Data on Merck's Pembrolizumab from Largest Study to Date of Investigational Anti-PD-1 Antibody in Advanced Melanoma Highlighted at ASCO 2014

Pembrolizumab as monotherapy shows estimated overall survival rates of 69 percent at one year across 411 advanced melanoma patients with varying stages of disease and prior therapy

Durable responses and consistent tolerability profile observed across doses, including patients with or without prior ipilimumab therapy

Phase 3 trials ongoing or planned across lines of therapy, including adjuvant treatment

CHICAGO, June 2, 2014 /CNW Telbec/ - Merck (NYSE: MRK) today announced new data from the company's large ongoing Phase 1b study (KEYNOTE-001) evaluating pembrolizumab, Merck's investigational anti-PD-1 antibody, as a single agent (monotherapy) in 411 patients with advanced melanoma. Following treatment with pembrolizumab, the estimated overall survival (OS) rate at one year was 69 percent across all patients studied, including 74 percent in patients without prior ipilimumab therapy (current standard therapy) and 65 percent in patients who had progressive disease on or following ipilimumab. At 18 months, the estimated OS was 62 percent. The median OS has not been reached, with some patients receiving treatment for more than two years.

These new data will be presented today in an oral session by Dr. Antoni Ribas, professor, Hematology/Oncology and Surgery, and director of the Tumor Immunology Program at the Jonsson Comprehensive Cancer Center, University of California, Los Angeles at the 50^th Annual Meeting of the American Society of Clinical Oncology (ASCO 2014) in Chicago (Abstract #LBA9000; 3:00 PM CDT; Location - E Arie Crown Theater).

"The data presented today provide further evidence of durable anti-tumor activity stimulated by pembrolizumab as a single agent in patients suffering from malignant melanoma," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories.  "While we await further confirmation through controlled clinical trials, the survival rates seen with pembrolizumab therapy, including in patients with advanced disease who have failed other therapies, support the use of immune manipulation in cancer care."

New Data for Pembrolizumab in Advanced Melanoma

These data from 411 patients with advanced melanoma enrolled in multiple cohorts from KEYNOTE-001, the largest Phase 1b study to date of an anti-PD-1 antibody, will be highlighted as part of the ASCO 2014 Press Program. KEYNOTE-001 involved seven advanced melanoma cohorts including patients with varying stages of disease and prior lines of therapy. At baseline, 56 percent of patients had the most advanced stage of disease (M1c) (n=232) and 77 percent of patients had received at least one prior systemic therapy (n=316). Interim data from a single cohort of 135 patients from KEYNOTE-001 were first presented at ASCO 2013 and published concurrently in the New England Journal of Medicine. More recently, updated findings from this cohort were reported at the 10^th International Congress of the Society for Melanoma Research (November 2013).

Objective Response Rates (ORR) as Assessed by irRC and RECIST Criteria among 411 Patients with Advanced Melanoma

Dose	irRC Investigator Assessment		†RECIST 1.1 Central Review
	N	^1ORR % (95% CI)	N	^1ORR % (95% CI)
Ipilimumab untreated	190	43 (36-51)	168	40 (32-48)
Ipilimumab treated	221	31 (25-37)	197	28 (22-35)
Total	411	37 (32-41)	365	34 (29-39)

Analysis cut-off: October 2013; OS analysis cut-off: May 2014
¹ Objective response rate = confirmed complete response (CR) and partial response (PR)
† Includes all treated patients with measurable disease at baseline per RECIST 1.1 central review

At the time of analysis, 88 percent (n=115/130) of reported responses in evaluable patients were ongoing and the median duration of response, by RECIST criteria, had not been reached (n=115/130) (range 6+ weeks to 76+ weeks).  The median progression-free survival (PFS), by RECISTcriteria, was 5.5 months overall (95% CI, 3.8-6.2), including 5.6 months in patients with no prior ipilimumab therapy (95% CI, 3.7-11) and 5.4 months in patients who had progressive disease on or following ipilimumab therapy (95% CI, 3.2-5.6). Anti-tumor activity was observed across all doses studied, regardless of type and number of previous treatments (including prior ipilimumab therapy), performance status, Lactate Dehydrogenase (LDH) levels, BRAF mutation status, tumor size at baseline, and anatomical site of metastatic disease. An analysis of patient subgroups indicates that lower tumor burden at baseline is a strong predictor of response to pembrolizumab.

In patients with measurable disease at baseline who had at least one on treatment scan 72 percent (n=227/317) showed tumor shrinkage, including 39 percent (n=123/317) who had tumor shrinkage of greater than 50 percent by RECIST criteria. Based on irRC (central review), 64 percent (n=204/319) of patients showed tumor shrinkage, including 31 percent (n=100/319) who showed tumor shrinkage of greater than 80 percent.

