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Merck Phase III Trial of Anti-PD-1 Drug (Keytruda) Meets Co-Primary Endpoints As First-Line Treatment for Advanced Melanoma and Trial Will Be Stopped Early; Keytruda Found Superior to Ipilimumab

Merck (NYSE:MRK), known as MSD outside the United States and Canada, announced on March 24, 2015 that the randomized, pivotal Phase 3 study (KEYNOTE-006) investigating KEYTRUDA® (pembrolizumab) compared to ipilimumab in the first-line treatment of patients with advanced melanoma has met its two primary endpoints of progression-free survival and overall survival. The trial will be stopped early based on the recommendation of the study’s independent Data Monitoring Committee. In the KEYNOTE-006 trial, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in overall survival and progression-free survival compared to ipilimumab. The safety profile of KEYTRUDA in this trial was similar to the safety profile previously reported in advanced melanoma. KEYTRUDA is the first anti-PD-1 therapy to demonstrate a survival advantage compared to the standard of care for the first-line treatment of advanced melanoma. These data will be presented in the opening plenary session at the American Association of Cancer Research (AACR) Annual Meeting in Philadelphia, Pennsylvania, April 18-22, 2015. "Evidence from our clinical program for KEYTRUDA will help to define the appropriate treatment of advanced melanoma," said Dr. Roger Perlmutter, President, Merck Research Laboratories. "We greatly appreciate the efforts of our investigators and their patients in this important study, and we look forward to the presentation of overall survival data from KEYNOTE-006 at the AACR annual meeting." KEYNOTE-006 was a global, open-label, randomized, pivotal, Phase 3 study (ClinicalTrials.gov, NCT01866319) evaluating KEYTRUDA compared to ipilimumab in patients with unresectable stage III or IV advanced melanoma with no more than one prior systemic therapy. The study randomized 834 patients to receive KEYTRUDA 10 mg/kg every three weeks, KEYTRUDA 10 mg/kg every two weeks, or four cycles of ipilimumab 3 mg/kg every three weeks. The co-primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints were overall response rate (ORR), duration of response, and safety, with an exploratory analysis for health-related quality of life (QoL). Tumor response was assessed at week 12, then every 6 weeks thereafter per RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) by independent, central, blinded radiographic review and investigator-assessed, immune-related response criteria.

ABOUT KEYTRUDA (PEMBROLIZUMAB)

KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody that blocks the interaction between PD-1 (programmed death receptor-1) (http://en.wikipedia.org/wiki/Programmed_cell_death_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 70 clinical trials – across more than 30 tumor types and over 8,000 patients – both as a monotherapy and in combination with other therapies.

ABOUT MELANOMA

Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The incidence of melanoma has been increasing over the past four decades –approximately 232,130 new cases were diagnosed worldwide in 2012. In the U.S., melanoma is one of the most common types of cancer diagnosed and is responsible for the vast majority of skin cancer deaths. In 2014, an estimated 76,100 people were expected to be diagnosed and an estimated 9,710 people were expected to die of the disease in the U.S. alone. The five-year survival rates for advanced or metastatic melanoma (Stage IV) are estimated to be 15 to 20 percent.

ADDITIONAL INFORMATION

Additional information on KEYTRUDA and, particularly, on important related safety information, can be found in the complete press release, for which a link is provided below.

Note that links to popular press stories on this important breaking development are also provided below.

Links to previous BioQuick articles on the development of this drug are also provided.

[Merck press release] [BioQuick news article February 13, 2015] [BioQuick news article September 5, 2014] [Wall Street Journal article] [Fox News article] [Fortune article] [Investor's Business Daily article] [Medscape article] [Reuters article]