Data to Be Presented at 2017 ASCO Annual
Meeting Include Findings in Patients with Locally Advanced
Triple-Negative (TNBC) and Hormone Receptor-Positive/HER2-Negative
(HR+/HER2-) Breast Cancers
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, and QuantumLeap Healthcare Collaborative, today announced
results from the Phase 2 I-SPY 2 TRIAL investigating KEYTRUDA®
(pembrolizumab), Merck’s anti-PD-1 therapy, in combination with
standard therapy [paclitaxel followed by doxorubicin and
cyclophosphamide (AC)] as a neoadjuvant (pre-operative) treatment
for patients with locally advanced triple-negative breast cancer
(TNBC) or hormone receptor-positive/HER2-negative (HR+/HER2-)
breast cancer. Findings showed that the addition of KEYTRUDA
increased the estimated pathologic complete response (pCR) rate
nearly threefold in patients with TNBC (60% vs 20%) and in patients
with HR+/HER2- breast cancer (34% vs 13%) compared to standard
therapy. Overall, based on Bayesian predictive probability of
success in a confirmatory Phase 3 trial, KEYTRUDA has graduated
from the I-SPY 2 TRIAL for all signatures in which it was tested
(TNBC, all HER2-, and HR+/HER2-). Data will be presented today by
Dr. Rita Nanda, The University of Chicago, during an oral session
at the 2017 American Society of Clinical Oncology (ASCO) Annual
Meeting in Chicago (Abstract #506) and will also be presented in
subsequent “Best of ASCO” events scheduled throughout the year.
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“KEYTRUDA in combination with standard therapy tripled the rate
of pathologic complete responses in HER2- patients in the I-SPY 2
Trial,” said Laura J. Esserman, M.D., MBA, professor of surgery and
radiology and director of the Carol Franc Buck Breast Care Center
at UCSF Helen Diller Family Comprehensive Cancer Center, and the
overall principal investigator for the I-SPY TRIALS. “The regimen
indicates a new and important treatment pathway and gives us
well-grounded hope for new options for patients with these
aggressive breast cancers – and that’s potentially very good
news.”
“We recognize that there is a critical unmet need for patients
with certain breast cancer subtypes and believe that combination
regimens will be important to advancing patient care,” said Dr.
Eric Rubin, vice president of early-stage development, clinical
oncology, Merck Research Laboratories. “The results presented at
ASCO, which add to the growing body of evidence for KEYTRUDA in
various types of breast cancer, are exciting and demonstrate the
potential benefit of KEYTRUDA in these patients.”
The I-SPY 2 TRIAL (NCT01042379), sponsored by QuantumLeap
Healthcare Collaborative, is a standing Phase 2 randomized,
controlled, multi-center trial for women with newly diagnosed,
locally advanced breast cancer (Stage II/III), and is designed to
screen promising new treatments and identify which therapies are
most effective in specific patient subgroups based on molecular
characteristics (biomarker signatures). The trial is an adaptive
study design assessing the combination of biologically targeted
investigational drugs with standard chemotherapy in the neoadjuvant
setting, compared to standard chemotherapy alone. The primary
endpoint is to determine whether the combination of certain
therapies increases the probability of pCR in the breast and the
lymph nodes at the time of surgery. The data presented at ASCO from
the I-SPY 2 TRIAL were based on results observed in patients at
high risk of relapse using up-front tumor profiling (including HR
status, HER2 status, and the MammaPrint 70-gene signature test).
Patients were treated with weekly standard chemotherapy
(paclitaxel) for 12 weeks, with or without KEYTRUDA
(pembrolizumab), followed by doxorubicin and cyclophosphamide (AC)
every 3 weeks for four cycles. Sixty-nine patients were adaptively
randomized to receive KEYTRUDA in the trial from December 2015
until it graduated in November 2016. In total, 46 patients have
undergone surgery; the other 23 have on-therapy MRI
assessments.
In patients with TNBC, an absolute increase in the estimated pCR
rate of 40 percent was observed in the KEYTRUDA arm (based on the
estimated pCR rate of 60% with KEYTRUDA plus standard therapy
compared to 20% with standard therapy alone). In patients with
HER2- breast cancer, an absolute increase in the estimated pCR rate
of 30 percent was observed in the KEYTRUDA arm (based on the
estimated pCR rate of 46% with KEYTRUDA plus standard therapy
compared to 16% with standard therapy alone). In patients with
HR+/HER2- breast cancer, an absolute increase in the estimated pCR
rate of 21 percent was observed in the KEYTRUDA (pembrolizumab) arm
(based on the estimated pCR rate of 34% with KEYTRUDA plus standard
therapy compared to 13% with standard therapy alone). The Bayesian
model estimated pCR rates appropriately adjust to characteristics
of the I-SPY 2 population, including MammaPrint status.