The incidence of adverse events reported was consistent with previously reported data for PEMBROLIZUMAB. The most common investigator-assessed, treatment-related adverse events were grade 1/2 and included fatigue (36%), pruritus (24%), rash (20%), diarrhea (16%) and arthralgia (16%), nausea (12%), vitiligo (11%), asthenia (9%) and cough (9%). The most common immune-related adverse events included hypothyroidism (8%) and hyperthyroidism (1%). Twelve (3%) treatment-related cases of pneumonitis were reported including one grade 3/4. The most common grade 3/4 treatment-related adverse event reported was fatigue (2%). Overall, 17 patients (4%) discontinued treatment due to investigator assessed, treatment-related adverse events. No treatment-related deaths were reported.

Dosing and Other Advanced Melanoma Data at ASCO 2014

Dosing was analyzed across all evaluable patients with advanced melanoma and a comparison of two pembrolizumab doses will be presented on Tuesday, June 3 in an oral presentation at ASCO (Abstract #3000; 9:45 AM CDT; Location - S100a). Based on these randomized data, comparing 2 mg/kg and 10 mg/kg every three weeks, and an additional cohort of randomized data comparing 10 mg/kg every two or three weeks, which is planned to be presented at a future congress, the recommended dose proposed for pembrolizumab in advanced melanoma is 2mg/kg once every three weeks.

Data evaluating pembrolizumab in advanced melanoma is the subject of additional oral presentations and a poster discussion at ASCO 2014. For additional information on data being presented for advanced melanoma, see the ASCO iPlanner: https://iplanner.asco.org/am2014.

About KEYNOTE-001 Study

The Phase 1b trial (KEYNOTE-001) is an ongoing multi-center, single-arm, open-label study evaluating pembrolizumab monotherapy in more than 1,000 patients with diverse late-stage cancers (metastatic carcinoma) - predominantly lung and melanoma. Three dosing regimens of pembrolizumab were evaluated, including 10mg/kg every two weeks, 10mg/kg every three weeks or 2mg/kg every three weeks. The primary endpoint of the study includes overall response rate (ORR) and safety; the secondary endpoints include progression-free survival (PFS), overall survival (OS) and duration of response. Tumor response in advanced melanoma was assessed every 12 weeks by investigator-assessed, immune-related response criteria (irRC), and by independent, central, blinded radiographic review per RECIST 1.1 (Response Evaluation Criteria in Solid Tumors).

About Pembrolizumab in Advanced Melanoma

Pembrolizumab is an investigational selective, humanized monoclonal anti-PD-1 antibody designed to block the interaction of PD-1 on T-cells with its ligands, PD-L1 and PD-L2, to reactivate anti-tumor immunity. Pembrolizumab exerts dual-ligand blockade of PD-1 pathway.

Pembrolizumab is being evaluated across more than 30 types of cancers, as monotherapy and in combination. Merck has a broad development program in advanced melanoma evaluating pembrolizumab across multiple stages of disease, lines of therapy and in combination with other anti-cancer agents.  The company currently has two Phase 3 studies ongoing (KEYNOTE-002, 006) in advanced melanoma, and one planned for adjuvant treatment in the same indication.

The Biologics License Application (BLA) for pembrolizumab is under priority review with the U.S. Food and Drug Administration (FDA) for the proposed indication for the treatment of patients with advanced melanoma previously-treated with ipilimumab; the PDUFA date is October 28, 2014.  In the United States, pembrolizumab has been granted FDA's Breakthrough Therapy Designation for advanced melanoma. If approved by the FDA, pembrolizumab has the potential to be the first PD-1 immune checkpoint modulator approved in this class.  The company plans to file a Marketing Authorization Application in Europe for pembrolizumab for advanced melanoma by the end of 2014.

About Advanced Melanoma

Melanoma is the most serious form of skin cancer¹ and one of a handful of cancers where the incidence in Canadians continues to increase (1.4% a year in men, 1.4% a year in women).² It was estimated that approximately 6,000 Canadians would be diagnosed with melanoma in 2013 and 1,050 would die of it. ³

About Merck Oncology: A Focus on Immuno-Oncology

At Merck Oncology, our goal is to translate breakthrough science into biomedical innovations to help people with cancer worldwide. Harnessing immune mechanisms to fight cancer is the priority focus of our oncology research and development program. The Company is advancing a pipeline of immunotherapy candidates and combination regimens. Cancer is one of the world's most urgent unmet medical needs. Helping to empower people to fight cancer is our passion. For information about Merck's commitment to Oncology visit the Oncology Information Center at http://www.mercknewsroom.com/oncology-infocenter.

About Merck

Today's Merck is a global healthcare leader working to help the world be well.  Merck is known as MSD outside the United States and Canada. 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 Medline Plus. (May 2012). Melanoma. Retrieved on May 8, 2014 from http://www.nlm.nih.gov/medlineplus/ency/article/000850.htm

² Canadian Cancer Statistics 2011 from Canadian Dermatology Association Fact Sheet. Retrieved May 8, 2014 from http://www.dermatology.ca/wp-content/uploads/2012/01/2011-Melanoma-Factsheet-EN.pdf

³ Canadian Cancer Statistics 2013. Retrieved on May 8, 2014 from http://www.cancer.ca/en/cancer-information/cancer-type/skin-melanoma/statistics/?region=on

 

 

 

SOURCE: Merck Canada Inc.

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