Merck's Pembrolizumab Significantly Improves Survival Compared to Chemotherapy in Previously-Treated Patients with Non-Small Cell Lung Cancer Whose Tumors Express Any Level of PD-L1

KEYNOTE-010 Published in The Lancet and Presented at the European Society for Medical Oncology (ESMO) Asia 2015 Congress

KIRKLAND, QC, Dec. 19, 2015 /CNW Telbec/ - Merck (NYSE: MRK), known as MSD outside Canada and the United States, today announced results from the pivotal KEYNOTE-010 study, the first study of its kind to evaluate the potential of an immunotherapy compared to chemotherapy based on prospective measurement of PD-L1 expression in patients with advanced non-small cell lung cancer (NSCLC). In the Phase 2/3 study pembrolizumab, Merck's anti-PD-1 (programmed death receptor-1) therapy, significantly improved overall survival (OS) compared to chemotherapy in patients with any level of PD-L1 expression, as defined by a tumor proportion score (TPS) of 1 percent or more. The results were published in The Lancet and will be presented at the European Society for Medical Oncology (ESMO) Asia 2015 Congress.

"Because lung cancer remains one of the most common and most challenging cancers to treat, understanding the role that pembrolizumab can play in helping patients was essential to our development program. In this study in patients with PD-L1 expression of one percent or greater, pembrolizumab demonstrably improved overall survival compared to chemotherapy in previously-treated patients with non-small cell lung cancer, including both squamous and non-squamous histologies," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories.

Overall Survival Findings from KEYNOTE-010 
The Phase 2/3 KEYNOTE-010 study included 1,034 patients with advanced NSCLC with PD-L1 expression (TPS of 1% or more). Similar findings were shown in patients who received the FDA-approved dose of pembrolizumab (2 mg/kg every three weeks) (n=345) and an investigational dose of pembrolizumab (10 mg/kg every three weeks) (n=346). Both groups of patients who received pembrolizumab were compared to patients who received docetaxel (n=343). PD-L1 expression was assessed by the immunohistochemistry companion diagnostic test PD-L1 IHC 22C3 PharmDx, made by Dako North America, Inc., an Agilent Technologies Company. The findings from KEYNOTE-010 are based on the final study analysis. The median follow-up was 13.1 months (IQR, 8.6-17.7).

In the total study population (all levels of PD-L1 expression), both doses of pembrolizumab studied significantly improved OS compared with docetaxel. Specifically, pembrolizumab resulted in a 29 percent improvement in OS for the 2 mg/kg dose (HR 0.71, P=0.0008; 95% CI, 0.58-0.88) and a 39 percent improvement in OS for the 10 mg/kg dose (HR 0.61, P<0.0001; 95% CI, 0.49-0.75), compared to docetaxel. The estimated 1-year OS rates for pembrolizumab were 43.2 percent and 52.3 percent, respectively, compared to 34.6 percent for docetaxel. Median OS for pembrolizumab were 10.4 months (95% CI, 9.4-11.9) and 12.7 months (95% CI, 10.0-17.3), respectively, compared to 8.5 months for docetaxel (95% CI, 7.5-9.8). 

Among patients with higher levels of PD-L1 expression (a TPS score of 50 percent or greater), OS was superior for both pembrolizumab doses compared with docetaxel. Specifically, pembrolizumab improved OS by 46 percent for the 2 mg/kg dose (HR 0.54, P=0.0002; 95% CI, 0.38-0.77) and by 50 percent for the 10 mg/kg dose (HR 0.50, P<0.0001; 95% CI, 0.36-0.70), compared to docetaxel. Median OS for pembrolizumab (2 mg/kg and 10 mg/kg, respectively) was 14.9 months (95% CI, 10.4 to not reached) and 17.3 months (95% CI, 11.8 to not reached), compared to 8.2 months for docetaxel (95% CI, 6.4-10.7).

Additional Findings from KEYNOTE-010
In the total study population, progression-free survival (PFS) at both doses of pembrolizumab did not meet the criterion for a statistically significant difference (HR 0.88 [95% CI, 0.74-1.05], P=0.07 for 2 mg/kg; HR 0.79 [95% CI, 0.66-0.94], P=0.004 for 10 mg/kg). Among patients treated with pembrolizumab (2 mg/kg and 10 mg/kg, respectively), median PFS was 3.9 months (95% CI, 3.1-4.1) and 4.0 months (95% CI, 2.7-4.3), compared to 4.0 months for docetaxel (95% CI, 3.1-4.2).

