Data on Merck’s Pembrolizumab from Largest Study to Date of Investigational Anti-PD-1 Antibody in Advanced Melanoma Highlighted at ASCO 2014


June 2, 2014 6:30 am ET

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

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

“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

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

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.

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:

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 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

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

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
and connect with us on Twitter,
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 (

Ian McConnell, 973-901-5722
Claire Mulhearn, 908-423-7425
Carol Ferguson, 908-423-4465
Justin Holko, 908-423-5088

Unsubscribe from email alerts