KIRKLAND, QC, April 19, 2015 /CNW Telbec/ - 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.
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 health care
legislation in the United States
and internationally; global trends toward health care 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 2014 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).
# # #
1 Canadian Cancer Society. Lung Cancer.
[https://www.cancer.ca/en/cancer-information/cancer-type/lung/statistics/?region=on],
accessed on April 18, 2015.
SOURCE Merck