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 Rate 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

Monday, June 2, 2014 7:30 am EDT

Dateline:

CHICAGO

Public Company Information:

NYSE:
MRK
"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"

CHICAGO--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced new data from the company’s large ongoing Phase 1b study (KEYNOTE-001) evaluating pembrolizumab (MK-3475), 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 with pembrolizumab as monotherapy 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 50th 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 10th 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     ORR %

(95% CI)

    N     ORR %

(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

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 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 RECIST criteria, 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 the 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 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 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 event. 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 2014 (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 2 mg/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 pembrolizumab data being presented for advanced melanoma, see the ASCO iPlanner: https://iplanner.asco.org/am2014.

Merck Oncology Briefing Webcast

Merck will hold a webcast in conjunction with ASCO 2014 on June 2 at 6:15 p.m. CDT. Investors and journalists may access a live audio webcast of the event on Merck’s website at www.merck.com. Software needed to listen to the webcast is available on the corporate website and should be downloaded prior to the beginning of the webcast. Institutional investors, analysts and members of the media also can also listen to the event by dialing (866) 486-2604 or (706) 902-0743 and using ID code number 53194490.

About the 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 (MK-3475) 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. For information about Merck’s oncology clinical studies, please visit www.merck.com/clinical-trials.

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. 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 in 2014.

About Advanced Melanoma

Melanoma is the most serious form of skin cancer and is one of the most common types of cancer diagnosed in the U.S. While it accounts for less than two percent of skin cancer cases, melanoma is responsible for the vast majority of skin cancer deaths. In 2014, an estimated 76,100 people are expected to be diagnosed with melanoma and an estimated 9,710 people will die of the disease in the U.S.

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 Merck 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, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

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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