Pembrolizumab, Merck's Investigational anti PD-1 Therapy, Demonstrates Superior Survival, Progression Free Survival and Overall Response Rate Compared to Ipilimumab, an Anti-CTLA-4 Therapy, in a Phase 3 Study of Patients with Advanced Melanoma

Data from KEYNOTE-006 Study Presented at AACR Annual Meeting and Published in the New England Journal of Medicine

KIRKLAND, QC, April 19, 2015 /CNW Telbec/ - Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced results from the randomized, pivotal Phase 3 study, KEYNOTE-006, in the treatment of unresectable advanced melanoma. In the study, pembrolizumab was statistically superior to ipilimumab for progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). On March 24, 2015, Merck announced that KEYNOTE-006 would be stopped early based on these data. The results will be presented today at the American Association for Cancer Research (AACR) Annual Meeting by Dr. Antoni Ribas of Jonsson Comprehensive Cancer Center, University of California, Los Angeles (abstract # CT101, included in the AACR press program), and were also published today in the New England Journal of Medicine.

 "Improving survival is the ultimate objective in treating patients with cancer. In this important study in advanced melanoma, pembrolizumab was statistically superior to ipilimumab for progression-free survival and overall survival, and also demonstrated a lower frequency of severe adverse events." said Dr. Caroline Robert, head of Dermatology at Gustave Roussy, Villejuif and Paris-Sud University Cancer Campus, Grand Paris and lead author of the New England Journal of Medicine publication.

"Our goal with the pembrolizumab development program is to help improve long-term disease control and survival for people with a wide range of cancers," said Dr. Roger Perlmutter, president, Merck Research Laboratories. "The KEYNOTE-006 study compared two immunotherapies that target distinct immune checkpoint pathways, PD-1 and CTLA-4. In this study, our investigational anti-PD-1 antibody, pembrolizumab, improved overall survival by more than 30 percent compared to ipilimumab, an anti-CTLA-4 antibody, in the treatment of advanced melanoma. We look forward to filing these data with health authorities around the world."

"Metastatic melanoma is a devastating disease with a very poor prognosis and historically, therapeutic options have been limited," explained Dr. Teresa Petrella, Head of the Melanoma Disease Site Group at the Odette Cancer Centre, Sunnybrook Health Sciences Centre. "However, new agents and treatment strategies are changing the landscape of the management of melanoma. The rapidly evolving field of immuno-oncology is finally bringing new hope to cancer patients in Canada."  She adds, "Many Canadian melanoma patients participated in the KEYNOTE-006 trial. This is an exciting time in melanoma, and new therapies that have now shown an improvement in overall survival represent a potential new treatment option in a population with a high unmet need."

KEYNOTE-006 Results in the Front-Line Treatment of Advanced Melanoma  

KEYNOTE-006 is a global, open-label, randomized, pivotal, Phase 3 study (ClinicalTrials.gov, NCT01866319) of 834 patients from 16 countries with unresectable stage III or IV advanced melanoma with no more than one prior systemic therapy. Patients received pembrolizumab 10 mg/kg every two weeks (n=279), pembrolizumab 10 mg/kg every three weeks (n=277), or four cycles of ipilimumab 3 mg/kg every three weeks (n=278). The primary endpoints were PFS and OS; secondary endpoints were ORR, duration of response, and safety. Tumour response was assessed at week 12, then every six weeks thereafter by independent central review per RECIST 1.1. This first presentation of data from KEYNOTE-006 is based on interim analyses conducted for PFS with a data cut-off of September 3, 2014 (median follow-up, 7.9 months) and for OS with a data cut off of March 3, 2015 (median follow-up, 13.8 months).

Data Showed Pembrolizumab was Statistically Superior to Ipilimumab for PFS, OS and ORR

The median PFS for pembrolizumab was 5.5 months (2-week group) and 4.1 months (3-week group) compared to 2.8 months for ipilimumab (HR 0.58, P<0.00001 for the pembrolizumab groups vs. ipilimumab, 95% CI, 0.46-0.72 for 2-week group and 0.47-0.72 for 3-week group, respectively). The estimated 6-month PFS rates for the pembrolizumab and ipilimumab arms were 47.3 percent, 46.4 percent and 26.5 percent, respectively. One-year OS for pembrolizumab was 74.1 percent (2-week group) and 68.4 percent (3-week group) compared to 58.2 percent for ipilimumab (HR 0.63 [95% CI, 0.47-0.83, P=0.00052] for the 2-week group and HR 0.69 [95% CI, 0.52-0.90, P=0.00358] for the 3-week group). At the time of analysis, median overall survival was not reached in any treatment group.

