First Presentation of Early Data for Pembrolizumab (MK-3475), Merck’s Investigational Anti-PD-1 Antibody, in Advanced Head and Neck Cancer at ASCO 2014


June 1, 2014 8:23 am ET

Overall Response Rate of 20 Percent for Pembrolizumab as Single Agent in Patients with Advanced Head and Neck Cancer

Merck Initiating Phase 3 Study in Advanced Head and Neck Cancer with Pembrolizumab Versus Standard of Care in Q3 2014 (KEYNOTE-040)

Additional 110 Patients with Advanced Head and Neck Cancer to be Enrolled in KEYNOTE-012 with Assessment of PD-L1 Tumor Levels Planned

Pembrolizumab Announced as New Generic Name for MK-3475

CHICAGO–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the first presentation of early findings from a Phase 1b
study (KEYNOTE-012) evaluating pembrolizumab (MK-3475), Merck’s
investigational anti-PD-1 antibody, as a single-agent (monotherapy) in
patients with PD-L1 positive, advanced head and neck cancer. Early data
showed a best overall response rate of 20 percent (confirmed and
unconfirmed) (n=11/56) (95% CI, 10.2- 32.4) with 29 percent of patients
having stable disease as measured by RECIST criteria (n=16/56) (95% CI,
17.3-42.2). Similar overall response rates were observed in Human
papillomavirus (HPV)-positive and HPV-negative patients – HPV infection
is a risk factor for some types of head and neck cancer. In the study,
tumor shrinkage was demonstrated in 51 percent of evaluable patients who
had measurable disease with one post baseline scan, per RECIST criteria

These early findings will be presented today in an oral session by Dr.
Tanguy Seiwert, associate director of the Head and Neck Cancer Program
and assistant professor of medicine at The University of Chicago, at the
50th Annual Meeting of the American Society of Clinical
Oncology (ASCO 2014) in Chicago (Abstract #6011; Sunday, June 1; 11:30AM
CDT; Location – S100bc).

“Recurrent and metastatic head and neck cancer carries a very poor
prognosis, and often is accompanied by poor quality of life and
disfigurement. Additional treatment options are urgently needed,” said
Dr. Seiwert. “These early response data with pembrolizumab as
monotherapy provide an encouraging proof of concept and support further
study of this novel investigational immunotherapy in this hard-to-treat
cancer type.”

“We continue to observe robust signals of anti-tumor activity in
response to pembrolizumab monotherapy across multiple tumor types and
lines of therapy, including these data in head and neck cancer,” said
Dr. Roy Baynes, senior vice president, global clinical development,
Merck Research Laboratories. “The breadth of data to be presented at
ASCO underscores why Merck is advancing a broad development program for
pembrolizumab across more than 30 tumor types, including late-stage
studies in head and neck and other cancers.”

Early Findings for Pembrolizumab in Advanced Head and Neck Cancer

Data to be presented from a cohort of KEYNOTE-012, a Phase 1b study
across four solid tumor types, evaluated pembrolizumab monotherapy dosed
at 10 mg/kg every two weeks in patients with advanced (locally recurrent
and/or distant metastatic) head and neck cancer whose tumors were
assessed as positive for PD-L1 expression using Merck’s proprietary
immunohistochemistry (IHC) trial assay. Fifty-six patients were
evaluable for response, of which 20 tested positive for HPV, 36 tested
negative (or were unevaluable) for HPV. The majority of patients studied
had received two or more prior lines of therapy.

Best Overall Response Rates in Advanced Head and Neck Cancer

Patients Evaluable
for Response


Total Head/neck


HPV Positive


HPV Negative

Response Evaluation

n (%)

  95% CI n (%)   95% CI n (%)   95% CI
Complete Response 1 (2) (0.0, 9.6) 1 (5) (0.1, 24.9) 0 (0) (0.0, 9.7)
Partial Response 10 (18) (8.9, 30.4) 3 (15) (3.2, 37.9) 7 (19) (8.2, 36.0)
Best Overall Response

(Complete + Partial)**

11 (20) (10.2, 32.4) 4 (20) (5.7, 43.7) 7 (19) (8.2, 36.0)
Stable Disease 16 (29) (17.3, 42.2) 8 (40) (19.1, 63.9) 8 (22) (10.1, 39.2)
Progressive Disease 25 (45) (31.3, 58.5) 7 (35) (15.4, 59.2)

18 (50)

(32.9, 67.1)
No Assessment 4 (7) (2.0, 17.3) 1 (5) (0.1, 24.9) 3 (8.3) (1.8, 22.5)

Analysis cut-off date: 23 May 2014

Based on RECIST 1.1 Per site assessment; includes confirmed and
unconfirmed responses

* 61 patients eligible for treatment; 60 patients dosed; 56
patients eligible for pre-defined full analysis set.

