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News breaking: 2017-09-08

Merck’s KEYTRUDA® (pembrolizumab) Plus Pemetrexed and Carboplatin..


Merck’s KEYTRUDA® (pembrolizumab) Plus Pemetrexed and Carboplatin (pem/carbo) Demonstrated Continued Benefit in Overall Response Rates and Progression-Free Survival Compared to Pem/Carbo Alone in Patients with First-Line Nonsquamous NSCLC
Five Months of Additional Data from KEYNOTE-021, Cohort G, Including Updated Overall Survival, to be Presented at ESMO 2017 Congress
Category:
Corporate News, Latest News, Oncology Newsroom, Prescription Medicine News
Friday, September 8, 2017 10:33 am EDT
Dateline:
KENILWORTH, N.J.
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Public Company Information:
NYSE:MRK
"Lung cancer is one of the most common and devastating cancers, and these additional data confirm that KEYTRUDA in combination with pemetrexed and carboplatin has the potential to have a meaningful impact in the lives of many of these patients"
KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced updated results from Cohort G of the phase 2 KEYNOTE-021
trial investigating KEYTRUDA® (pembrolizumab), the company’s
anti-PD-1 therapy, in combination with pemetrexed and carboplatin
(pem/carbo) in patients with previously untreated advanced nonsquamous
non-small cell lung cancer (NSCLC), with or without PD-L1 expression.
With an additional five months of follow-up, significant improvements
observed in prior analyses were maintained, including improvements in
overall response rate (ORR) and progression-free survival (PFS) for
KEYTRUDA + pem/carbo compared to pem/carbo alone. With a median of 18.7
months of follow-up, more than half of patients in the KEYTRUDA
combination arm responded to treatment compared to approximately
one-third in the pem/carbo arm (ORR of 56.7% vs. 31.7% [95% CI,
7.2-40.9], p=0.0029). The risk of progression or death continued to be
reduced by nearly half with KEYTRUDA + pem/carbo compared to pem/carbo
alone (HR 0.54 [95% CI, 0.33-0.88, p=0.0067]). In addition, despite the
crossover design, a trend in improvement in overall survival continues
to be seen for KEYTRUDA + pem/carbo compared to pem/carbo alone (HR,
0.59 [95% CI, 0.34-1.05, p=0.03]). Findings are being presented at the
European Society for Medical Oncology (ESMO) 2017 Congress in Madrid,
Spain, in an oral presentation on Friday, Sept. 8 from 5:03 – 5:15 p.m.
CEST (Location: Madrid Auditorium) (Abstract #LBA49).
“The continued benefit observed with KEYTRUDA plus pem/carbo in overall
response rate and progression-free survival reinforce the importance of
this combination therapy for the treatment of patients with advanced
nonsquamous non-small cell lung cancer, with or without PD-L1
expression,” said Dr. Hossein Borghaei, chief of the division
of thoracic medical oncology, Fox Chase Cancer Center.
“Lung cancer is one of the most common and devastating cancers, and
these additional data confirm that KEYTRUDA in combination with
pemetrexed and carboplatin has the potential to have a meaningful impact
in the lives of many of these patients,” said Dr. Roger Dansey, senior
vice president and therapeutic area head, oncology late-stage
development, Merck Research Laboratories.
Merck is currently advancing multiple registration-enabling studies in
NSCLC with KEYTRUDA (pembrolizumab) as monotherapy and in combination,
including the combination of KEYTRUDA plus a platinum/pemetrexed-based
chemotherapy regimen in patients with previously untreated nonsquamous
NSCLC in the ongoing phase 3 KEYNOTE-189 trial.
Data from KEYNOTE-021, Cohort G (Abstract #LBA49)
KEYNOTE-021, Cohort G, evaluated the efficacy and safety of KEYTRUDA +
pem/carbo compared to pem/carbo in 123 patients with metastatic,
nonsquamous, EGFR- and ALK-negative NSCLC in the first-line treatment
setting. In patients randomized to the pem/carbo arm, 63 percent
(n=40/63) went on to receive subsequent anti-PD-1 or PD-L1 therapy,
including 25 who received KEYTRUDA as part of study crossover
(additional details on the trial design are provided below).
Data to be presented at ESMO include five months of additional follow-up
from prior presentations, for a median follow-up of 18.7 months (range:
0.8-29.0). In this analysis, the KEYTRUDA + pem/carbo combination group
(n=60) continued to show improvement over the group receiving pem/carbo
alone (n=63) in overall response rate, duration of response and PFS.
ORR was 56.7 percent in the KEYTRUDA + pem/carbo combination group
compared to 31.7 percent in the pem/carbo group (95% CI, 7.2-40.9;
p=0.0029). The median duration of response had not been reached in
either arm (range: 1.4+ to 22.7+ with KEYTRUDA + pem/carbo and 2.8 to
23.7+ in the pem/carbo group). At the time of analysis, 50 percent of
