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June 5, 2017 6:05 am ET

Data to Be Presented at 2017 ASCO Annual Meeting Include Findings in Patients with Locally Advanced Triple-Negative (TNBC) and Hormone Receptor-Positive/HER2-Negative (HR+/HER2-) Breast Cancers

Merck (NYSE:MRK), known as MSD outside the United States and Canada, and
QuantumLeap Healthcare Collaborative, today announced results from the
Phase 2 I-SPY 2 TRIAL investigating KEYTRUDA^®
(pembrolizumab), Merck’s anti-PD-1 therapy, in combination with standard
therapy [paclitaxel followed by doxorubicin and cyclophosphamide (AC)]
as a neoadjuvant (pre-operative) treatment for patients with locally
advanced triple-negative breast cancer (TNBC) or hormone
receptor-positive/HER2-negative (HR+/HER2-) breast cancer. Findings
showed that the addition of KEYTRUDA increased the estimated pathologic
complete response (pCR) rate nearly threefold in patients with TNBC (60%
vs 20%) and in patients with HR+/HER2- breast cancer (34% vs 13%)
compared to standard therapy. Overall, based on Bayesian predictive
probability of success in a confirmatory Phase 3 trial, KEYTRUDA has
graduated from the I-SPY 2 TRIAL for all signatures in which it was
tested (TNBC, all HER2-, and HR+/HER2-). Data will be presented today by
Dr. Rita Nanda, The University of Chicago, during an oral session at the
2017 American Society of Clinical Oncology (ASCO) Annual Meeting in
Chicago (Abstract #506) and will also be presented in subsequent “Best
of ASCO” events scheduled throughout the year.

“KEYTRUDA in combination with standard therapy tripled the rate of
pathologic complete responses in HER2- patients in the I-SPY 2 Trial,”
said Laura J. Esserman, M.D., MBA, professor of surgery and radiology
and director of the Carol Franc Buck Breast Care Center at UCSF Helen
Diller Family Comprehensive Cancer Center, and the overall principal
investigator for the I-SPY TRIALS. “The regimen indicates a new and
important treatment pathway and gives us well-grounded hope for new
options for patients with these aggressive breast cancers – and that’s
potentially very good news.”

“We recognize that there is a critical unmet need for patients with
certain breast cancer subtypes and believe that combination regimens
will be important to advancing patient care,” said Dr. Eric Rubin, vice
president of early-stage development, clinical oncology, Merck Research
Laboratories. “The results presented at ASCO, which add to the growing
body of evidence for KEYTRUDA in various types of breast cancer, are
exciting and demonstrate the potential benefit of KEYTRUDA in these
patients.”

The I-SPY 2 TRIAL (NCT01042379), sponsored by QuantumLeap Healthcare
Collaborative, is a standing Phase 2 randomized, controlled,
multi-center trial for women with newly diagnosed, locally advanced
breast cancer (Stage II/III), and is designed to screen promising new
treatments and identify which therapies are most effective in specific
patient subgroups based on molecular characteristics (biomarker
signatures). The trial is an adaptive study design assessing the
combination of biologically targeted investigational drugs with standard
chemotherapy in the neoadjuvant setting, compared to standard
chemotherapy alone. The primary endpoint is to determine whether the
combination of certain therapies increases the probability of pCR in the
breast and the lymph nodes at the time of surgery. The data presented at
ASCO from the I-SPY 2 TRIAL were based on results observed in patients
at high risk of relapse using up-front tumor profiling (including HR
status, HER2 status, and the MammaPrint 70-gene signature test).
Patients were treated with weekly standard chemotherapy (paclitaxel) for
12 weeks, with or without KEYTRUDA (pembrolizumab), followed by
doxorubicin and cyclophosphamide (AC) every 3 weeks for four cycles.
Sixty-nine patients were adaptively randomized to receive KEYTRUDA in
the trial from December 2015 until it graduated in November 2016. In
total, 46 patients have undergone surgery; the other 23 have on-therapy
MRI assessments.

