New Data for KEYTRUDA® (pembrolizumab) in Combination with Talimogene Laherparepvec, Dabrafenib Plus Trametinib, or Low-Dose Ipilimumab in Advanced Melanoma Presented at 2016 ASCO Annual Meeting

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June 5, 2016 7:00 am ET

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced findings from three separate studies evaluating the use
of KEYTRUDA® (pembrolizumab), the company’s anti-PD-1
therapy, in combination with other treatment regimens including
talimogene laherparepvec, dabrafenib plus trametinib, or low-dose
ipilimumab in patients with advanced melanoma. These data, from
MASTERKEY-265, KEYNOTE-022, and KEYNOTE-029, respectively, are included
in the 52nd Annual Meeting of the American Society of
Clinical Oncology (ASCO) in Chicago (Abstracts #9568, #3014, and #9506).

“We continue to build on our leadership in advanced melanoma by
evaluating KEYTRUDA with multiple combination partners utilizing diverse
mechanisms of action with the goal of improving outcomes while
maintaining tolerability,” said Dr. Roger Dansey, senior vice president
and therapeutic area head, oncology late-stage development, Merck
Research Laboratories. “These encouraging early data point to the
potential for KEYTRUDA to become an important component of combination
therapy in melanoma.”

Each of these studies was designed to answer specific questions around
the use of KEYTRUDA in various combination treatment settings. In each
of the three studies, the safety profile of the combination regimens was
shown to be manageable.

“Anti-PD-1 drug therapies, like pembrolizumab, have shown benefit as a
monotherapy in the treatment of advanced melanoma, and it is important
to understand their potential in combination with other effective
therapeutics, including immunotherapies and targeted therapies,” said
Dr. Georgina Long, professor of melanoma medical oncology and
translational melanoma research, Melanoma Institute Australia and
University of Sydney. “Physicians are focused on different treatment
paths for different types of patients and, with the promising data
presented at ASCO this year, we aim to better understand the role of
monotherapy and develop combination treatment strategies for patients
with advanced melanoma who may not benefit as much from monotherapy.”

The KEYTRUDA (pembrolizumab) clinical development program includes
patients with more than 30 tumor types in more than 270 ongoing or
planned studies, including more than 100 trials that combine KEYTRUDA
with other cancer treatments – these include other immuno-oncology
therapies, standard therapies and targeted therapies.

Findings from MASTERYKEY-265: KEYTRUDA with talimogene laherparepvec
(Abstract #9568)

MASTERKEY-265 is an ongoing phase 1b study evaluating the safety,
efficacy, and tolerability of KEYTRUDA in combination with talimogene
laherparepvec in patients with previously untreated, unresectable
advanced melanoma. The trial is a collaboration between Merck and Amgen.
Talimogene laherparepvec is a herpes simplex virus-1 (HSV-1)-based
oncolytic immunotherapy used for the treatment of melanoma lesions in
the skin and lymph nodes.

Updated data from 21 evaluable patients showed that a combination of
KEYTRUDA (200 mg every two weeks) with talimogene laherparepvec (up to 4
mL of 106 PFU/mL, then 108 PFU/mL every two weeks)
resulted in a confirmed overall response rate (ORR) of 57.1 percent
(n=12/21) (95% CI, 34-78.2), per modified immune-related response
criteria (irRC) – 23.8 percent were complete responses (n=5/21) and 33.3
percent were partial responses (n=7/21).

The safety profile of KEYTRUDA in combination with talimogene
laherparepvec was consistent with that observed in previously reported
studies of KEYTRUDA or talimogene laherparepvec monotherapy in patients
with advanced melanoma. Seven patients (33%) experienced
treatment-related Grade 3-4 adverse events, including: anemia, aseptic
meningitis, autoimmune hepatitis, generalized rash, headache,
hyperglycemia, hypoglycemia, hypophosphatemia, increased alanine
aminotransferase, increased aspartate aminotransferase, increased
gamma-glutamyltransferase, muscle spasms, macular rash, rash, and
pneumonitis. Two patients (10%) experienced a treatment-related adverse
event that led to permanent discontinuation of KEYTRUDA. No patients
(0%) experienced a treatment-related adverse event that led to permanent
discontinuation of talimogene laherparepvec. No dose-limiting toxicities
were reported.

