First Presentation of KEYNOTE-040 Results at
ESMO 2017 Congress
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.
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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 andPatient
Information/Medication Guide for KEYTRUDA
at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20170911005592/en/
MerckMedia:Pamela Eisele, 267-305-3558Elizabeth Sell,
267-305-3877orInvestors:Teri Loxam, 908-740-1986Amy Klug,
908-740-1898
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