanding P.K. Shah 2567 Sat, Jun 1, 8:00 Hall A contribution and AM - 11:00 AM independence of multiple biomarkers for predicting response to atezolizumab --- --- ERBITUX(R) (cetuximab) --- Poster Session --- Retrospective Analysis of A. Sobrero 3580 Mon, Jun 3, 8:00 Hall A Overall Survival (OS) by AM - 11:00 AM Subsequent Therapy in Patients With RAS-Wild- type (wt) Metastatic Colorectal Cancer (mCRC) Receiving Cetuximab +/- Irinotecan --- --- Tepotinib --- Oral Session --- Phase II study of P.K. Paik 9005 Mon, Jun 3, 8:00 AM - Hall B1 tepotinib in 11:00 AM (9:24 NSCLC patients with AM - 9:36 AM METex14 mutations lecture time) --- ---

About Tepotinib

Tepotinib, discovered in-house at Merck, is an investigational oral MET inhibitor that is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, including both MET exon 14 skipping mutations and MET amplifications, or MET protein overexpression. It has been designed to have a highly selective mechanism of action, with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.

Tepotinib is currently being investigated in NSCLC and Merck is actively assessing the potential of investigating tepotinib in combination with novel therapies and other tumor indications.

About Bintrafusp Alfa (M7824)

Bintrafusp alfa is an investigational bifunctional immunotherapy that is designed to combine a TGF- trap with the anti-PD-L1 mechanism in one fusion protein. Bintrafusp alfa is designed to combine co-localized blocking of the two immuno-suppressive pathways - targeting both pathways aims to control tumor growth by potentially restoring and enhancing anti-tumor responses. Bintrafusp alfa is currently in Phase I studies for solid tumors, as well as a randomized Phase II trial to investigate bintrafusp alfa 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 bintrafusp alfa versus pembrolizumab as a monotherapy treatment.

To date, nearly 700 patients have been treated with bintrafusp alfa across more than 10 tumor types in Phase I studies. Encouraging data from the ongoing Phase I studies indicates bintrafusp alfa's potential safety and clinical anti-tumor activity across multiple types of difficult-to-treat cancers, including advanced NSCLC, human papillomavirus-associated cancers, biliary tract cancer and gastric cancer. In addition, in pre-clinical studies bintrafusp alfa demonstrated superior anti-tumor activity, compared with anti-PD-L1 alone or with anti-PD-L1 and TGF- trap when co-administered. In total, eight high-priority immuno-oncology clinical development studies are ongoing or expected to commence in 2019, including studies in non-small cell lung and biliary tract cancers.

About BAVENCIO(® )(avelumab)

BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO 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, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.(1-3) BAVENCIO has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.(3-5) In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and about 10,000 patients evaluated across more than 15 different tumor types. These tumor types include RCC, gastric/gastro-esophageal junction cancer, head and neck cancer, Merkel cell carcinoma, non-small cell lung cancer, and urothelial carcinoma.

BAVENCIO approved Indications

In September 2017, the European Commission granted conditional marketing authorization for BAVENCIO as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC). BAVENCIO is currently approved for patients with MCC in more than 45 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

BAVENCIO(®) (avelumab) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

In the US, the FDA granted accelerated approval for 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.

BAVENCIO(®) Safety Profile from the EU Summary of Product Characteristics (SmPC)

The special warnings and precautions for use for BAVENCIO include infusion-related reactions and immune-related adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, and other adverse reactions).

The SmPC list of the most common adverse reactions in patients with solid tumors includes fatigue, nausea, diarrhea, decreased appetite, constipation, infusion-related reactions, and weight loss and vomiting.

Axitinib Important Safety Information from the US FDA Approved Label

In the study of advanced RCC after failure of one prior systemic therapy, the warnings and precautions for axitinib include hypertension, including hypertensive crisis, arterial and venous thrombotic events, hemorrhagic events, cardiac failure, gastrointestinal perforation and fistula, hypothyroidism, wound healing complications, reversible posterior leukoencephalopathy syndrome (RPLS), proteinuria, liver enzyme elevation, hepatic impairment, and fetal harm during pregnancy.

Common adverse events (reported in at least 20% of patients) in patients receiving axitinib were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, weight decreased, vomiting, asthenia, and constipation.

About ERBITUX(®) (cetuximab)

Erbitux(®) is an 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. Based on in vitro evidence, Erbitux(®) also targets cytotoxic immune effector cells towards EGFR-expressing tumor cells (antibody-dependent cell-mediated cytotoxicity [ADCC]).

Very commonly reported side effects with Erbitux(®) include acne-like skin rash, mild to moderate infusion-related reactions and hypomagnesemia.

Erbitux(®) has already obtained market authorization in 114 countries worldwide for the treatment of RAS wild-type metastatic colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck. 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.

References

1. Dolan DE, et al. Cancer Control 2014;21:231-7. 2. Dahan R, et al. Cancer Cell 2015;28:285-95. 3. Boyerinas B, et al. Cancer Immunol Res 2015;3:1148-57. 4. Kohrt HE, et al. Immunotherapy 2012;4:511-27. 5. Hamilton G, et al. Expert Opin Biol Ther 2017;17:515-23.

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