In patients with TNBC, an absolute increase in the estimated pCR rate of
40 percent was observed in the KEYTRUDA arm (based on the estimated pCR
rate of 60% with KEYTRUDA plus standard therapy compared to 20% with
standard therapy alone). In patients with HER2- breast cancer, an
absolute increase in the estimated pCR rate of 30 percent was observed
in the KEYTRUDA arm (based on the estimated pCR rate of 46% with
KEYTRUDA plus standard therapy compared to 16% with standard therapy
alone). In patients with HR+/HER2- breast cancer, an absolute increase
in the estimated pCR rate of 21 percent was observed in the KEYTRUDA
(pembrolizumab) arm (based on the estimated pCR rate of 34% with
KEYTRUDA plus standard therapy compared to 13% with standard therapy
alone). The Bayesian model estimated pCR rates appropriately adjust to
characteristics of the I-SPY 2 population, including MammaPrint status.

The safety profile of KEYTRUDA was consistent with that observed in
previously reported studies across tumors. In the KEYTRUDA arm, Grade
3-5 treatment-related adverse events include diarrhea (n=5), febrile
neutropenia (n=5), fatigue (n=4), anemia (n=3), nausea (n=3),
neutropenia without fever (n=1), peripheral motor neuropathy (n=1),
peripheral sensory neuropathy (n=1) and vomiting (n=1). Immune-mediated
adverse events of Grade 3-5 include adrenal insufficiency (n=5),
hepatitis (n=2), colitis (n=1) and hypothyroidism (n=1). Five of six
patients presented with adrenal insufficiency after completion of AC
(21-24 weeks after starting KEYTRUDA), and one presented during KEYTRUDA
treatment (5 weeks after starting KEYTRUDA).

“Not all breast cancers are the same – and there has continued to be a
significant gap in the treatment options available for patients with
certain subtypes, particularly TNBC,” said Dr. Rita Nanda, medical
oncologist at The University of Chicago. “The results observed in this
trial are not only encouraging, but demonstrate the potential for
treatment combinations that can make a difference in patient outcomes.”

About I-SPY and the I-SPY 2 TRIAL

The I-SPY (Investigation of Serial Studies to Predict Your Therapeutic
Response with Imaging And moLecular Analysis) TRIAL is conducted by a
consortium that brings together the U.S. Food and Drug Administration
(FDA), leading academic medical centers, and patient advocates, as well
as Merck and other pharmaceutical and biotech companies.

The I-SPY 2 TRIAL is a collaborative effort among academic investigators
from 20 major cancer research centers across the U.S. and QuantumLeap
Healthcare Collaborative, the FDA, and the Foundation for the National
Institutes of Health (FNIH) Cancer Biomarkers Consortium. Major
supporters include The Safeway Foundation and the Bill Bowes Foundation.

The I-SPY 2 TRIAL’s adaptive statistical design was developed by the
pioneering principal investigators for the I-SPY trial, Laura J.
Esserman, M.D., MBA, and Donald A. Berry, Ph.D., professor of
biostatistics at The University of Texas MD Anderson Cancer Center and
founder of Berry Consultants in collaboration with the FDA, industry,
and many leading academic collaborators including the Agents working
group chair (Doug Yee, M.D. from the University of Minnesota) and the
Trial Operations working group chair (Angie DeMichele, M.D. from the
University of Pennsylvania). The trial is a unique collaborative effort
where over 50 clinicians are actively engaged in the conduct of the
trial.

The I-SPY 2 TRIAL adaptive-trial design is based on Bayesian predictive
probability that a biological regimen will be shown to be statistically
superior to standard therapy in an equally randomized 300-patient
confirmatory trial. Regimens that have a high Bayesian predictive
probability of showing superiority in at least one of 10 predefined
signatures graduate from the trial. Regimens are dropped for futility if
they show a low predictive probability of showing superiority over
standard therapy in all 10 signatures. A maximum total of 120 patients
can be assigned to each experimental regimen. A regimen can graduate
early and at any time after having 60 patients assigned to it.

About KEYTRUDA

^®

(pembrolizumab) Injection

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of
the body’s immune system to help detect and fight tumor cells. KEYTRUDA
is a humanized monoclonal antibody that 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.

Studies of KEYTRUDA – from the largest immuno-oncology program in the
industry with more than 500 trials – include a wide variety of cancers
and treatment settings. The KEYTRUDA clinical program seeks to
understand factors that predict a patient’s likelihood of benefitting
from treatment with KEYTRUDA, including the exploration of several
different biomarkers across a broad range of tumors.