These data were presented by Dr. Long on June 4.

Findings from KEYNOTE-022: KEYTRUDA with dabrafenib plus trametinib
(Abstract #3014)

KEYNOTE-022 is an ongoing phase 1/2 study designed to assess the safety
and efficacy of KEYTRUDA in combination with dabrafenib plus trametinib
in patients with advanced melanoma. Dabrafenib (a BRAF inhibitor) and
trametinib (a MEK inhibitor) is a combination regimen used in the
treatment of certain types of advanced melanoma.

Based on early data from the 15 patients treated in phase 1, treatment
with KEYTRUDA (pembrolizumab) (2 mg/kg every three weeks) with
dabrafenib (150 mg twice daily) plus trametinib (2 mg daily) resulted in
nine partial responses, five of which were confirmed. Additionally, of
the patients with lesion data available, 92.3 percent experienced a
reduction in tumor size (n=12/13).

Grade 3-4 adverse events occurring in greater than or equal to 10
percent of patients included ALT increased (n=3), AST increased (n=3),
pyrexia (n=3), GGT increased (n=2), and WBC count decreased (n=2). Four
patients (26.7%) experienced a treatment-related adverse even that led
to discontinuation. There were no treatment-related deaths. The phase 2
part of the study is ongoing and will further evaluate the safety and
efficacy of the KEYTRUDA combination regimen compared to dabrafenib plus
trametinib.

On June 5, these data will be presented by Dr. Antoni Ribas in a poster
session from 8:00 – 11:30 a.m. CDT (Location: Hall A) and in a poster
discussion from 4:45 – 6:00 p.m. CDT (Location: Hall B1).

Findings from KEYNOTE-029: KEYTRUDA with low-dose ipilimumab
(Abstract #9506)

KEYNOTE-029 is an ongoing phase 1/2 study evaluating the safety,
efficacy, and tolerability of KEYTRUDA in combination with low-dose
ipilimumab in patients with advanced melanoma. Ipilimumab is a CTLA-4
inhibitor used in the treatment of melanoma.

Findings from 153 evaluable patients with advanced melanoma showed that
KEYTRUDA (2 mg/kg every three weeks) in combination with low-dose
ipilimumab (1 mg/kg every three weeks for four doses) demonstrated an
ORR of 57 percent (95% CI, 49-65) by independent central review – 10
percent were complete responses (n=15/153) and 47 percent were partial
responses (n=72/153). The six-month progression-free survival (PFS) rate
was 70 percent and the six-month overall survival (OS) rate was 93
percent. At the time of analysis, median PFS (95% CI, 12.4 months-NR)
and OS (95% CI, NR-NR) were not reached; 98 percent of responses were
ongoing. Median follow-up duration was 10.0 months (range 0.8-14.1).

Sixty-four patients (42%) experienced treatment-related Grade 3-4
adverse events. Thirty-eight patients (25%) experienced immune-mediated
Grade 3-4 adverse events, including: colitis, hepatitis,
hyperthyroidism, hypophysitis, infusion reaction, pancreatitis,
pneumonitis, nephritis, skin reactions, and type 1 diabetes mellitus.
Sixteen patients (10%) experienced a treatment-related adverse event
that led to ipilimumab discontinuation only, 11 patients (7%)
experienced a treatment-related adverse event that led to KEYTRUDA
(pembrolizumab) discontinuation after completion or discontinuation of
ipilimumab, and 16 patients (10%) experienced a treatment-related
adverse event that led to ipilimumab and KEYTRUDA discontinuation,
including one patient who discontinued ipilimumab for colitis and later
discontinued KEYTRUDA for increased lipase. There were no
treatment-related deaths.

These data will be presented in an oral session by Dr. Long on June 6 at
2:51 p.m. CDT (Location: Arie Crown Theater).

