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June 2, 2014 6:30 am ET

Initial Therapy with Pembrolizumab Demonstrates Robust Anti-Tumor Activity with Tumor Shrinkage in 80 Percent of Evaluable PD-L1 Positive, Advanced NSCLC Patients

Merck Initiating Phase 3 Study with Pembrolizumab Versus Platinum-Based Doublet Chemotherapy as First-Line Therapy in PD-L1 Positive, Advanced NSCLC (KEYNOTE-024)

Additional 50 Patients Enrolled in KEYNOTE-001 with Analyses Planned Using Merck’s Proprietary PD-L1 Assay at One Percent and 50 Percent Cut Points

CHICAGO–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the first presentation of data evaluating pembrolizumab
(MK-3475), Merck’s investigational anti-PD-1 antibody, as initial
therapy in patients with PD-L1 positive, advanced non-small cell lung
cancer (NSCLC). In previously-untreated patients, the objective response
rate (ORR) (confirmed and unconfirmed) with pembrolizumab as a
single-agent (monotherapy) was 47 percent by investigator-assessed,
immune-related response criteria (irRC) (n=21/45: 95% CI, 32-62) and 26
percent by centrally evaluated RECIST v1.1 (Response Evaluation Criteria
in Solid Tumors) (n=11/42: 95% CI, 14-42). In evaluable patients who had
measurable disease with one post baseline scan, 80 percent demonstrated
tumor shrinkage as measured by centrally evaluated RECIST criteria
(n=28/35). The median duration of response has not been reached, with
some patients continuing on treatment with pembrolizumab as monotherapy
for at least one year.

These new data, from the company’s large ongoing Phase 1b study
(KEYNOTE-001), will be presented today in an oral session by Dr. Naiyer
Rizvi, medical oncologist, Thoracic Oncology Service, Memorial Sloan
Kettering Cancer Center, at the 50^th Annual Meeting of the
American Society of Clinical Oncology (ASCO 2014) in Chicago (Abstract
#8007; 3:00 PM CDT; Location – E Hall D2).

“These initial data show that early use of pembrolizumab as monotherapy
provides robust anti-tumor activity in patients with
previously-untreated, advanced non-small cell lung cancer,” said Dr.
Rizvi. “Today, there are few options for people with advanced lung
cancer and early data suggests that pembrolizumab, which activates the
body’s immune system to target cancer cells, may be a promising new
approach.”

First Data for Pembrolizumab as Initial Therapy in Advanced Lung
Cancer

Data to be presented from a cohort of KEYNOTE-001, the largest Phase 1b
study to date of an anti-PD-1 antibody, evaluated pembrolizumab
monotherapy as initial therapy in patients with stage IV NSCLC who had
no prior systemic therapy and whose tumors were assessed as positive for
PD-L1 expression. As measured by Merck’s proprietary,
immunohistochemistry (IHC) trial assay, tumors 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 tumor stroma. In the study cohort, 78 percent
of evaluable advanced NSCLC patients were determined to be PD-L1
positive (n=57/73).

Objective Response Rates (ORR) and Disease Control Rates (DCR) in
Advanced NSCLC, as Assessed by irRC and RECIST Criteria

Analysis cut-off date: 03 March 2014
Objective response rate =
confirmed complete response and partial response
Disease control
rate = complete response, partial response, and stable disease
¹3
patients did not have measurable disease by RECIST v1.1 per independent
central review at baseline and were not evaluated for response using
this criteria
†Includes confirmed and unconfirmed responses

At the time of analysis, 90 percent (n=19/21) and 100 percent (n=11/11)
of overall responses (confirmed and unconfirmed) in evaluable patients
were ongoing by irRC and RECIST criteria, respectively. None of the
responders discontinued treatment due to progression of disease. The
interim, median progression-free survival (PFS) was 37 weeks by irRC
(95% CI, 27.0-NR) and 27 weeks by RECIST (95% CI, 13.6-45.0). The
interim, median duration of treatment among evaluable patients with
ongoing responses was 27.1 weeks based on both measurement criteria
(irRC range, 6.1 – 57.1+) (RECIST range, 15.0+ – 48.3+).

Adverse events were consistent with previously reported data for
pembrolizumab. The most common investigator-assessed, treatment-related,
adverse events (greater than 5 percent) included fatigue (22%), pruritus
(13%), hypothyroidism (9%), dermatitis acneiform (7%), diarrhea (7%),
dyspnea (7%), and rash (7%). Investigator-designated, treatment-related,
adverse events resulting in discontinuation were pneumonitis (one grade
3) and acute kidney injury (one grade 2). Other investigator-designated,
treatment-related, adverse events included pericardial effusion (one
grade 3) and elevated blood creatine phosphokinase levels (one grade 4).

New Studies in PD-L1 Positive, Advanced Lung Cancer

Based on these data, Merck has enrolled 50 additional patients in the
KEYNOTE-001 study with previously-untreated, advanced NSCLC with PD-L1
positive-staining tumors. For this cohort, cut points of greater than or
equal to one percent and 50 percent tumor cells stained will be
evaluated as part of the efficacy analysis. Additionally, Merck plans to
initiate a Phase 3 study (KEYNOTE-024) evaluating pembrolizumab
monotherapy versus platinum-based doublet chemotherapy (cisplatin,
carboplatin combined with either: docetaxel, paclitaxel, vinorelbine,
gemcitabine or irinotecan) in previously-untreated patients with PD-L1
positive, advanced NSCLC in September 2014.

“As clinical experience with pembrolizumab grows in advanced non-small
cell lung cancer we are seeing durable responses across multiple lines
of therapy, including in the first-line treatment setting,” said, Dr.
Roy Baynes, senior vice president, Global Clinical Development, Merck
Research Laboratories. “Exploring the clinical utility of tumor
characteristics, such as expression of PD-L1 as a potential marker for
patient selection or study enrichment, is an important part of our
research program in this disease.”

Additional Advanced Lung Cancer Data at ASCO 2014

New
data evaluating pembrolizumab in previously-treated NSCLC including
findings from an additional study cohort will be presented in a poster
discussion on Tuesday, June 3 (Abstract #8020; 8:00 AM CDT; Location –
E354b). For more information about data in advanced NSCLC, see the ASCO
iPlanner: https://iplanner.asco.org/am2014.

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 www.merck.com. 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 pembrolizumb 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 NSCLC was evaluated
every 9 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 Lung Cancer

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 the PD-1 pathway.

Pembrolizumab is being evaluated across more than 30 types of cancers,
as monotherapy and in combination. Merck is advancing a clinical program
in advanced NSCLC evaluating pembrolizumab as monotherapy and in
combination across lines of therapy, and is exploring different tumor
characteristics such as PD-L1 expression as predictors of
responsiveness. For information about Merck’s oncology clinical studies,
please click here.

About Lung Cancer

Lung cancer has been the most common cancer in the world, other than
skin cancer. In the U.S. there will be an estimated 159,260 deaths from
lung cancer in 2014. Lung cancer is divided into two major types:
non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).
NSCLC is the most common type of lung cancer – accounting for > 85
percent of all lung cancers.

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 an early and
late-stage 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 http://www.mercknewsroom.com/oncology-infocenter.

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,
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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 (www.sec.gov).

Merck
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