New KEYTRUDA® (pembrolizumab) Data in Advanced Urothelial Cancer Demonstrate Overall Response Rate of 24 Percent in Cisplatin-Ineligible Patients
October 8, 2016 1:15 am ET
Results from Interim Analysis of Phase 2 KEYNOTE-052 Study to be Presented at ESMO 2016 Congress and Highlighted in ESMO Press Program
First Presentation of Data Investigating KEYTRUDA in the Front Line Treatment of Bladder Cancer
KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced positive findings from the phase 2 KEYNOTE-052 study
investigating the use of KEYTRUDA® (pembrolizumab), the
company’s anti-PD-1 therapy, in previously untreated patients with
unresectable (inoperable) or metastatic urothelial cancer who are
ineligible for cisplatin-based therapy. Data presented at the ESMO 2016
Congress, the annual meeting of the European Society for Medical
Oncology, showed an overall response rate (ORR) of 24 percent (n=24/100)
(95% CI, 16-34) in the total study population, which included patients
with and without PD-L1 expression.
“We have a growing body of evidence of KEYTRUDA’s activity in a range of
cancers and treatment settings including the first-line treatment of
patients with advanced urothelial cancer who will not tolerate
cisplatin-based therapy,” said Dr. Roger Dansey, senior vice president,
oncology late-stage development, Merck Research Laboratories.
The KEYTRUDA clinical development program includes more than 30 tumor
types in more than 350 clinical studies, including more than 100 trials
that combine KEYTRUDA with other cancer treatments. Merck has the
largest immuno-oncology clinical development program in bladder cancer
with 27 trials involving KEYTRUDA, including four registration-enabling
studies currently underway.
“There have been very few advancements in the treatment of bladder
cancer in the past several decades, and patients with urothelial cancer
who are ineligible for cisplatin-based therapy are in significant need
of new approaches to care,” said Dr. Dean F. Bajorin, study investigator
and medical oncologist at Memorial Sloan Kettering Cancer Center. “These
data are exciting and demonstrate the potential for an anti-PD-1
therapy, such as pembrolizumab, to address the unmet treatment need that
exists today for cisplatin-ineligible patients with this type of
Findings from KEYNOTE-052 are being presented at the ESMO 2016 Congress
by Dr. Arjun V. Balar, medical oncologist and assistant professor of
medicine at the Perlmutter Cancer Center at NYU Langone Medical Center,
on Oct. 8 from 9:30 – 9:45 a.m. CEST (Abstract: # LBA32_PR) and are
featured in the official ESMO press program.
Additional Findings from KEYNOTE-052
KEYNOTE-052 is an open-label, phase 2 study evaluating KEYTRUDA
(pembrolizumab) (200 mg every three weeks) monotherapy as a first-line
treatment in an estimated 350 patients with unresectable (inoperable) or
metastatic urothelial cancer (a type of bladder cancer) who are
ineligible for cisplatin-based therapy. The primary endpoints include
ORR in all patients enrolled in the study (total study population) and
in patients with PD-L1 positive tumors (expression of one percent or
more). Secondary endpoints include duration of response,
progression-free survival (PFS), and overall survival (OS). Tumor
response was measured according to RECIST (Response Evaluation Criteria
in Solid Tumors) v1.1 as assessed by blinded independent central review.
Findings presented at the ESMO 2016 Congress are from the planned
interim analysis of the first 100 patients, which was intended to
evaluate ORR and determine the PD-L1-high expression cut-point as
examined by expression in tumor and immune cells. Forty-five percent of
patients (n=45/100) had an ECOG (Eastern Cooperative Oncology Group)
Performance Status (PS) score of two, 30 percent (n=30/100) had a PS
score of one, and 24 percent (n=24/100) had a PS score of zero.
In the total study population, ORR was 24 percent (n=24/100) (95% CI,
16-34) with a complete response rate of six percent (n=6/100) (95% CI,
2-13). Review of the outcomes based on PD-L1 expression showed that in
patients with PD-L1 expression of less than one percent, ORR was 18
percent (n=6/33) (95% CI, 7-36) with a complete response rate of three
percent (n=1/33) (95% CI, 0.1-16); in patients with PD-L1 expression
greater than or equal to one percent and less than 10 percent, ORR was
15 percent (n=5/33) (95% CI, 5-32) with no complete responses; and, in
patients expressing PD-L1 at levels equal to or greater than 10 percent,
ORR was 37 percent (n=11/30) (95% CI, 20-56) with a complete response
rate of 13 percent (n=4/30) (95% CI, 4-31). Among the 24 percent of
patients in the total study population who were responding to treatment,
the median duration of response had not been reached (range 1.4+ to 9.8+
months), with 83 percent of patients (n=20/24) having responses of six
months or longer.
