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Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC) with Pembrolizumab Presented at AACR Annual Meeting and Published in the New England Journal of Medicine

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Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced new data from KEYNOTE-001, a Phase 1b study evaluating pembrolizumab, the company’s investigational anti-PD-1 therapy, in naïve and previously-treated patients with advanced non-small cell lung cancer (NSCLC). In a new analysis of 313 patients from a validation data set for tumour PD-L1 expression, overall-response rate (ORR) was 45.4 percent (95% CI, 33.5-57.3) in patients with greater than or equal to (>=) 50 percent of tumour cells positive for PD-L1 expression (n=73). In the other PD-L1 subgroups, ORR was 16.5 percent (95% CI, 9.9-25.1) in patients with 1-49 percent tumour cells positive (n=103) and 10.7 percent (95% CI, 2.3-28.2) in patients with less than1 percent tumour cells positive (n=28) for PD-L1 expression. In the total study population, ORR was 19.4 percent (95% CI, 16.0-23.2) (n=495), which was consistent with data previously presented from this study. These data from KEYNOTE-001 will be presented today by Dr. Edward Garon, Jonsson Comprehensive Cancer Center, University of California, Los Angeles at the American Association for Cancer Research (AACR) Annual Meeting (abstract #CT104), were part of the AACR press program, and were also published today in the New England Journal of Medicine.

The efficacy findings demonstrated that tumour PD-L1 expression may be a relevant biomarker for the identification of NSCLC patients with an enhanced likelihood of experiencing improved efficacy with an anti-PD-1 therapy. PD-L1 is a protein that may be overexpressed in the tumour and may contribute mechanistically to an inhibited immune response.

“In this study, NSCLC patients whose tumours express PD-L1 in the majority of their cells experienced the highest response rates to pembrolizumab treatment,” said Dr. Roger Perlmutter, president, Merck Research Laboratories. “The results from this study indicate that tumour PD-L1 expression may be a relevant biomarker to identify patients more likely to have higher rates of response.”

Additional Findings from KEYNOTE-001 for the Total Evaluable Population

Data for progression-free survival (PFS) and overall survival (OS) based on tumour PD-L1 expression was also presented in 356 naïve and previously-treated patients with advanced NSCLC (total evaluable for PD-L1 staining). In the >=50 percent PD-L1 sub-group, median PFS (95% CI) was 6.3 months (2.9-12.5) (n=119); within this group, PFS was 6.1 months (2.1-12.5) for previously-treated patients (n=294) and 12.5 months (2.4-12.5) for naive patients (n=62). PFS was 3.3 months (95% CI, 2.1-4.1) in the 1-49 percent PD-L1 sub-group (n=161), and 2.3 months (95% CI, 2.1-4.0) in less than 1 percent PD-L1 sub-group (n=76). Median OS had not yet been reached in the >=50 percent PD-L1 sub-group, regardless of prior treatment. Median OS was 8.8 months for the other PD-L1 subgroups (95% CI, 6.8-12.4 for 1-49% sub-group and 5.5-12 for less than 1% sub-group, respectively), and was similar regardless of prior treatment.

Median duration of response was similar across tumour PD-L1 expression subgroups; 12.4 months (2+ to 22.8+) for >=50 percent sub-group, 10.3 months (1.4+ to 10.3) for 1-49 percent sub-group, and not reached (0.9+ to 10.8+) in the less than 1 percent sub-group. At the time of analysis, median follow-up duration was 10.9 months (range, 5.2-27.5).

“These results represent the largest data set of an anti-PD-1 therapy in naïve and previously-treated patients with advanced non-small cell lung cancer. We are advancing a broad Phase 3 program that will further characterize the potential benefit of pembrolizumab compared to the standard of care in these patients,” said Roger Dansey, therapeutic area head and senior vice president, oncology late-stage development, Merck Research Laboratories.

Adverse events evaluated in the total study population were consistent with previously reported safety data for pembrolizumab. The most common treatment-related adverse events were fatigue, pruritus, and decreased appetite. Grade 3-5 treatment-related adverse events occurred in 9.5 percent of patients (n=47). Treatment-related adverse events of an inflammatory or immune-mediated nature that occurred in more than 2 percent of patients were infusion-related reactions (n=15; 3.0%), hypothyroidism (n=34; 6.9%), and pneumonitis (n=18; 3.6%). One infusion reaction led to treatment discontinuation and all hypothyroidism cases were successfully managed with medical therapy. There was one treatment-related death (pneumonitis) and grade 3-5 pneumonitis was observed in 1.8 percent of patients (n=9). At the time of analysis, two pneumonitis cases were ongoing (both grade 1-2).

About the KEYNOTE-001 Study and Tumour PD-L1 Validation Data Set

KEYNOTE-001 is an ongoing multi-center, single-arm, open-label Phase 1b study evaluating pembrolizumab in more than 1,000 patients with diverse late-stage cancers – predominantly lung and melanoma. Three dosing regimens were evaluated; 10mg/kg every two weeks, 10mg/kg every three weeks or 2mg/kg every three weeks. The primary endpoints include ORR and safety; the secondary endpoints include PFS, OS and duration of response. Tumour response was assessed every 9 weeks per RECIST 1.1 by independent, central, blinded radiographic review. For the tumour PD-L1 expression validation data set, tumour samples were contemporaneously collected within six months of staining and tumour PD-L1 expression was measured by Dako’s immunohistochemistry companion diagnostic test PD-L1 IHC 22C3 PharmDx. The training data set for tumour PD-L1 expression from KEYNOTE-001 was presented at the AACR Annual Meeting in April 2014.

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 more than 14,000 patients – both as a monotherapy and in combination with other therapies.

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 lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most common type of lung cancer, accounting for about 85 percent of all cases. The five-year relative survival rate for all advanced or metastatic (Stage IV) lung cancers combined 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 2014, it was estimated that 26,100 Canadians would be diagnosed with lung cancer, representing 14% of all new cancer cases, and that 20,500 Canadians would die from lung cancer, representing 27% of all cancer deaths.

In 2014, it was estimated that, on average, 72 Canadians would be diagnosed with lung cancer every day, and 56 Canadians would die from lung cancer every day.(1)

About PD-L1 and PD-L1 Expression

PD-L1, also called programmed death-ligand 1, is a protein expressed on many types of cells, including some cancer cells. Under normal conditions, the interaction of PD-L1 with another protein, called programmed death receptor-1 (PD-1), serves as an important immune system checkpoint, keeping the immune system in balance and preventing the body from attacking its own cells when inflammation or an infection is present. When cancerous tumours express PD-L1, however, they are able to escape detection and destruction by cytotoxic T-cells – a type of cancer-killing immune cell – allowing the tumour to survive and grow. Tumour PD-L1 expression has been observed at varying levels across many tumour types, including breast, lung and bladder cancer. High levels of PD-L1 expression, called overexpression, are under investigation for potential use as a way to help identify patients with an enhanced likelihood to respond to certain immune-based treatment approaches.

Source: Merck