KEYTRUDA (pembrolizumab) is administered as an intravenous infusion over
30 minutes every three weeks for the approved indications. KEYTRUDA for
injection is supplied in a 100 mg single-dose vial.

KEYTRUDA (pembrolizumab) Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic melanoma at a fixed dose of 200 mg every three weeks until
disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA, as a single agent, is indicated for the first-line treatment
of patients with metastatic non-small cell lung cancer (NSCLC) whose
tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as
determined by an FDA-approved test, with no EGFR or ALK genomic tumor
aberrations.

KEYTRUDA, as a single agent, is also indicated for the treatment of
patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) 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.

KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated
for the first-line treatment of patients with metastatic nonsquamous
NSCLC. This indication is approved under accelerated approval based on
tumor response rate and progression-free survival. Continued approval
for this indication may be contingent upon verification and description
of clinical benefit in the confirmatory trials.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg
every three weeks until disease progression, unacceptable toxicity, or
up to 24 months in patients without disease progression.

When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA
should be administered prior to chemotherapy when given on the same day.
See also the Prescribing Information for pemetrexed and carboplatin.

Head and Neck Cancer

KEYTRUDA (pembrolizumab) is indicated for the treatment of patients with
recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)
with disease progression on or after platinum-containing chemotherapy.
This indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is
administered at a fixed dose of 200 mg every three weeks until disease
progression, unacceptable toxicity, or up to 24 months in patients
without disease progression.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients
with refractory classical Hodgkin lymphoma (cHL), or who have relapsed
after three or more prior lines of therapy. This indication is approved
under accelerated approval based on tumor response rate and durability
of response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials. In adults with cHL, KEYTRUDA is administered at a
fixed dose of 200 mg every three weeks until disease progression or
unacceptable toxicity, or up to 24 months in patients without disease
progression. In pediatric patients with cHL, KEYTRUDA is administered at
a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until
disease progression or unacceptable toxicity, or up to 24 months in
patients without disease progression.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma who are not eligible for
cisplatin-containing chemotherapy. This indication is approved under
accelerated approval based on tumor response rate and duration of
response. Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the confirmatory
trials.

KEYTRUDA is also indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma who have disease progression
during or following platinum-containing chemotherapy or within 12 months
of neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy.

In locally advanced or metastatic urothelial carcinoma, KEYTRUDA is
administered at a fixed dose of 200 mg every three weeks until disease
progression or unacceptable toxicity, or up to 24 months in patients
without disease progression.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA (pembrolizumab) is indicated for the treatment of adult and
pediatric patients with unresectable or metastatic microsatellite
instability-high (MSI-H) or mismatch repair deficient (dMMR)

• solid tumors that have progressed following prior treatment and who
  have no satisfactory alternative treatment options, or
• colorectal cancer that has progressed following treatment with
  fluoropyrimidine, oxaliplatin, and irinotecan.

This indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials. The safety and
effectiveness of KEYTRUDA in pediatric patients with MSI-H central
nervous system cancers have not been established.

In adult patients with MSI-H cancer, KEYTRUDA is administered at a fixed
dose of 200 mg every three weeks until disease progression, unacceptable
toxicity, or up to 24 months in patients without disease progression. In
pediatric patients with MSI-H cancer, KEYTRUDA is administered at a dose
of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease
progression or unacceptable toxicity, or up to 24 months in patients
without disease progression.

Selected Important Safety Information for KEYTRUDA

^®
 (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases.
Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA,
including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%)
pneumonitis, and occurred more frequently in patients with a history of
prior thoracic radiation (6.9%) compared to those without (2.9%).
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.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48
(1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 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 for Grade 2 or 3; permanently discontinue KEYTRUDA for
Grade 4 colitis.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19
(0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3
(0.4%), 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.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of
2799 patients receiving KEYTRUDA (pembrolizumab), including Grade 2
(0.2%), 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.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism,
hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%)
of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3
(0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799
patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%)
hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients
receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. 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.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic
ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients.
Monitor patients for hyperglycemia or other signs and symptoms of
diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA
and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9
(0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3
(0.1%), 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.

