FDA Approves Expanded Indication of KEYTRUDA in Melanoma

Merck announced that the U.S. Food and Drug Administration (FDA) has approved an expanded indication for KEYTRUDA^® (pembrolizumab), the company’s anti-PD-1 (programmed death receptor-1) therapy, to include the first-line treatment of patients with unresectable or metastatic melanoma. This approval marks the second FDA-approved indication in advanced melanoma for KEYTRUDA, which is now the first anti-PD-1 therapy approved for previously untreated advanced melanoma patients regardless of BRAF status. The FDA-approved dose of KEYTRUDA is 2 mg/kg every three weeks

KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

For details enter clinical trial of KEYTRUDA  visit here

Amgen to Present IMLYGIC Data

Amgen announced that the Company will present eight IMLYGIC (talimogene laherparepvec) abstracts, including data from the Phase 3 trial and new data from its Phase 1b combination trial with Merck's anti-PD-1 therapy, at the 12^th International Congress of the Society for Melanoma Research (SMR), to be held on Nov. 18-21 in San Francisco. 

The Phase 1b data on IMLYGIC in combination with an investigational use of Merck's anti-PD-1 therapy, KEYTRUDA^® (pembrolizumab), in patients with unresectable metastatic melanoma has been accepted as a late-breaking abstract.

IMLYGIC is a genetically modified herpes simplex type 1 virus that is injected directly into tumors. IMLYGIC replicates inside tumor cells and produces GM-CSF, an immunostimulatory protein. IMLYGIC then causes the cell to rupture and die in a process called lysis. The rupture of the cancer cells causes the release of tumor-derived antigens, which together with virally derived GM-CSF may help to promote an anti-tumor immune response. However, the exact mechanism of action is unknown.

 

IMLYGIC is the first oncolytic viral therapy approved by the FDA based on therapeutic benefit demonstrated in a pivotal study. IMLYGIC is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. IMLYGIC has not been shown to improve overall survival or have an effect on visceral metastases.

Merck Receives Breakthrough Therapy Designation from USFDA

Merck announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to KEYTRUDA^® (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of patients with microsatellite instability high (MSI-H) metastatic colorectal cancer. This is the third Breakthrough Therapy Designation granted for KEYTRUDA. 

The FDA’s Breakthrough Therapy Designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. KEYTRUDA was previously granted breakthrough status for advanced melanoma and advanced non-small cell lung cancer (NSCLC). 

The Breakthrough Therapy Designation in advanced colorectal cancer is based on data from a Phase 2 study evaluating the activity of KEYTRUDA in cancers with microsatellite instability, a well-established feature seen in cells with certain types of DNA repair defects. Findings from the study, led by researchers from Johns Hopkins Kimmel Cancer Center, were presented at the 2015 American Society of Clinical Oncology (ASCO) annual meeting and were published simultaneously in the New England Journal of Medicine.

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells. 

New Findings Show Anti-Tumor Activity of KEYTRUDA

Merck announced the first-time presentation of findings investigating the use of KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, as a monotherapy in patients with advanced unresectable nasopharyngeal carcinoma (NPC) – a type of head and neck cancer – whose tumors express PD-L1 (≥1% of cells in tumor nests or PD-L1+ bands in stroma). Data were from a Phase 1b study (KEYNOTE-028) and showed an overall response rate (ORR) (confirmed and unconfirmed) of 22.2 percent (95% CI, 8.6-42.3) in evaluable patients (n=27) who were treated with KEYTRUDA. 

Merck has initiated a comprehensive clinical development program evaluating KEYTRUDA in head and neck cancer across multiple lines of therapy as monotherapy and in combination with chemotherapy as well as other agents. In KEYNOTE-028, KEYTRUDA is being evaluated in patients with advanced unresectable NPC that is not responding to current therapy or for which current therapy is not appropriate. This is the second study to show early activity of KEYTRUDA in patients with head and neck cancer and the first study of an anti-PD-1 therapy to demonstrate clinical activity in patients with recurrent or metastatic NPC.

PD-L1, also called programmed death-ligand 1, is a protein expressed on many types of cells, including some cancer cells. Under normal conditions, the interaction of PD-L1 with another protein, called programmed death receptor-1 (PD-1), serves as an important immune system checkpoint, keeping the immune system in balance and preventing the body from attacking its own cells when inflammation or an infection is present. When cancerous tumors express PD-L1, however, they are able to escape detection and destruction by cytotoxic T-cells – a type of cancer-killing immune cell – allowing the tumor to survive and grow. Tumor PD-L1 expression has been observed at varying levels across many tumor types, including breast, lung, bladder cancer, and nasopharyngeal carcinoma. High levels of PD-L1 expression, called overexpression, are under investigation for potential use as a way to help identify patients with an enhanced likelihood to respond to certain immune-based treatment approaches.

Merck and MD Anderson Cancer Center in Collaboration

Merck and The University of Texas MD Anderson Cancer Center today announced that they have entered into a strategic clinical research collaboration to evaluate Merck’s anti-PD-1 therapy, KEYTRUDA^® (pembrolizumab), in combination with other treatments, such as chemotherapy, radiation therapy and/or novel antitumor medicines. 

Under the terms of the agreement, collaborative studies will be conducted in the following tumor types: gastroesophageal adenocarcinoma, pancreatic adenocarcinoma, and hepatocellular carcinoma -- over the three year period of the collaboration. The first studies are scheduled to start enrolling later this year. 

The agreement aims to define what combination modalities will work best with KEYTRUDA in these types of tumors by exploring promising new alternatives. The studies will be conducted in parallel, in order to determine optimal regimens in the most efficient manner possible. All studies will feature state-of-the-art monitoring protocols and built-in flexibility to take advantage of the very latest information available. 

MD Anderson is a world-recognized academic research institution that has consistently led the charge in researching breakthrough cancer therapies, and was a key contributor to early investigations exploring the use of KEYTRUDA in the treatment of multiple tumor types. Past research collaborations with Merck and MD Anderson were pivotal in achieving the FDA approval of KEYTRUDA as a treatment for unresectable or metastatic melanoma.  

KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, KEYTRUDA releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. 

KEYTRUDA is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. 

Merck is advancing a broad and fast-growing clinical development program for KEYTRUDA with more than 100 clinical trials – across more than 30 tumor types and enrolling more than 16,000 patients – both as a monotherapy and in combination with other therapies.