ORR for pembrolizumab was 33.7 percent (2-week group) and 32.9 percent (3-week group) compared to 11.9 percent for ipilimumab (P=0.00013 for 2-week group; P=0.00002 for 3-week group); complete response rates were 5.0 percent, 6.1 percent, and 1.4 percent, respectively. Responses were ongoing in 89.4 percent (2-week group) and 96.7 percent (3-week group) of pembrolizumab-treated patients and in 87.9 percent of ipilimumab-treated patients. Median duration of response was not reached for pembrolizumab 3-week group (42+ to 246+) and ipilimumab (33+ to 239+).

The efficacy and safety profiles were similar between the two pembrolizumab schedules evaluated in the study. Two previous studies, KEYNOTE-001 and KEYNOTE-002, demonstrated that the efficacy and safety were similar among the pembrolizumab doses and schedules evaluated; 10 mg/kg every two weeks, 10 mg/kg every three weeks, and 2 mg/kg every three weeks. 

Safety Findings from KEYNOTE-006

The safety profile of pembrolizumab in this study was generally consistent with previously reported safety data. The most common treatment-related adverse events of any grade occurring in the pembrolizumab groups were fatigue, diarrhea, rash, and pruritus. For ipilimumab, the most frequent treatment-related adverse events were pruritus, diarrhea, fatigue, and rash. Grade 3 to 4 treatment-related adverse events occurred in 13.3 percent (2-week group) and 10.1 percent (3-week group) of patients treated with pembrolizumab and in 19.9 percent for ipilimumab. Discontinuation due to treatment-related adverse events was less frequent with pembrolizumab (2-week group and 3-week group) than with ipilimumab (4.0%, 6.9%, and 9.4%, respectively). One death in the ipilimumab group was attributed to study treatment.

Treatment-related adverse events of an autoimmune or immune-related nature most frequently observed with pembrolizumab (2-week group and 3-week group) were hypothyroidism (10.1% and 8.7%) and hyperthyroidism (6.5% and 3.2%). With ipilimumab, colitis occurred in 8.2 percent of patients. Grade 3 to 4 inflammatory or immune-mediated treatment events reported in more than 1 percent of pembrolizumab-treated patients (2-week group and 3-week group) were colitis (1.4% and 2.5%) and hepatitis (1.1% and 1.8%), and in ipilimumab-treated patients were colitis (7.0%) and hypophysitis (1.6%).

About Pembrolizumab

Pembrolizumab 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, pembrolizumab releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumour immune response.

Merck is advancing a broad and fast-growing clinical development program for pembrolizumab with more than 85 clinical trials – across more than 30 tumour types and over 14,000 patients – both as a monotherapy and in combination with other therapies.

About Melanoma

Melanoma, the most serious form of skin cancer¹, 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 Canada, in 2014, it was estimated that 6,500 Canadians would be diagnosed with melanoma, while 1,050 Canadians would die from melanoma².

The five-year survival rates for advanced or metastatic melanoma (Stage IV) are estimated to be 15 to 20 percent.

Our Focus on Cancer

Our goal is to translate breakthrough science into biomedical innovations to help people with cancer worldwide. For Merck Oncology, helping people fight cancer is our passion, supporting accessibility to our cancer medicines is our commitment, and pursuing research in immuno-oncology is our focus to potentially bring new hope to people with cancer. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside Canada and the United States. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information about our operations in Canada, visit www.merck.ca.

Forward-Looking Statement

This news release includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck's 2014 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (www.sec.gov).

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¹ Medline Plus. (May 2012). Melanoma. Retrieved on April 18, 2015 from http://www.nlm.nih.gov/medlineplus/ency/article/000850.htm

² Canadian Cancer Society.  Melanoma.  Retrieved on April 18, 2015 from http://www.cancer.ca/en/cancer-information/cancer-type/skin-melanoma/statistics/?region=sk

SOURCE Merck

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