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News breaking: 2017-09-11

Merck Announces Findings from Phase 3 Study of KEYTRUDA® (pembroliz..


Merck Announces Findings from Phase 3 Study of KEYTRUDA® (pembrolizumab), Compared to Standard of Care, in Patients with Previously Treated Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
First Presentation of KEYNOTE-040 Results at ESMO 2017 Congress
Category:
Corporate News, Latest News, Oncology Newsroom, Prescription Medicine News
Monday, September 11, 2017 9:00 am EDT
Dateline:
KENILWORTH, N.J.
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Public Company Information:
NYSE:MRK
"These data, including progression-free survival and overall response rate, show the activity and efficacy of pembrolizumab in this disease, and are consistent with prior studies of pembrolizumab in recurrent head and neck squamous cell carcinoma"
KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced results of the phase 3 KEYNOTE-040 trial investigating
KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy,
compared to standard treatment (methotrexate, docetaxel or cetuximab) in
patients with recurrent or metastatic head and neck squamous cell
carcinoma (HNSCC) with disease progression on or after
platinum-containing chemotherapy. As previously disclosed, the study did
not meet its pre-specified primary endpoint of overall survival (OS).
The findings include updated survival data showing a 19 percent
reduction in the risk of death over standard treatment in the
intent-to-treat population (HR, 0.81 [95% CI, 0.66-0.99]; one sided p =
0.0204), with pre-specified p-value required for statistical
significance of 0.0175, and a median OS of 8.4 months with KEYTRUDA (95%
CI, 6.5-9.4) compared to 7.1 months with standard treatment (95% CI,
5.9-8.1). Complete results will be presented for the first time at the
European Society for Medical Oncology (ESMO) 2017 Congress in Madrid,
Spain, in an oral presentation today from 3:00 – 3:12 p.m. CEST
(Location: Granada Auditorium) (Abstract #LBA45_PR).
“These data, including progression-free survival and overall response
rate, show the activity and efficacy of pembrolizumab in this disease,
and are consistent with prior studies of pembrolizumab in recurrent head
and neck squamous cell carcinoma,” said Ezra Cohen, M.D., associate
director for translational science, Moores Cancer Center and co-director
of the San Diego Center for Precision Immunotherapy, University of
California, San Diego. “KEYNOTE-40 strengthens the rationale for further
studies, and expansion into earlier lines of disease.”
With more than 20 trials, Merck currently has the largest
immuno-oncology clinical development program in head and neck cancer and
is advancing multiple registration-enabling studies investigating
KEYTRUDA (pembrolizumab) as monotherapy and in combination with other
cancer treatments – including KEYNOTE-048 and KEYNOTE-412.
“Although the primary efficacy analysis did not show a statistically
significant improvement in overall survival, these data add to the
evolving science for KEYTRUDA in head and neck cancer,” said Dr. Jon
Cheng, associate vice president, Merck Research Laboratories.
Data in Second-Line Treatment Setting, KEYNOTE-040 (Abstract
#LBA45_PR)
KEYNOTE-040 is a randomized, multi-center, phase 3 study investigating
KEYTRUDA as a monotherapy (n=247) versus standard treatment
(methotrexate, docetaxel or cetuximab) (n=248) in patients with
recurrent or metastatic HNSCC (additional details on the trial design
are provided below).
Data presented at ESMO are based on findings in the intent-to-treat
population (n=495) and include analysis of efficacy endpoints based on
PD-L1 expression using two measurements: PD-L1 CPS ≥1 (n=387) and PD-L1
TPS ≥50% (n=129). More than a third of patients in the intent-to-treat
population went on to receive subsequent therapy, including 11 of 84
patients in the KEYTRUDA arm and 31 of 100 patients in the standard
treatment arm who received subsequent treatment with an immune
checkpoint inhibitor. Other subsequent treatments included chemotherapy,
EGFR inhibitor, kinase inhibitor, other immunotherapy, and other
treatments.
Data show that in the intent-to-treat population, the median OS was 8.4
months with KEYTRUDA (95% CI, 6.5-9.4) compared to 7.1 months with
standard treatment (95% CI, 5.9-8.1) (HR, 0.81 [95% CI, 0.66-0.99]; one
sided p = 0.0204); the 12-month OS rate was 37.3 percent with KEYTRUDA
compared to 27.2 percent with standard treatment. Further analysis of
the primary endpoint based on PD-L1 expression showed:
In patients with PD-L1 CPS ≥1, the median OS was 8.7 months with
KEYTRUDA (95% CI, 6.9-11.4) and 7.1 months with standard treatment
(95% CI, 5.7-8.6) (HR, 0.75 [95% CI, 0.59-0.95]; p = 0.0078); the
12-month OS rate was 40.1 percent with KEYTRUDA compared to 26.7
percent with standard treatment.
In patients with PD-L1 TPS ≥50%, the median OS was 11.6 months with
KEYTRUDA (95% CI, 8.3-19.5) and 7.9 months with standard treatment
(95% CI, 4.8-9.3) (HR, 0.54 [95% CI, 0.35-0.82]; p = 0.0017); the
12-month OS rate was 46.6 percent with KEYTRUDA compared to 25.8
percent with standard treatment.
The overall response rate (ORR) in the intent-to-treat population was
14.6 percent in the KEYTRUDA (pembrolizumab) arm compared to 10.1
percent in the standard treatment arm (p = 0.0610). In patients with
PD-L1 CPS ≥1, the ORR was 17.3 percent with KEYTRUDA compared to 9.9
percent with standard treatment (p = 0.0171). In patients with PD-L1 TPS
≥50%, the ORR was 26.6 percent with KEYTRUDA compared to 9.2 percent
with standard treatment (p = 0.0009).
The median progression-free survival (PFS) was 2.1 months in the
intent-to-treat population with KEYTRUDA (95% CI, 2.1-2.3) and 2.3
months with standard treatment (95% CI, 2.1-2.8) (HR, 0.95 [95% CI,
0.79-1.16]; p = 0.3037). In patients with PD-L1 CPS ≥1, the median PFS
was 2.2 months with KEYTRUDA (95% CI, 2.1-3.0) and 2.3 months with
standard treatment (95% CI, 2.1-3.3) (HR, 0.89 [95% CI, 0.72-1.11]; p =
0.1526). In patients with PD-L1 TPS ≥50%, the median PFS was 3.5 months
with KEYTRUDA (95% CI, 2.1-6.3) and 2.2 months with standard treatment
(95% CI, 2.0-2.5) (HR, 0.58 [95% CI, 0.39-0.87]; p = 0.0034).
The safety profile of KEYTRUDA was consistent with that observed in
previously reported studies. Treatment-related adverse events (TRAEs) of
any grade occurred in 155 patients (63.0%) in the KEYTRUDA arm and 196
patients (83.8%) in the standard treatment arm. Across any arm, TRAEs
with incidence of 10 percent or more included hypothyroidism, fatigue,
diarrhea, rash, asthenia, anemia, nausea, mucosal inflammation,
stomatitis, decreased neutrophil count and alopecia. Immune-mediated
adverse events, any grade, occurring in the KEYTRUDA arm were
hypothyroidism, pneumonitis, infusion reactions, severe skin reactions,
hyperthyroidism, colitis, Guillain-Barre syndrome and hepatitis.
Discontinuation due to TRAEs occurred in 15 patients (6.1%) in the
KEYTRUDA arm and 12 patients (5.1%) in the standard treatment arm.
Deaths due to treatment-related adverse events occurred in four patients
(1.6%) in the KEYTRUDA arm and two patients (0.9%) in the standard
treatment arm.
About KEYNOTE-040
KEYNOTE-040 is a randomized, multi-center, pivotal phase 3 study
investigating KEYTRUDA as a monotherapy versus standard treatment
(methotrexate, docetaxel or cetuximab) for the treatment of recurrent or
metastatic HNSCC. The primary endpoint is OS; secondary endpoints
include PFS and ORR. The study, which opened in November 2014, enrolled
495 patients to receive KEYTRUDA (200 mg fixed dose every three weeks)
or investigator-choice chemotherapy (methotrexate [40 mg/m2
on Days 1, 8, and 15 of each 3-week cycle], docetaxel [75 mg/m2
on Day 1 of each 3-week cycle], or cetuximab [400 mg/m2
loading dose on Day 1 and 250 mg/m2 IV on Days 8 and 15 of
Cycle 1], followed by cetuximab [250 mg/m2 on Days 1, 8, and
15 of each subsequent 3-week cycle]). Patients enrolled in the study had
been previously treated with one to two platinum-containing systemic
regimens.
About KEYTRUDA