The safety profile of KEYTRUDA (pembrolizumab) was consistent with that
observed in previously reported KEYTRUDA studies. The treatment-related
adverse events observed in this trial (any grade occurring in five
percent or more of patients) were fatigue (n=14), pruritus (n=12),
pyrexia (n=8), decreased appetite (n=7), diarrhea (n=7), rash (n=7),
chills (n=6), hypothyroidism (n=6), and nausea (n=6). Grade 3-4
treatment-related adverse events observed (occurring in 2 or more
patients) were fatigue (n=4), muscle spasms (n=2), decreased appetite
(n=1), and diarrhea (n=1). Immune-mediated adverse events of Grade 3-4
were nephritis (n=1) and pneumonitis (n=2). Five patients discontinued
due to a treatment-related adverse event; there were no
About Bladder Cancer
Bladder cancer begins when cells in the urinary bladder start to grow
uncontrollably. As more cancer cells develop, they can form a tumor and
spread to other areas of the body. Urothelial carcinoma, the most common
type of bladder cancer, starts in the urothelial cells that line the
inside of the bladder. In 2012, approximately 430,000 people worldwide
were diagnosed with bladder cancer and 165,000 died from the disease.
The incidence of bladder cancer is elevated in North America, Europe,
North Africa, the Middle East, Australia and New Zealand.
KEYTRUDA is a humanized monoclonal antibody that works by increasing the
ability of the body’s immune system to help detect and fight tumor
cells. KEYTRUDA blocks the interaction between PD-1 and its ligands,
PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both
tumor cells and healthy cells.
KEYTRUDA is administered as an intravenous infusion over 30 minutes
every three weeks for the approved indications. KEYTRUDA for injection
is supplied in a 100 mg single use vial.
KEYTRUDA (pembrolizumab) Indications and Dosing
KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic melanoma at a dose of 2 mg/kg every three weeks.
KEYTRUDA is indicated for the treatment of patients with metastatic
non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as
determined by an FDA-approved test with disease progression on or after
platinum-containing chemotherapy, at a dose of 2 mg/kg every three
weeks. Patients with EGFR or ALK genomic tumor aberrations should have
disease progression on FDA-approved therapy for these aberrations prior
to receiving KEYTRUDA. This indication is approved under accelerated
approval based on tumor response rate and durability of response. An
improvement in survival or disease-related symptoms has not yet been
established. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
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 at a fixed dose
of 200 mg every three weeks. 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
Selected Important Safety Information for KEYTRUDA
Immune-mediated pneumonitis, including fatal cases, occurred in patients
receiving KEYTRUDA. Pneumonitis occurred in 32 (2.0%) of 1567 patients
with melanoma, including Grade 1 (0.8%), 2 (0.8%), and 3 (0.4%)
pneumonitis. Pneumonitis occurred in 19 (3.5%) of 550 patients with
NSCLC, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%)
pneumonitis and more frequently in patients with a history of
asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic
radiation (6.0%). Monitor patients for signs and symptoms of
pneumonitis. Evaluate suspected pneumonitis with radiographic imaging.
Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold
KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA (pembrolizumab)
for Grade 3 or 4 or recurrent Grade 2 pneumonitis.
Immune-mediated colitis occurred in 31 (2%) of 1567 patients with
melanoma, including Grade 2 (0.5%), 3 (1.1%), and 4 (0.1%) colitis.
Immune-mediated colitis occurred in 4 (0.7%) of 550 patients with NSCLC,
including Grade 2 (0.2%) or 3 (0.4%) 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.
Immune-mediated hepatitis occurred in patients receiving KEYTRUDA.
Hepatitis occurred in 16 (1%) of 1567 patients with melanoma, including
Grade 2 (0.1%), 3 (0.7%), and 4 (0.1%) hepatitis. Monitor patients for
changes in liver function. Administer corticosteroids for Grade 2 or
greater hepatitis and, based on severity of liver enzyme elevations,
withhold or discontinue KEYTRUDA.
Hypophysitis occurred in 13 (0.8%) of 1567 patients with melanoma,
including Grade 2 (0.3%), 3 (0.3%), and 4 (0.1%) hypophysitis.
Hypophysitis occurred in 1 (0.2 %) of 550 patients with NSCLC, which was
Grade 3 in severity. Monitor patients for signs and symptoms of
hypophysitis (including hypopituitarism and adrenal insufficiency).
Administer corticosteroids and hormone replacement as clinically
indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for
Grade 3 or 4 hypophysitis.
Hyperthyroidism occurred in 51 (3.3%) of 1567 patients with melanoma,
including Grade 2 (0.6%) and 3 (0.1%) hyperthyroidism. Hypothyroidism
occurred in 127 (8.1%) of 1567 patients with melanoma, including Grade 3
(0.1%) hypothyroidism. Hyperthyroidism occurred in 10 (1.8%) of 550
patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%)
hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients
with NSCLC, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. New or
worsening hypothyroidism occurred in 28 (14.6%) of 192 patients with
HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroid disorders can
occur at any time during treatment. Monitor patients for changes in
thyroid function (at the start of treatment, periodically during
treatment, and as indicated based on clinical evaluation) and for
clinical signs and symptoms of thyroid disorders. Administer replacement
hormones for hypothyroidism and manage hyperthyroidism with thionamides
and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for
Grade 3 or 4 hyperthyroidism.
Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3
(0.1%) of 2117 patients. Monitor patients for hyperglycemia or other
signs and symptoms of diabetes. Administer insulin for type 1 diabetes,
and withhold KEYTRUDA and administer anti-hyperglycemics in patients
with severe hyperglycemia.
Immune-mediated nephritis occurred in patients receiving KEYTRUDA
(pembrolizumab). Nephritis occurred in 7 (0.4%) of 1567 patients with
melanoma including, Grade 2 (0.2%), 3 (0.2%), and 4 (0.1%) nephritis.
Monitor patients for changes in renal function. Administer
corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for
Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.
Other clinically important immune-mediated adverse reactions can occur.
For suspected immune-mediated adverse reactions, ensure adequate
evaluation to confirm etiology or exclude other causes. Based on the
severity of the adverse reaction, withhold KEYTRUDA and administer
corticosteroids. Upon improvement to Grade 1 or less, initiate
corticosteroid taper and continue to taper over at least 1 month. Based
on limited data from clinical studies in patients whose immune-related
adverse reactions could not be controlled with corticosteroid use,
administration of other systemic immunosuppressants can be considered.
Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less
following corticosteroid taper. Permanently discontinue KEYTRUDA for any
Grade 3 immune-mediated adverse reaction that recurs and for any
life-threatening immune-mediated adverse reaction.
The following clinically significant, immune-mediated adverse reactions
occurred in less than 1% (unless otherwise indicated) of 1567 patients
with melanoma: arthritis (1.6%), exfoliative dermatitis, bullous
pemphigoid, uveitis, myositis, Guillain-Barré syndrome, myasthenia
gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures
arising in a patient with inflammatory foci in brain parenchyma. The
following clinically significant, immune-mediated adverse reactions
occurred in less than 1% of 550 patients with NSCLC: rash, vasculitis,
hemolytic anemia, serum sickness, and myasthenia gravis.
Severe and life-threatening infusion-related reactions have been
reported in 3 (0.1%) of 2117 patients. Monitor patients for signs and
symptoms of infusion-related reactions including rigors, chills,
wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever.
For Grade 3 or 4 reactions, stop infusion and permanently discontinue
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 (pembrolizumab) 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
In KEYNOTE-002, KEYTRUDA was discontinued due to adverse reactions in
12% of 357 patients with advanced melanoma; the most common (≥1%) were
general physical health deterioration (1%), asthenia (1%), dyspnea (1%),
pneumonitis (1%), and generalized edema (1%). Adverse reactions leading
to interruption of KEYTRUDA occurred in 14% of patients; the most common
(≥1%) were dyspnea (1%), diarrhea (1%), and maculopapular rash (1%). The
most common adverse reactions with KEYTRUDA vs chemotherapy were fatigue
(43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%),
constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs
20%), and decreased appetite (20% with KEYTRUDA). Corresponding
incidence rates are listed for chemotherapy only for those adverse
reactions that occurred at the same or lower rate than with KEYTRUDA.
KEYTRUDA was discontinued due to adverse reactions in 14% of 550
patients with NSCLC. Serious adverse reactions occurred in 38% of
patients. The most frequent serious adverse reactions reported in at
least 2% of patients were pleural effusion, pneumonia, dyspnea,
pulmonary embolism, and pneumonitis. The most common adverse reactions
(reported in at least 20% of patients) were fatigue (44%), cough (29%),
decreased appetite (25%), and dyspnea (23%).
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
(46%), decreased appetite (22%), and dyspnea (20%).
It is not known whether KEYTRUDA is excreted in human milk. Because many
drugs are excreted in human milk, instruct women to discontinue nursing
during treatment with KEYTRUDA and for 4 months after the final dose.
Safety and effectiveness of KEYTRUDA have not been established in
Our Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology
medicines to help people with cancer worldwide. At Merck Oncology,
helping people fight cancer is our passion and supporting accessibility
to our cancer medicines is our commitment. Our focus is on pursuing
research in immuno-oncology and we are accelerating every step in the
journey – from lab to clinic – to potentially bring new hope to people
As part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the fastest-growing development
programs in the industry. We are currently executing an expansive
research program that includes more than 350 clinical trials evaluating
our anti-PD-1 therapy across more than 30 tumor types. We also continue
to strengthen our immuno-oncology portfolio through strategic
acquisitions and are prioritizing the development of several promising
immunotherapeutic candidates with the potential to improve the treatment
of advanced cancers.
For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
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For more information, visit www.merck.com
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Please see Prescribing Information for KEYTRUDA (pembrolizumab) at
Patient Information/Medication Guide for KEYTRUDA at
Pamela Eisele, 267-305-3558
Kim Hamilton, 908-740-1863
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