** A single patient with progressive disease followed by partial
response (PR) on treatment was classified as PR.

*** Includes 2 patients for whom HPV data unavailable.

Based on binomial exact confidence interval method.

Of advanced head and neck patients screened, 78 percent (n=81/104) were
classified as PD-L1 positive based on greater than or equal to one
percent of tumor cells demonstrating expression of the PD-L1 marker, or
any positive staining with the same reagent in the tumor stroma.
Employing a preliminary assay cut-point, evidence of a relationship was
observed for the level of PD-L1 staining and the overall response rate
(above cut-point: 45 percent (n=5/11); below cut-point: 11 percent

Adverse events reported were consistent with previously reported data on
pembrolizumab. The most common treatment-related adverse events
(occurring in greater than or equal to 5% of patients) included fatigue
(17%), pruritus (10%), rash (7%), nausea (7%), myalgia (5%), and
decreased appetite (5%). There was one treatment-related grade 3 rash

New Nonproprietary Name: Pembrolizumab

Merck recently announced
the nonproprietary name for MK-3475 is pembrolizumab
. This follows
the review of pembrolizumab by both the United States Adopted Names
Council and the International Nonproprietary Names Programme of the
World Health Organization. Pembrolizumab replaces the previously
proposed name, lambrolizumab.

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 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 can
also listen to the event by dialing (866) 486-2604 or (706) 902-0743 and
using ID code number 53194490.

About the KEYNOTE-012 Study

KEYNOTE-012 is an ongoing multi-center, non-randomized Phase 1b trial
evaluating the safety, tolerability and anti-tumor activity of
pembrolizumab monotherapy in patients with advanced triple negative
breast cancer (TNBC), advanced head and neck cancer, advanced urothelial
cancer, or advanced gastric cancer. Two dosing regimens of pembrolizumab
are being evaluated, 10mg/kg every 2 weeks and 200 mg IV once every 3
weeks. The primary endpoints of the study include overall safety and
tolerability, and anti-tumor activity (as measured by RECIST 1.1
[Response Evaluation Criteria in Solid Tumors]) in PD-L1 positive
tumors; secondary endpoints include progression-free survival (PFS),
overall survival (OS), duration of response and subgroup analyses by HPV

An additional 110 patients with advanced head and neck cancer are
planned to be enrolled in KEYNOTE-012. Analyses of tumor PD-L1 levels
are planned.

About Pembrolizumab

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.

Today, pembrolizumab is being evaluated across more than 30 types of
cancers, as monotherapy and in combination. It is anticipated that by
the end of 2014, the pembrolizumab development program will grow to more
than 24 clinical trials across 30 different tumor types, enrolling an
estimated 6,000 patients at nearly 300 clinical trial sites worldwide,
including new Phase 3 studies in head and neck and other cancers. For
information about Merck’s oncology clinical studies, please click here.

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 Head and Neck Cancer

Head and neck cancers are a related group of cancers that involve the
oral cavity, pharynx and larynx. Most head and neck cancers are squamous
cell carcinomas that begin in the flat, squamous cells that make up the
thin surface layer (epithelium) of the head and neck (called the). The
leading risk factors for head and neck cancer include tobacco and
alcohol use. Infection with certain types of HPV, also called human
, is a risk factor for some types of head and neck
cancer, specifically cancer of the oropharynx, which is the middle part
of the throat including the soft palate, the base of the tongue, and the
tonsils. Each year there are approximately 400,000 cases of cancer of
the oral cavity and pharynx, with 160,000 cancers of the larynx,
resulting in approximately 300,000 deaths.

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

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
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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
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