®

(pembrolizumab) Injection
100mg
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 550 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) 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 (pembrolizumab) 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 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 (pembrolizumab) 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 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
(pembrolizumab) 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, 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. The incidence of new or worsening hypothyroidism was
higher in patients with HNSCC, occurring in 28 (15%) of 192 patients
with HNSCC, including Grade 3 (0.5%) 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.
Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic
epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative
dermatitis, and bullous pemphigoid can occur. Monitor patients for
suspected severe skin reactions and based on the severity of the adverse
reaction, withhold or permanently discontinue KEYTRUDA (pembrolizumab)
and administer corticosteroids. For signs and symptoms of SJS or TEN,
withhold KEYTRUDA and refer the patient for specialized care for
assessment and treatment. If SJS or TEN is confirmed, permanently
discontinue KEYTRUDA.
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%), 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. 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
(pembrolizumab) 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 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.
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 (pembrolizumab) 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 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 (pembrolizumab)
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-treated
patients, the most frequent (≥2%) of which were urinary tract infection,
pneumonia, anemia, and pneumonitis.
There is limited experience in pediatric patients. Efficacy for
pediatric patients was extrapolated from the results in the adult cHL
population. In a study of 40 pediatric patients with advanced melanoma,
PD-L1–positive advanced, relapsed, or refractory solid tumors or
lymphoma, patients were treated with KEYTRUDA for a median of 43 days
(range 1-414 days), with 24 patients (60%) receiving treatment for 42
days or more. The safety profile in pediatric patients was similar to
that seen in adults treated with KEYTRUDA. Toxicities that occurred at a
higher rate (≥15% difference) in these patients when compared to adults
under 65 years of age were fatigue (45%), vomiting (38%), abdominal pain
(28%), hypertransaminasemia (28%), and hyponatremia (18%).
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.
Our 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 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

and connect with us on Twitter, Facebook, Instagram,
YouTube
and LinkedIn.
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

.
Contact:
MerckMedia:Pamela Eisele, 267-305-3558Elizabeth Sell, 267-305-3877orInvestors:Teri Loxam, 908-740-1986Amy Klug, 908-740-1898
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