KEYTRUDA can cause other clinically important immune-mediated adverse
reactions. These immune-mediated reactions may occur in any organ
system. 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 2799 patients:
arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash
(1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis,
vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising
in a patient with inflammatory foci in brain parenchyma. In addition,
myelitis and myocarditis were reported in other clinical trials,
including classical Hodgkin lymphoma, and postmarketing use.

Solid organ transplant rejection has been reported in postmarketing use
of KEYTRUDA (pembrolizumab). Treatment with KEYTRUDA may increase the
risk of rejection in solid organ transplant recipients. Consider the
benefit of treatment with KEYTRUDA vs the risk of possible organ
rejection in these patients.

KEYTRUDA can cause severe or life-threatening infusion-related
reactions, including hypersensitivity and anaphylaxis, which have been
reported in 6 (0.2%) of 2799 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.

Immune-mediated complications, including fatal events, occurred in
patients who underwent allogeneic hematopoietic stem cell
transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients
with cHL who proceeded to allogeneic HSCT after treatment with KEYTRUDA
on any trial, 6 patients (26%) developed graft-versus-host-disease
(GVHD), one of which was fatal, and 2 patients (9%) developed severe
hepatic veno-occlusive disease (VOD) after reduced-intensity
conditioning, one of which was fatal. Cases of fatal hyperacute GVHD
after allogeneic HSCT have also been reported in patients with lymphoma
who received a PD-1 receptor–blocking antibody before transplantation.
These complications may occur despite intervening therapy between PD-1
blockade and allogeneic HSCT. Follow patients closely for early evidence
of transplant-related complications such as hyperacute GVHD, severe
(Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic
VOD, and other immune-mediated adverse reactions, and intervene promptly.

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 KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9%
of 555 patients with advanced melanoma; 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 (pembrolizumab)
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 KEYNOTE-002, KEYTRUDA was discontinued due to adverse reactions in
12% of 357 patients with advanced melanoma; 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 maculopapular 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.

KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of
682 patients with metastatic NSCLC. The most common adverse event
resulting in permanent discontinuation of KEYTRUDA was pneumonitis
(1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred
in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue
(1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased
appetite (1.3%), and pneumonitis (1%). The most common adverse reactions
(occurring in at least 20% of patients and at a higher incidence than
with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs
20%), and nausea (20% vs 18%).

When KEYTRUDA was administered in combination with carboplatin and
pemetrexed (carbo/pem), KEYTRUDA was discontinued in 10% of 59 patients.
The most common adverse reaction resulting in discontinuation of
KEYTRUDA (≥2%) was acute kidney injury (3.4%). Adverse reactions leading
to interruption of KEYTRUDA occurred in 39% of patients; the most common
(≥2%) were fatigue (8%), neutrophil count decreased (8%), anemia (5%),
dyspnea (3.4%), and pneumonitis (3.4%).The most common adverse reactions
(≥20%) with KEYTRUDA compared to carbo/pem alone were fatigue (71% vs
50%), nausea (68% vs 56%), constipation (51% vs 37%), rash (42% vs 21%),
vomiting (39% vs 27%), dyspnea (39% vs 21%), diarrhea (37% vs 23%),
decreased appetite (31% vs 23%), headache (31% vs 16%), cough (24% vs
18%), dizziness (24% vs 16%), insomnia (24% vs 15%), pruritus (24% vs
4.8%), peripheral edema (22% vs 18%), dysgeusia (20% vs 11%), alopecia
(20% vs 3.2%), upper respiratory tract infection (20% vs 3.2%), and
arthralgia (15% vs 24%). This study was not designed to demonstrate a
statistically significant difference in adverse reaction rates for
KEYTRUDA (pembrolizumab) as compared to carbo/pem alone for any
specified adverse reaction.

KEYTRUDA was discontinued due to adverse reactions in 17% of 192
patients with HNSCC. Serious adverse reactions occurred in 45% of
patients. The most frequent serious adverse reactions reported in at
least 2% of patients were pneumonia, dyspnea, confusional state,
vomiting, pleural effusion, and respiratory failure. The most common
adverse reactions (reported in at least 20% of patients) were fatigue,
decreased appetite, and dyspnea. Adverse reactions occurring in patients
with HNSCC were generally similar to those occurring in patients with
melanoma or NSCLC, with the exception of increased incidences of facial
edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening
hypothyroidism.

KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients
with cHL, and treatment was interrupted due to adverse reactions in 26%
of patients. Fifteen percent (15%) of patients had an adverse reaction
requiring systemic corticosteroid therapy. Serious adverse reactions
occurred in 16% of patients. The most frequent serious adverse reactions
(≥1%) included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and
herpes zoster. Two patients died from causes other than disease
progression; one from GVHD after subsequent allogeneic HSCT and one from
septic shock. The most common adverse reactions (occurring in ≥20% of
patients) were fatigue (26%), pyrexia (24%), cough (24%),
musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in
11% of 370 patients with locally advanced or metastatic urothelial
carcinoma. The most common adverse reactions (in ≥20% of patients) were
fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%),
constipation (21%), rash (21%), and diarrhea (20%). Eighteen patients
(5%) died from causes other than disease progression. Five patients
(1.4%) who were treated with KEYTRUDA experienced sepsis which led to
death, and 3 patients (0.8%) experienced pneumonia which led to death.
Adverse reactions leading to interruption of KEYTRUDA occurred in 22% of
patients; the most common (≥1%) were liver enzyme increase, diarrhea,
urinary tract infection, acute kidney injury, fatigue, joint pain, and
pneumonia. Serious adverse reactions occurred in 42% of patients, the
most frequent (≥2%) of which were urinary tract infection, hematuria,
acute kidney injury, pneumonia, and urosepsis.

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8%
of 266 patients with locally advanced or metastatic urothelial
carcinoma. The most common adverse reaction resulting in permanent
discontinuation of KEYTRUDA was pneumonitis (1.9%). Adverse reactions
leading to interruption of KEYTRUDA occurred in 20% of patients; the
most common (≥1%) were urinary tract infection (1.5%), diarrhea (1.5%),
and colitis (1.1%). The most common adverse reactions (≥20%) in patients
who received KEYTRUDA vs those who received chemotherapy were fatigue
(38% vs 56%), musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%),
decreased appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs
13%). Serious adverse reactions occurred in 39% of KEYTRUDA
(pembrolizumab)-treated patients, the most frequent (≥2%) of which were
urinary tract infection, pneumonia, anemia, and pneumonitis.

The most common adverse reactions (reported in ≥20% of patients) were
fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough,
dyspnea, musculoskeletal pain, constipation, and nausea.

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.

About QuantumLeap Healthcare Collaborative

QuantumLeap Healthcare Collaborative, a non-profit foundation, was
established in 2005 as a collaboration between medical researchers at
University of California at San Francisco, and Silicon Valley
entrepreneurs. QuantumLeap’s mission is to accelerate transfer of
high-impact research in clinical processes and systems technology into
widespread adoption so that patients and physicians can benefit from the
research as soon as practicable. QuantumLeap provides operational,
financial and regulatory oversight to I-SPY. For more information,
visit: http://www.quantumleaphealth.org.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology
medicines to help people with cancer worldwide. At Merck, 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 500 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 more than a century, Merck, a leading global biopharmaceutical
company known as MSD outside of the United States and Canada, has been
inventing for life, bringing forward medicines and vaccines for many of
the world’s most challenging diseases. 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. Today, Merck continues to be at the forefront of
research to advance the prevention and treatment of diseases that
threaten people and communities around the world – including cancer,
cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease
and infectious diseases including HIV and Ebola. For more information,
visit www.merck.com
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Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

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
and expectations of the company’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 health care legislation in the
United States and internationally; global trends toward health care cost
containment; technological advances, new products and patents attained
by competitors; challenges inherent in new product development,
including obtaining regulatory approval; the company’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 the company’s patents
and other protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory actions.

The company 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 the company’s 2016 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).

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

.

Media:
Merck
Pamela Eisele, 267-305-3558
or
Merck
Ann Bush, 908-740-6677
or
King + Company for QuantumLeap
Caren Browning, 212-561-7464
or
Investors:
Teri Loxam, 908-740-1986
or
Amy Klug, 908-740-1898