Merck Receives Breakthrough Therapy Designation from U.S.FDA for KEYTRUDA(R) (pembrolizumab) in Advanced Colorectal Cancer

Merck (NYSE: MRK), known as MSD outside the United States and Canada, todayannounced that the U.S. Food and Drug Administration (FDA) has grantedBreakthrough Therapy Designation to KEYTRUDA(R) (pembrolizumab), thecompany's anti-PD-1 therapy, for the treatment of patients withmicrosatellite instability high (MSI-H) metastatic colorectal cancer. Thisis the third Breakthrough Therapy Designation granted for KEYTRUDA. "We are committed to understanding the full potential of KEYTRUDA to helppatients with a broad range of difficult-to-treat cancers," said Dr. RogerM. Perlmutter, president, Merck Research Laboratories. "The datainvestigating the use of KEYTRUDA in patients with advanced colorectalcancer whose tumors have substantial evidence of mismatch DNA repair defectshave been encouraging, and we appreciate the opportunity that this FDABreakthrough Therapy Designation provides us to accelerate our effort tobring KEYTRUDA to these patients." The FDA's Breakthrough Therapy Designation is intended to expedite thedevelopment and review of a candidate that is planned for use, alone or incombination, to treat a serious or life-threatening disease or conditionwhen preliminary clinical evidence indicates that the drug may demonstratesubstantial improvement over existing therapies on one or more clinicallysignificant endpoints. KEYTRUDA was previously granted breakthrough statusfor advanced melanoma and advanced non-small cell lung cancer (NSCLC). The Breakthrough Therapy Designation in advanced colorectal cancer is basedon data from a Phase 2 study evaluating the activity of KEYTRUDA in cancerswith microsatellite instability, a well-established feature seen in cellswith certain types of DNA repair defects. Findings from the study, led byresearchers from Johns Hopkins Kimmel Cancer Center, were presented at the2015 American Society of Clinical Oncology (ASCO) annual meeting and werepublished simultaneously in the New England Journal of Medicine. Testing tumors for microsatellite instability can identify patients withdefective DNA mismatch repair (MMR) systems. DNA MMR is a process thatpermits cells to recognize and repair genetic mismatches generated duringDNA replication. A defective MMR system allows mismatch mutations topersist. The average tumor has dozens of mutations; however tumors with DNAMMR deficiency may harbor thousands, especially in regions of repetitive DNAknown as microsatellites. Tumors that are found to have mutations in selectmicrosatellite sequences, called microsatellite instability (MSI), areconsidered DNA MMR-deficient. These tumors are referred to as being "MSIhigh." Overall, DNA MMR-deficiency is present in approximately 15-20 percentin Stage II disease, 10 percent in Stage III disease and approximately 5percent or less in Stage IV disease. In colorectal cancers, MMR-deficiencyis seen in approximately 15-20 percent of non-hereditary colorectal cancersand in most hereditary colorectal cancers associated with Lynch Syndrome. Merck is conducting a Phase 2 registration study (KEYNOTE-164) to evaluatethe efficacy and safety of KEYTRUDA based on microsatellite instabilitystatus in patients with previously treated advanced colorectal cancers, andis also planning a Phase 3 study (KEYNOTE-177) in a treatment naïvepatient population. The KEYTRUDA clinical development program includes patients with more than30 tumor types in more than 160 clinical trials, including more than 80trials that combine KEYTRUDA with other cancer treatments.Registration-enabling trials of KEYTRUDA are currently enrolling patients inmelanoma, 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 othercancers.