About KEYTRUDA

®

(pembrolizumab) Injection
100 mg

KEYTRUDA is a humanized monoclonal antibody that works by increasing the
ability of the body’s immune system to help detect and fight tumor
cells. KEYTRUDA blocks the interaction between PD-1 and its ligands,
PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both
tumor cells and healthy cells.

KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic melanoma.

KEYTRUDA is also indicated for the treatment of patients with metastatic
non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as
determined by an FDA-approved test with disease progression on or after
platinum-containing chemotherapy. Patients with EGFR or ALK genomic
tumor aberrations should have disease progression on FDA-approved
therapy for these aberrations prior to receiving KEYTRUDA. This
indication is approved under accelerated approval based on tumor
response rate and durability of response. An improvement in survival or
disease-related symptoms has not yet been established. Continued
approval for this indication may be contingent upon verification and
description of clinical benefit in the confirmatory trials.

KEYTRUDA is administered at a dose of 2 mg/kg as an intravenous infusion
over 30 minutes every three weeks for the approved indications.

Selected Important Safety Information for KEYTRUDA® (pembrolizumab)

Immune-mediated pneumonitis, including fatal cases, occurred in patients
receiving KEYTRUDA. Pneumonitis occurred in 32 (2.0%) of 1567 patients,
including Grade 1 (0.8%), 2 (0.8%), and 3 (0.4%) pneumonitis. Monitor
patients for signs and symptoms of pneumonitis. Evaluate suspected
pneumonitis with radiographic imaging. Administer corticosteroids for
Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2;
permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2
pneumonitis.

Immune-mediated colitis occurred in 31 (2%) of 1567 patients, including
Grade 2 (0.5%), 3 (1.1%), and 4 (0.1%) colitis. Monitor patients for
signs and symptoms of colitis. Administer corticosteroids for Grade 2 or
greater colitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2 or 3;
permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-mediated hepatitis occurred in 16 (1%) of 1567 patients,
including Grade 2 (0.1%), 3 (0.7%), and 4 (0.1%) hepatitis. Monitor
patients for changes in liver function. Administer corticosteroids for
Grade 2 or greater hepatitis and, based on severity of liver enzyme
elevations, withhold or discontinue KEYTRUDA.

Hypophysitis occurred in 13 (0.8%) of 1567 patients, including Grade 2
(0.3%), 3 (0.3%), and 4 (0.1%) hypophysitis. Monitor patients for signs
and symptoms of hypophysitis (including hypopituitarism and adrenal
insufficiency). Administer corticosteroids and hormone replacement as
clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or
discontinue for Grade 3 or 4 hypophysitis.

Hyperthyroidism occurred in 51 (3.3%) of 1567 patients, including Grade
2 (0.6%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 127
(8.1%) of 1567 patients, including Grade 3 (0.1%) hypothyroidism.
Thyroid disorders can occur at any time during treatment. Monitor
patients for changes in thyroid function (at the start of treatment,
periodically during treatment, and as indicated based on clinical
evaluation) and for clinical signs and symptoms of thyroid disorders.
Administer replacement hormones for hypothyroidism and manage
hyperthyroidism with thionamides and beta-blockers as appropriate.
Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3
(0.1%) of 2117 patients. Monitor patients for hyperglycemia or other
signs and symptoms of diabetes. Administer insulin for type 1 diabetes,
and withhold KEYTRUDA and administer anti-hyperglycemics in patients
with severe hyperglycemia.

Immune-mediated nephritis occurred in 7 (0.4%) of 1567 patients,
including Grade 2 (0.2%), 3 (0.2%), and 4 (0.1%) nephritis. Monitor
patients for changes in renal function. Administer corticosteroids for
Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently
discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur.
For suspected immune-mediated adverse reactions, ensure adequate
evaluation to confirm etiology or exclude other causes. Based on the
severity of the adverse reaction, withhold KEYTRUDA and administer
corticosteroids. Upon improvement to Grade 1 or less, initiate
corticosteroid taper and continue to taper over at least 1 month. Based
on limited data from clinical studies in patients whose immune-related
adverse reactions could not be controlled with corticosteroid use,
administration of other systemic immunosuppressants can be considered.
Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less
following corticosteroid taper. Permanently discontinue KEYTRUDA for any
Grade 3 immune-mediated adverse reaction that recurs and for any
life-threatening immune-mediated adverse reaction.

