Early Findings Exploring the Relationship of PD-L1 Expression and Clinical Outcomes with MK-3475, Merck’s Investigational Anti-PD-1 Immunotherapy, Presented at AACR Annual Meeting 2014


April 6, 2014 9:30 am ET

Exploratory Analyses in Advanced Melanoma and NSCLC Presented in Oral Session

Dr. Roger Perlmutter to Present at AACR Opening Plenary Session

WHITEHOUSE STATION, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced the presentation of early findings from studies
exploring the relationship between tumor PD-L1 expression and clinical
outcomes following monotherapy treatment with MK-3475, an
investigational anti-PD-1 immunotherapy, in patients with advanced
melanoma and advanced non-small cell lung cancer (NSCLC). Responses were
observed in patients with PD-L1 negative tumors; although the
preliminary findings for both tumor types suggest that higher PD-L1
expression was associated with higher overall response rates. Further
study of the relationship between PD-L1 expression and responses to
MK-3475 as monotherapy and in combination with other treatments for
melanoma, NSCLC and other tumors is ongoing or planned.

These findings will be presented today in an oral session at the AACR
Annual Meeting 2014 in San Diego and were highlighted within the
official AACR press program. Separately, as part of today’s opening
plenary session, Dr. Roger M. Perlmutter, president, Merck Research
Laboratories, will deliver a plenary lecture entitled “Tumor-Specific
Immune Activation: Immuno-Oncology Comes of Age”.

“These exploratory analyses are providing us with insightful information
regarding the association of PD-L1 expression and clinical outcomes with
MK-3475,” said Dr. Eric Rubin, vice president, Oncology, Merck Research
Laboratories. “In both types of advanced cancers studied, we are seeing
durable responses in a wide range of patients, including those with
PD-L1 negative tumors. We will continue to explore PD-L1 expression and
other selection markers across tumors in our MK-3475 development

Preliminary PD-L1 Expression Analysis in Advanced Melanoma

Preliminary findings on PD-L1 expression in 125 evaluable advanced
melanoma patients, based on a minimum of 6-month follow-up from the
ongoing Phase 1B KEYNOTE-001 study, were presented by Dr. Adil Daud,
co-director of the University of California, San Francisco (UCSF)
Melanoma Center, and director of melanoma clinical research at the UCSF
Helen Diller Family Comprehensive Cancer Center, (abstract #5013).
Results from the preliminary analysis showed that 71 percent (n=89) of
advanced melanoma patients had positive PD-L1 tumors at the optimally
defined cut-point of ≥1 percent of tumor cells stained, as measured by
immunohistochemistry (IHC). An additional cut-point of ≥10 percent of
cells stained by IHC measurement was also evaluated.

In the overall evaluable advanced melanoma population, the overall
response rate was 40 percent (n=113) as measured by RECIST 1.1 (Response
Evaluation Criteria in Solid Tumors). Based on the ≥1 percent cut-point,
responses were observed in 49 percent [95% CI; range 38-61] (n=83) (per
RECIST criteria) of patients with positive PD-L1 tumors and 13 percent
[95% CI; range 4-31] (n=30) of patients with PD-L1 negative tumors. When
the ≥10 percent cut-point was used, responses were observed in 52
percent [95% CI; range 40-65] (n=65) of patients with PD-L1 positive
tumors and 23 percent [95% CI; range 12-37] (n=48) of patients with
PD-L1 negative tumors.

The high prevalence of PD-L1 expression, along with the responses
observed in the overall population and patients with PD-L1 positive
tumors based on the ≥1 percent cut-point, suggest that selecting
patients for MK-3475 therapy based on measurement of PD-L1 is of limited
utility in this tumor. Preliminary findings for overall disease control
rates, median estimated progression-free survival (PFS), and median
estimated overall survival (OS) were also presented.

