Merck Announces Positive Data Investigating the Use of Pembrolizumab in Patients with Advanced Triple-Negative Breast Cancer at 2014 San Antonio Breast Cancer Symposium

18.5 Percent Overall Response Rate Observed in Pembrolizumab-Treated Patients with this Aggressive Form of Breast Cancer

Phase 2 Study Planned for the First Half of 2015 (KEYNOTE-086)

KIRKLAND, QC, Dec. 10, 2014 /CNW Telbec/ - Merck, known as MSD outside of Canada and the United States, announced today early pembrolizumab study findings demonstrating an overall response rate of 18.5 percent (n=5/27) in patients with PD-L1 positive, advanced triple-negative breast cancer – one of the most aggressive forms of breast cancer.  Pembrolizumab is the Merck investigational anti-PD-1 therapy.

At the time of analysis, the median duration of response had not been reached with three of five responders on therapy for 11 months or more (range, 15 to 40+ weeks). These early findings, from the ongoing Phase 1b KEYNOTE-012 study, were shared today for the first time as part of the official press program at the 2014 San Antonio Breast Cancer Symposium (SABCS) (ABSTRACT #S1-09) and will be presented in an oral session at 10:45 a.m. CST by Dr. Rita Nanda, the University of Chicago.

"Metastatic, triple-negative breast cancer is an aggressive and often difficult to treat disease," said Dr. Rita Nanda, associate director, Breast Medical Oncology, the University of Chicago and principal investigator for the pembrolizumab triple-negative breast cancer Phase 1b study cohort. "The results presented at this year's SABCS, while early, show encouraging anti-tumor activity in these patients, most of whom had received multiple prior chemotherapies."

 "This year, Merck has significantly advanced our immuno-oncology development program and new data for pembrolizumab have been presented in seven different cancers, including these first findings in triple-negative breast cancer," said Dr. Alise Reicin, vice president, Global Clinical Development, Oncology, Merck Research Laboratories. "These early data with pembrolizumab show responses in patients with one of the most aggressive forms of breast cancer and further our understanding of the PD-1 pathway's role in this disease. Our Phase 2 study planned for the first half of 2015 will be an important next step for our breast cancer clinical program."

Early Findings Evaluating pembrolizumab in Advanced Triple-Negative Breast Cancer

Data presented were from a cohort of the ongoing Phase 1b KEYNOTE-012 study which evaluated pembrolizumab monotherapy at 10 mg/kg every two weeks in patients with advanced triple-negative breast cancer whose tumors were determined to be positive for PD-L1 expression (n=32). As measured by Merck's proprietary PD-L1 immunohistochemistry (IHC) clinical trial assay, tumors were considered to be PD-L1 positive if staining was present in the stroma or in greater than or equal to one percent of tumor cells. In the study, 58 percent of patients screened had tumors determined to be positive for PD-L1 expression. Most patients enrolled in this study had received two or more prior chemotherapies for metastatic disease and 87.5 percent had received prior neo-adjuvant or adjuvant therapy.

Antitumor Activity with Pembrolizumab by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Central Review*

	Patients Evaluable for Response (n=27)^a
Overall Response Rate (ORR), n (%)	5 (18.5%)
Best Overall Response, n (%)
- Complete Response^b	1 (3.7%)
- Partial Response^b	4 (14.8%)
- Stable Disease	7 (25.9%)
- Progressive Disease	12 (44.4%)
- No Assessment^c	3 (11.1%)

*Analysis cut-off as of: November 10, 2014.

^aIncludes patients with measurable disease at baseline who received ≥1 pembrolizumab dose and who had ≥1 post-baseline scan or discontinued therapy before the first scan due to progressive disease or a treatment-related AE. Five patients were excluded because they did not have any assessments per central review (n=2) or because they did not have measurable disease per central review at baseline (n=3).

^bConfirmed responses only.

^c"No assessment" signifies patients who discontinued therapy before the first post-baseline scan due to progressive disease or a treatment-related AE.

The median time to response was 18 weeks (range, 7-32 weeks). In the study, 33 percent of patients with pembrolizumab achieved tumor shrinkage.  At six months, the progression-free survival rate with pembrolizumab was 23.3 percent.

Adverse events were consistent with previously reported safety data for pembrolizumab. The most common treatment-related adverse events (occurring in greater than or equal to five percent of patients) included arthralgia (n=6), fatigue (n=6), myalgia (n=5), nausea (n=5), ALT increased (n=2), AST increased (n=2), diarrhea (n=2), erythema (n=2) and headache (n=2). Grade 3-5 treatment-related adverse events occurred in a total of five patients and included anemia, disseminated intravascular coagulation (DIC), headache, meningitis aseptic, decreased blood fibrinogen, and pyrexia. Two patients discontinued pembrolizumab due to adverse events. One treatment-related death was reported in a patient with rapidly progressive disease and was due to DIC with thrombocytopenia and decreased blood fibrinogen.

About the KEYNOTE-012 Study

KEYNOTE-012 is an ongoing multi-center, non-randomized Phase 1b trial evaluating the safety, tolerability, and anti-tumor activity of pembrolizumab monotherapy in patients with advanced triple-negative breast cancer, advanced head and neck cancer, advanced urothelial (bladder) cancer, or advanced gastric cancer. The primary endpoints of the study include overall safety, tolerability and anti-tumor activity (as measured by RECIST v1.1 assessed by independent radiology review) in PD-L1 positive tumors; secondary endpoints include progression-free survival (PFS), overall survival (OS) and duration of response. In 2014, early findings were presented for all four cohorts of the Phase 1b KEYNOTE-012 study.        

About Pembrolizumab

Pembrolizumab is the Merck investigational anti-PD-1 therapy. Pembrolizumab is being evaluated across more than 30 types of cancers, as monotherapy and in combination with other anti-cancer agents.

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-tumor immune response.

About Breast Cancer

Breast cancer is a malignant tumor that begins in the cells of the breast.¹ Worldwide, breast cancer is the most common cancer among women, with an estimated 1.67 million new cases diagnosed in 2012.² Breast cancer ranks as the fifth most common cause of cancer death worldwide.² Triple-negative breast cancer is an aggressive type of breast cancer where the cancer cells do not have estrogen or progesterone receptors and do not have too much HER2, a growth-promoting protein.³ Approximately 15 to 20 percent of breast cancer patients are diagnosed with triple-negative breast cancer.⁴

In Canada, in 2014, it is estimated that 24,400 women will be diagnosed with breast cancer. This represents 26% of all new cancer cases in women this year.  In addition, it is estimated that, 5,000 women will die from breast cancer. This represents 14% of all cancer deaths in women this year. On average, every day, 67 Canadian women will be diagnosed with breast cancer and 14 will die from this disease. In 2014, 210 men will be diagnosed with breast cancer and 60 will die from it.⁵

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 healthcare legislation in the United States and internationally; global trends toward healthcare 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 2013 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 American Cancer Society. Breast Cancer. Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003090-pdf.pdf. Accessibility verified on October 30, 2014.
² GLOBOCAN. Breast Cancer: Estimated Incidence, Mortality and Prevalence Worldwide in 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessibility verified on October 24, 2014.
³ American Cancer Society. How is breast cancer classified? Available at: http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-classifying. Accessibility verified on November 12, 2014.
⁴ Li CI et al. J Clin Oncol 2003;21:28-34
⁵ Canadian Cancer Society. Breast cancer statistics. Available at http://www.cancer.ca/en/cancer-information/cancer-type/breast/statistics/?region=on. Accessibility verified on December 8, 2014

SOURCE: Merck Canada Inc.

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