Date: 2015-11-02
Type of information: Granting of the Breakthrough Therapy status
Product name: Keytruda®
Compound: pembrolizumab (MK-3475)
Therapeutic area: Cancer - Oncology
Action mechanism:
- monoclonal antibody/immune checkpoint inhibitor. Keytruda® (pembrolizumab - MK-3475) is a monoclonal anti-PD-1 antibody designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system. In April 2013, MK-3475 has received a Breakthrough Therapy designation for advanced melanoma from the FDA. In October 2014, the FDA has gralso anted Breakthrough Therapy Designation to Keytruda® for the treatment of patients with Epidermal Growth Factor Receptor (EGFR) mutation-negative, and Anaplastic Lymphoma Kinase (ALK) rearrangement-negative NSCLC whose disease has progressed on or following platinum-based chemotherapy. Keytruda® is the first approved drug that blocks the PD-1 cellular pathway. The Keytruda® clinical development program includes patients with more than 30 tumor types in more than 160 clinical trials, including more than 80 trials that combine Keytruda® with other cancer treatments. Registration-enabling trials of Keytruda® are currently enrolling patients in melanoma, NSCLC, head and neck cancer, bladder cancer, gastric cancer, colorectal cancer, esophageal cancer, breast cancer, Hodgkin lymphoma, multiple myeloma and other tumors, with further trials in planning for other cancers.
Company: Merck&Co (USA - NJ)
Disease: advanced colorectal cancer
Latest news:
- • On November 2, 2015, Merck&Co announced that the 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 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.
- Testing tumors for microsatellite instability can identify patients with defective DNA mismatch repair (MMR) systems. DNA MMR is a process that permits cells to recognize and repair genetic mismatches generated during DNA replication. A defective MMR system allows mismatch mutations to persist. The average tumor has dozens of mutations; however tumors with DNA MMR deficiency may harbor thousands, especially in regions of repetitive DNA known as microsatellites. Tumors that are found to have mutations in select microsatellite sequences, called microsatellite instability (MSI), are considered DNA MMR-deficient. These tumors are referred to as being “MSI high.” Overall, DNA MMR-deficiency is present in approximately 15-20 percent in Stage II disease, 10 percent in Stage III disease and approximately 5 percent or less in Stage IV disease. In colorectal cancers, MMR-deficiency is seen in approximately 15-20 percent of non-hereditary colorectal cancers and in most hereditary colorectal cancers associated with Lynch Syndrome.
- Merck&Co is conducting a Phase 2 registration study (KEYNOTE-164 - NCT02460198) to evaluate the efficacy and safety of Keytruda® based on microsatellite instability status in patients with previously treated advanced colorectal cancers, and is also planning a Phase 3 study (KEYNOTE-177 - NCT02563002) in a treatment naïve patient population.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
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Favourable opinion USA:
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Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