The following clinically significant, immune-mediated adverse reactions
occurred in less than 1% (unless otherwise indicated) of 1567 patients:
arthritis (1.6%), exfoliative dermatitis, bullous pemphigoid, uveitis,
myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis,
pancreatitis, hemolytic anemia, and partial seizures arising in a
patient with inflammatory foci in brain parenchyma.

Severe and life-threatening infusion-related reactions have been
reported in 3 (0.1%) of 2117 patients. Monitor patients for signs and
symptoms of infusion-related reactions including rigors, chills,
wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever.
For Grade 3 or 4 reactions, stop infusion and permanently discontinue
KEYTRUDA (pembrolizumab).

Based on its mechanism of action, KEYTRUDA can cause fetal harm when
administered to a pregnant woman. If used during pregnancy, or if the
patient becomes pregnant during treatment, apprise the patient of the
potential hazard to a fetus. Advise females of reproductive potential to
use highly effective contraception during treatment and for 4 months
after the last dose of KEYTRUDA.

In Trial 6, KEYTRUDA was discontinued due to adverse reactions in 9% of
555 patients; adverse reactions leading to discontinuation in more than
one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic
reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%).
Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of
patients; the most common (≥1%) was diarrhea (2.5%). The most common
adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%),
diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with
KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only
for those adverse reactions that occurred at the same or lower rate than
with KEYTRUDA.

In Trial 2, KEYTRUDA was discontinued due to adverse reactions in 12% of
357 patients; the most common (≥1%) were general physical health
deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and
generalized edema (1%). Adverse reactions leading to interruption of
KEYTRUDA occurred in 14% of patients; the most common (≥1%) were dyspnea
(1%), diarrhea (1%), and maculo-papular rash (1%). The most common
adverse reactions with KEYTRUDA vs chemotherapy were fatigue (43% with
KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs
20%), nausea (22% with KEYTRUDA), diarrhea (20% vs 20%), and decreased
appetite (20% with KEYTRUDA). Corresponding incidence rates are listed
for chemotherapy only for those adverse reactions that occurred at the
same or lower rate than with KEYTRUDA.

No formal pharmacokinetic drug interaction studies have been conducted
with KEYTRUDA.

It is not known whether KEYTRUDA is excreted in human milk. Because many
drugs are excreted in human milk, instruct women to discontinue nursing
during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA (pembrolizumab) have not been
established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology
medicines to help people with cancer worldwide. At Merck Oncology,
helping people fight cancer is our passion and supporting accessibility
to our cancer medicines is our commitment. Our focus is on pursuing
research in immuno-oncology and we are accelerating every step in the
journey – from lab to clinic – to potentially bring new hope to people
with cancer.

As part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the fastest-growing development
programs in the industry. We are currently executing an expansive
research program that includes more than 270 clinical trials evaluating
our anti-PD-1 therapy across more than 30 tumor types. We also continue
to strengthen our immuno-oncology portfolio through strategic
acquisitions and are prioritizing the development of several promising
immunotherapeutic candidates with the potential to improve the treatment
of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

For 125 years, Merck has been a global health care 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 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
health care through far-reaching policies, programs and partnerships.
For more information, visit www.merck.com
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This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the
“company”) includes “forward-looking statements” within the meaning of
the safe harbor provisions of the U.S. Private Securities Litigation
Reform Act of 1995. These statements are based upon the current beliefs
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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
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The company undertakes no obligation to publicly update any
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Please see Prescribing Information for KEYTRUDA (pembrolizumab) at 

http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

 and

Patient Information/Medication Guide for KEYTRUDA at 

http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf

.



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