responses were ongoing in the KEYTRUDA + pem/carbo combination group
compared to 40 percent in the pem/carbo group.
The patients in the KEYTRUDA + pem/carbo arm had a 46 percent reduction
in progression or death risk compared with pem/carbo alone (HR 0.54 [95%
CI, 0.33-0.88, p=0.0067]). The median PFS was twice as long in the group
receiving KEYTRUDA, with 19.0 months (95% CI, 8.5-not reached) for
KEYTRUDA plus pem/carbo compared to 8.9 months in the pem/carbo group
(95% CI, 6.2-11.8). At 12 and 18 months, PFS in the KEYTRUDA + pem/carbo
combination group was 57 percent and 52 percent, respectively, compared
to 37 percent and 29 percent in the pem/carbo group.
A trend toward improvement in OS was observed in the KEYTRUDA
(pembrolizumab) + pem/carbo arm: the combination was associated with a
41 percent reduction in the risk of death (HR, 0.59 [95% CI, 0.34-1.05,
p=0.03]). The median OS was not reached (range: 22.8-not reached) in the
KEYTRUDA + pem/carbo combination group compared to 20.9 months (range:
14.9-not reached) in the pem/carbo group.
The safety findings were consistent with previously presented results
from this study. Grade 3-5 treatment-related adverse events (TRAEs)
occurred in 41 percent of patients in the KEYTRUDA + pem/carbo group.
TRAEs of any grade with an incidence of 15 percent or more in the
KEYTRUDA + pem/carbo group were fatigue (68%), nausea (59%), anemia
(34%), vomiting (31%), rash (27%), diarrhea (24%), decreased appetite
(22%), AST increased (19%), constipation (19%), dysgeusia (19%), ALT
increased (17%), blood creatinine increased (17%), decreased neutrophils
(17%) and lacrimation increased (15%). The most common immune-mediated
adverse events of any grade in patients receiving KEYTRUDA + pem/carbo
were hypothyroidism (14%), hyperthyroidism (8%), pneumonitis (7%),
infusion reactions (2%), severe skin toxicity (2%) and colitis (2%).
There was one treatment-related death in a patient receiving KEYTRUDA +
pem/carbo and two in patients receiving pem/carbo alone.
About KEYNOTE-021, Cohort G
Cohort G1 of the multicenter, open-label, phase 1/2 multi-cohort
KEYNOTE-021 study evaluated the efficacy and safety of KEYTRUDA in
combination with pemetrexed and carboplatin (KEYTRUDA + pem/carbo)
compared with pemetrexed and carboplatin (pem/carbo) in 123 patients
with metastatic, nonsquamous, EGFR- and ALK-negative NSCLC in the
first-line treatment setting. The KEYNOTE-021G1 trial was conducted in
collaboration with Eli Lilly and Company, the maker of pemetrexed.
Patients were randomized to receive KEYTRUDA + pem/carbo (n=60) or
pem/carbo alone (n=63). Patients in the KEYTRUDA + pem/carbo combination
group received KEYTRUDA (200 mg), pemetrexed (500 mg/m2) and
carboplatin (AUC 5 mg/mL/min) every three weeks for four cycles followed
by KEYTRUDA every three weeks. In the pem/carbo group, patients received
pemetrexed (500 mg/m2) and carboplatin (AUC 5 mg/mL/min)
alone for four cycles. At the investigator’s discretion, maintenance
pemetrexed (500 mg/m2) every three weeks was permitted in
both treatment groups. The major efficacy outcome measure was ORR as
assessed by blinded independent central review (BICR) using Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Additional
efficacy outcome measures were PFS as assessed by BICR using RECIST 1.1,
duration of response and OS.
About Lung Cancer
Lung cancer, which forms in the tissues of the lungs, usually within
cells lining the air passages, is the leading cause of cancer death
worldwide. Each year, more people die of lung cancer than die of colon,
breast and prostate cancers combined. The two main types of lung cancer
are non-small cell and small cell. NSCLC is the most common type of lung
cancer, accounting for about 85 percent of all cases. The five-year
survival rate for patients suffering from highly advanced, metastatic
(Stage IV) lung cancers is estimated to be two percent.
About KEYTRUDA

®

(pembrolizumab) Injection
100 mg
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
(pembrolizumab).
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 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 (pembrolizumab) 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 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 (pembrolizumab) 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 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
(pembrolizumab). 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 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 (pembrolizumab) 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 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:
Media:Pamela Eisele, 267-305-3558orTeresa Mueller, 908-740-1884orInvestors:Teri Loxam, 908-740-1986orAmy Klug, 908-740-1898
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