Additional Interim Data for Merck’s Investigational Anti-PD-1 Immunotherapy, MK-3475, Shows Estimated Overall Survival Rate of 81 Percent at One Year in Patients with Advanced Melanoma


November 18, 2013 12:00 pm ET

Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced additional data for MK-3475, an investigational
anti-PD-1 immunotherapy, in patients with advanced melanoma that showed
an estimated overall survival rate of 81 percent at one year across all
MK-3475 monotherapy doses evaluated. This is the first time overall
survival data have been presented from the cohort of 135 patients with
advanced melanoma enrolled in Merck’s ongoing Phase IB clinical trial
(PN 001) for MK-3475. Researchers presented the findings today in an
oral plenary session at the 10th International Congress of the Society
for Melanoma Research in Philadelphia.

“New agents are needed for patients with advanced melanoma,” said Dr.
Caroline Robert, head of Dermatology at Gustave Roussy, Cancer Campus,
Grand Paris. “I am excited by the results seen for MK-3475 to date as a
single agent and believe these findings support further study both as a
monotherapy and in combination in various solid tumors.”

The objective response rate (patients who had either a complete or
partial response) across all doses improved with longer duration of
follow-up; at the time of this analysis, the objective response rate was
41 percent (9 percent complete response rate), as evaluated by a blinded
central review committee using RECIST 1.1 (Response Evaluation Criteria
in Solid Tumors). While the majority of responses to MK-3475 treatment
occurred early (within the first 12 weeks), responses and changes from
partial to complete response continued to occur after six months of
treatment. Partial and complete responses occurred as late as 48 and 70
weeks. Median duration of response and median overall survival have yet
to be reached for any dose evaluated.

“These results provide further insight into the therapeutic properties
of MK-3475 in patients with advanced melanoma,” said Dr. Roger M.
Perlmutter, president, Merck Research Laboratories. “Simply put, our
data make us hopeful that this novel investigational therapy could
potentially provide meaningful benefits to patients suffering from this
malignant disease.”

Phase 1B Trial (PN 001) Trial Design

The Phase IB trial (PN 001) is an ongoing multi-center, single-arm,
open-label study evaluating MK-3475 monotherapy in more than 1,000
patients with diverse late-stage cancers (metastatic
carcinoma)—predominantly lung and melanoma. Three dosing regimens of
MK-3475 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 is overall response rate and the secondary endpoints are
progression-free survival and overall survival as measured by
immune-related response criteria and centrally evaluated RECIST criteria.

Additional Results for MK-3475 in Advanced Melanoma

This additional analysis provides approximately five months of follow-up
for objective response rate beyond the interim results for MK-3475 from
the 135 patients in the advanced melanoma cohort presented at the 2013
American Society of Clinical Oncology (ASCO) Annual meeting and
published in the New England Journal of Medicine. In addition,
this is the first time overall survival and progression-free survival
have been presented from this study.

The previously reported objective response rate across all doses was 38
percent (CI 95%: 25 to 44 percent) (per RECIST criteria). In the
analysis presented today, the overall response rate was 41 percent (CI
95%: 32 to 51 percent), reflecting additional responses to MK-3475. In
addition, 88 percent (43/49) of patients with a partial or complete
response showed no evidence of disease progression. Similar response
rates were observed between ipilimumab-pretreated and ipilimumab-naïve

At this analysis, the maximum ongoing duration of response recorded was
65 weeks (range 8+ to 65+). The disease control rate across doses for
patients in the melanoma cohort was 61 percent (CI 95%: 52 to 70
percent), and median progression-free survival at time of analysis was
36 weeks. The rates of treatment-related adverse events were consistent
with those previously observed and included: fatigue (37%), pruritus
(26%), rash (22%), diarrhea (21%), arthralgia (17%), vitiligo (14%),
headache (13%), nausea (12%), asthenia (11%), myalgia (11%) and AST
increase (10%). Grade 3–4 treatment-related adverse events that occurred
in more than one patient were AST increase, fatigue, rash and renal
failure (n=2 each).

Clinical Development of MK-3475 in Advanced Melanoma

Merck has completed enrollment in a Phase II registration trial (PN 002)
comparing two doses of MK-3475 versus chemotherapy in patients with
advanced melanoma who have progressed after prior therapy (see
A Phase III registration trial of MK-3475 versus ipilimumab in
ipilimumab-naïve patients with advanced melanoma is ongoing (see
The company plans to initiate combination trials this year and in early
2014 in melanoma and other cancers.

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 natural 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 by essentially
releasing a brake on the immune system.

MK-3475 is currently being studied in eight clinical trials estimated to
enroll over 3,000 patients across a broad range of cancer types,
including: bladder, colorectal, gastric, head and neck, melanoma,
non-small cell lung, triple negative breast and hematological
malignancies. Additional trials, both as monotherapy and in combination
with other cancer therapies, are planned. The expansion of the MK-3475
clinical development program is based on preliminary clinical evidence
from Merck’s large foundational Phase IB trial (PN 001) evaluating
MK-3475 monotherapy in more than 1,000 patients with diverse late-stage
cancers (metastatic carcinoma).

About Breakthrough Therapy Designation

In April 2013, Merck announced that MK-3475 received a Breakthrough
Therapy Designation for advanced melanoma from the U.S. Food and Drug
Administration (FDA). This designation for an investigational drug is
intended to expedite the development and review of a candidate that is
planned for use, alone or in combination, to treat a serious or
life-threatening disease or condition when preliminary clinical evidence
indicates that the drug may demonstrate substantial improvement over
existing therapies on one or more clinically significant endpoints. The
U.S. FDA Safety and Innovation Act includes a provision that allows
sponsors to request that an investigational drug be designated as a
Breakthrough Therapy.

About Advanced Melanoma

Over one million new cases of skin cancer are diagnosed each year, and
melanoma is the most dangerous type of skin cancer. While it accounts
for only 5 percent of all cases, melanoma is the cause of 75 percent of
skin cancer deaths. According to the American Cancer Society, an
estimated 9,180 people in the U.S. died from advanced melanoma in 2012.

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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Ian McConnell, 908-423-3046
Claire Mulhearn, 908-423-7425
Carol Ferguson, 908-423-4465
Justin Holko, 908-423-5088

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