Preliminary PD-L1 Expression Analysis in Advanced NSCLC

Preliminary findings on PD-L1 expression in 129 evaluable
previously-treated patients with advanced NSCLC, based on a minimum of
19-week follow-up from the ongoing KEYNOTE-001 study, were presented by
Dr. Leena Gandhi, assistant professor of medicine at Harvard Medical
School and thoracic oncologist at Dana-Farber Cancer Institute (abstract
#5014). Results from the preliminary analysis showed that approximately
45 percent of advanced NSCLC patients had positive PD-L1 tumors at a
cut-point of ≥1 percent of tumor cells stained as defined by IHC
assessment. Based on this data set, the preliminary analysis suggests
that the optimal cut-point is ≥50 percent of tumor cells stained by IHC
assessment. When using this measurement, approximately 25 percent of
advanced NSCLC patients had tumors that strongly expressed PD-L1.

In the overall evaluable advanced NSCLC population, the overall response
rate was 19 percent (n=129) (per RECIST criteria). In evaluable
PD-L1-positive strong expresser population, responses were seen in 37
percent [95% CI; range 22-53] (n=15/41) (per RECIST criteria) of these
patients, with responses also observed in 11 percent [95% CI; range
6-20] (n=10/88) of patients with PD-L1 low or negative tumors. When the
≥1 percent cut-point was used, responses were observed in 25 percent
[95% CI; range 17-36] (n=22/87) of evaluable patients with PD-L1
positive tumors and 7 percent [95% CI; range 2-20] (n=3/42) of patients
with PD-L1 negative tumors. Preliminary data on estimated median PFS and
estimated median OS were also presented.

No adverse events were presented as part of these exploratory analyses
and were consistent with those previously reported for MK-3475.

Additional Merck Oncology Data Presentations at AACR 2014

Additional Merck research presented at AACR include the following
abstracts (presented as posters on Wednesday, April 9):

  • mDX400, the murine analog against MK-3475 is active in
    immunocompetent, autochthonous murine models of melanoma and breast
    cancer (Abstract #5024)
  • Dissecting the dynamics of anti-PD1 immunotherapy in preclinical tumor
    models (Abstract #5025)

About MK-3475

Many tumors are able to evade the immune system through a mechanism that
exploits the PD-1 inhibitory checkpoint protein. MK-3475 is an
investigational, highly selective anti-PD-1 immunotherapy designed to
restore the ability of the immune system to recognize and target cancer
cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of
the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the
immune system’s T-cells that target cancer, essentially by releasing a
brake on the immune system.

MK-3475 is being studied in 15 clinical trials estimated to enroll more
than 4,000 patients across more than 30 types of cancer. Additional
trials, both as monotherapy and in combination with other cancer
therapies, are planned. For information on ongoing MK-3475 clinical
trials please visit http://www.merck.com/clinical-trials

Merck announced Breakthrough Therapy designation for MK-3475 in advanced
melanoma by the U.S. Food and Drug Administration in April 2013. Merck
announced in January the initiation of a rolling submission of a
Biologics License Application for MK-3475 in advanced melanoma in the
U.S. The company expects to complete the submission in the first half of

About Advanced Melanoma

There were an estimated 232,000 new cases of melanoma diagnosed in 2012
worldwide. Melanoma is the most dangerous type of skin cancer and is the
leading cause of death from skin disease. While it accounts for only
five percent of all cases, melanoma is the cause of the vast majority of
skin cancer deaths. According to the American Cancer Society, an
estimated 9,480 people in the U.S. died from advanced melanoma in 2013.

About Lung Cancer

Lung cancer is the leading cause of cancer death worldwide in both men
and women, with an estimated 1.5 million deaths worldwide each year,
according to the American Cancer Society. NSCLC is the most common type
of lung cancer representing about 85 percent of all lung cancer

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 www.merck.com
and connect with us on Twitter,
and YouTube.

Merck 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 (www.sec.gov).

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

Unsubscribe from email alerts