Patients with higher levels of PD-L1 expression (a TPS score of 50 percent or greater) who were treated with pembrolizumab had significantly prolonged PFS compared to docetaxel (HR 0.59 [95% CI, 0.44-0.78, P=0.0001] for 2 mg/kg; HR 0.59 [95% CI, 0.45-0.78, P<0.0001] for 10 mg/kg). Among patients treated with pembrolizumab (2 mg/kg and 10 mg/kg, respectively), median PFS was 5.0 months (95% CI, 4.0-6.5) and 5.2 months (95% CI, 4.1-8.1), compared to 4.1 months for docetaxel (95% CI, 3.6-4.3).

Additionally, the safety of pembrolizumab was consistent with what has been seen in previous trials among advanced lung cancer patients. Grade 3-5 treatment-related adverse events for pembrolizumab (2 mg/kg and 10 mg/kg, respectively) included: decreased appetite (n=3, n=1), fatigue (n=4, n=6), nausea (n=1, n=2), rash (n=1, n=1), diarrhea (n=2, n=0), asthenia (n=1, n=2), stomatitis (n=0, n=1), and anemia (n=3, n=1). The most common immune-mediated adverse events for pembrolizumab (2 mg/kg and 10 mg/kg, respectively) included: hypothyroidism (8% [n=28], 8% [n=28]), hyperthyroidism (4% [n=12], 6% [n=20]), and pneumonitis (5% [n=16], 4% [n=15]). There were three treatment-related deaths among patients receiving pembrolizumab at the 2 mg/kg dose (pneumonitis [n=2], pneumonia [n=1]) and three treatment-related deaths among patients receiving pembrolizumab at the 10 mg/kg dose (myocardial infarction [n=1], pneumonia [n=1], and pneumonitis [n=1]).

About KEYNOTE-010 and the Pembrolizumab Development Program
KEYNOTE-010 is a global, open-label, randomized, pivotal Phase 2/3 study (ClinicalTrials.gov, NCT01905657) evaluating two doses of pembrolizumab (2 mg/kg or 10 mg/kg every three weeks) compared to docetaxel (75 mg/m^2 every three weeks) in 1,034 patients with squamous and non-squamous NSCLC who experienced disease progression after platinum-containing systemic therapy and whose tumors expressed PD-L1.

The primary endpoints were OS and PFS. Tumor response was assessed at week 9, then every 9 weeks thereafter per RECIST 1.1 criteria by independent, central, blinded, radiographic review and investigator-assessed, immune-related response criteria.

The pembrolizumab program currently addresses more than 30 tumor types in more than 160 clinical trials, including more than 80 combinations of pembrolizumab with other cancer treatments. In lung cancer, pembrolizumab is being studied across lines of therapy, both as a monotherapy and in combination with chemotherapy.

Registration-enabling trials of pembrolizumab are currently enrolling patients in melanoma, NSCLC, head and neck cancer, bladder cancer, gastric cancer, colorectal cancer, esophageal cancer, breast cancer, Hodgkin lymphoma, multiple myeloma and other tumors, with further trials in planning for other cancers.

About KEYTRUDA® (pembrolizumab) in Canada
Pembrolizumab, known under the brand name KEYTRUDA®, is a humanized monoclonal antibody that works by increasing the ability of the body's immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

In Canada, KEYTRUDA has been approved for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab therapy and, if BRAF V600 mutation positive, following a BRAF or MEK inhibitor. An improvement in survival or disease-related symptoms has not yet been established. KEYTRUDA has been issued marketing authorization with conditions, pending the results of studies to verify its clinical benefit.

About Lung Cancer
Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon, breast, and prostate cancers combined. The two main types of lung cancer are non-small-cell (NSCLC) and small-cell. Non-small-cell and small-cell is the most common type of lung cancer, accounting for about 85 percent of all cases. The five-year relative survival rate for patients suffering from highly advanced, metastatic (Stage IV) lung cancers is estimated to be four percent.

Lung cancer is the most commonly diagnosed cancer in Canada (excluding non-melanoma skin cancers). It is the leading cause of death from cancer for both men and women in Canada. In 2015, it is estimated that 26,600 Canadians will be diagnosed with lung cancer; representing 14% of all new cancer cases, and that 20,900 Canadians will die from lung cancer, representing 27% of all cancer deaths.

In 2015, it is estimated that, on average, 73 Canadians will be diagnosed with lung cancer every day, and 57 Canadians will die from lung cancer every day.

Our Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck Oncology, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bringing new hope to people with cancer. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck in Canada
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 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 and YouTube.

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SOURCE Merck Canada Inc.

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