Signature
Estimated pCR Rate
(95% Probability Interval)
ProbabilityKEYTRUDA
IsSuperior toControl
PredictiveProbability
ofSuccess inPhase 3
KEYTRUDA Plus Standard
Therapy
StandardTherapy Alone
TNBC
0.60
(0.43 – 0.78)
0.20
(0.06 – 0.33)
>99% >99%
All
HER2- 0.46
(0.34 – 0.58)
0.16
(0.06 – 0.27)
>99% 99%
HR+/HER2- 0.34
(0.19 – 0.48)
0.13
(0.03 – 0.24)
>99%
88%
The safety profile of KEYTRUDA was consistent with that observed
in previously reported studies across tumors. In the KEYTRUDA arm,
Grade 3-5 treatment-related adverse events include diarrhea (n=5),
febrile neutropenia (n=5), fatigue (n=4), anemia (n=3), nausea
(n=3), neutropenia without fever (n=1), peripheral motor neuropathy
(n=1), peripheral sensory neuropathy (n=1) and vomiting (n=1).
Immune-mediated adverse events of Grade 3-5 include adrenal
insufficiency (n=5), hepatitis (n=2), colitis (n=1) and
hypothyroidism (n=1). Five of six patients presented with adrenal
insufficiency after completion of AC (21-24 weeks after starting
KEYTRUDA), and one presented during KEYTRUDA treatment (5 weeks
after starting KEYTRUDA).
“Not all breast cancers are the same – and there has continued
to be a significant gap in the treatment options available for
patients with certain subtypes, particularly TNBC,” said Dr. Rita
Nanda, medical oncologist at The University of Chicago. “The
results observed in this trial are not only encouraging, but
demonstrate the potential for treatment combinations that can make
a difference in patient outcomes.”
About I-SPY and the I-SPY 2 TRIAL
The I-SPY (Investigation of Serial Studies to Predict Your
Therapeutic Response with Imaging And moLecular Analysis) TRIAL is
conducted by a consortium that brings together the U.S. Food and
Drug Administration (FDA), leading academic medical centers, and
patient advocates, as well as Merck and other pharmaceutical and
biotech companies.
The I-SPY 2 TRIAL is a collaborative effort among academic
investigators from 20 major cancer research centers across the U.S.
and QuantumLeap Healthcare Collaborative, the FDA, and the
Foundation for the National Institutes of Health (FNIH) Cancer
Biomarkers Consortium. Major supporters include The Safeway
Foundation and the Bill Bowes Foundation.
The I-SPY 2 TRIAL’s adaptive statistical design was developed by
the pioneering principal investigators for the I-SPY trial, Laura
J. Esserman, M.D., MBA, and Donald A. Berry, Ph.D., professor of
biostatistics at The University of Texas MD Anderson Cancer Center
and founder of Berry Consultants in collaboration with the FDA,
industry, and many leading academic collaborators including the
Agents working group chair (Doug Yee, M.D. from the University of
Minnesota) and the Trial Operations working group chair (Angie
DeMichele, M.D. from the University of Pennsylvania). The trial is
a unique collaborative effort where over 50 clinicians are actively
engaged in the conduct of the trial.
The I-SPY 2 TRIAL adaptive-trial design is based on Bayesian
predictive probability that a biological regimen will be shown to
be statistically superior to standard therapy in an equally
randomized 300-patient confirmatory trial. Regimens that have a
high Bayesian predictive probability of showing superiority in at
least one of 10 predefined signatures graduate from the trial.
Regimens are dropped for futility if they show a low predictive
probability of showing superiority over standard therapy in all 10
signatures. A maximum total of 120 patients can be assigned to each
experimental regimen. A regimen can graduate early and at any time
after having 60 patients assigned to it.
About KEYTRUDA® (pembrolizumab)
Injection
KEYTRUDA is an anti-PD-1 therapy that works by increasing the
ability of the body’s immune system to help detect and fight tumor
cells. KEYTRUDA is a humanized monoclonal antibody that blocks the
interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby
activating T lymphocytes which may affect both tumor cells and
healthy cells.
Studies of KEYTRUDA – from the largest immuno-oncology program
in the industry with more than 500 trials – include a wide variety
of cancers and treatment settings. The KEYTRUDA clinical program
seeks to understand factors that predict a patient’s likelihood of
benefitting from treatment with KEYTRUDA, including the exploration
of several different biomarkers across a broad range of tumors.
KEYTRUDA (pembrolizumab) is administered as an intravenous
infusion over 30 minutes every three weeks for the approved
indications. KEYTRUDA for injection is supplied in a 100 mg
single-dose vial.
KEYTRUDA (pembrolizumab) Indications and
Dosing
Melanoma
KEYTRUDA is indicated for the treatment of patients with
unresectable or metastatic melanoma at a fixed dose of 200 mg every
three weeks until disease progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA, as a single agent, is indicated for the first-line
treatment of patients with metastatic non-small cell lung cancer
(NSCLC) whose tumors have high PD-L1 expression [tumor proportion
score (TPS) ≥50%] as determined by an FDA-approved test, with no
EGFR or ALK genomic tumor aberrations.
KEYTRUDA, as a single agent, is also indicated for the treatment
of patients with metastatic NSCLC whose tumors express PD-L1 (TPS
≥1%) as determined by an FDA-approved test, with disease
progression on or after platinum-containing chemotherapy. Patients
with EGFR or ALK genomic tumor aberrations should have disease
progression on FDA-approved therapy for these aberrations prior to
receiving KEYTRUDA.
KEYTRUDA, in combination with pemetrexed and carboplatin, is
indicated for the first-line treatment of patients with metastatic
nonsquamous NSCLC. This indication is approved under accelerated
approval based on tumor response rate and progression-free
survival. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials.
In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of
200 mg every three weeks until disease progression, unacceptable
toxicity, or up to 24 months in patients without disease
progression.
When administering KEYTRUDA in combination with chemotherapy,
KEYTRUDA should be administered prior to chemotherapy when given on
the same day. See also the Prescribing Information for pemetrexed
and carboplatin.
Head and Neck Cancer
KEYTRUDA (pembrolizumab) is indicated for the treatment of
patients with recurrent or metastatic head and neck squamous cell
carcinoma (HNSCC) with disease progression on or after
platinum-containing chemotherapy. This indication is approved under
accelerated approval based on tumor response rate and durability of
response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed
dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without
disease progression.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric
patients with refractory classical Hodgkin lymphoma (cHL), or who
have relapsed after three or more prior lines of therapy. This
indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for
this indication may be contingent upon verification and description
of clinical benefit in the confirmatory trials. In adults with cHL,
KEYTRUDA is administered at a fixed dose of 200 mg every three
weeks until disease progression or unacceptable toxicity, or up to
24 months in patients without disease progression. In pediatric
patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg
(up to a maximum of 200 mg) every three weeks until disease
progression or unacceptable toxicity, or up to 24 months in
patients without disease progression.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma who are not eligible
for cisplatin-containing chemotherapy. This indication is approved
under accelerated approval based on tumor response rate and
duration of response. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
the confirmatory trials.
KEYTRUDA is also indicated for the treatment of patients with
locally advanced or metastatic urothelial carcinoma who have
disease progression during or following platinum-containing
chemotherapy or within 12 months of neoadjuvant or adjuvant
treatment with platinum-containing chemotherapy.
In locally advanced or metastatic urothelial carcinoma, KEYTRUDA
is administered at a fixed dose of 200 mg every three weeks until
disease progression or unacceptable toxicity, or up to 24 months in
patients without disease progression.
Microsatellite Instability-High (MSI-H) Cancer
KEYTRUDA (pembrolizumab) is indicated for the treatment of adult
and pediatric patients with unresectable or metastatic
microsatellite instability-high (MSI-H) or mismatch repair
deficient (dMMR)
- solid tumors that have progressed
following prior treatment and who have no satisfactory alternative
treatment options, or
- colorectal cancer that has progressed
following treatment with fluoropyrimidine, oxaliplatin, and
irinotecan.
This indication is approved under accelerated approval based on
tumor response rate and durability of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in the confirmatory trials. The
safety and effectiveness of KEYTRUDA in pediatric patients with
MSI-H central nervous system cancers have not been established.
In adult patients with MSI-H cancer, KEYTRUDA is administered at
a fixed dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without
disease progression. In pediatric patients with MSI-H cancer,
KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of
200 mg) every three weeks until disease progression or unacceptable
toxicity, or up to 24 months in patients without disease
progression.
Selected Important Safety Information for
KEYTRUDA® (pembrolizumab)
KEYTRUDA can cause immune-mediated pneumonitis, including fatal
cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving
KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%),
and 5 (0.1%) pneumonitis, and occurred more frequently in patients
with a history of prior thoracic radiation (6.9%) compared to those
without (2.9%). Monitor patients for signs and symptoms of
pneumonitis. Evaluate suspected pneumonitis with radiographic
imaging. Administer corticosteroids for Grade 2 or greater
pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue
KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.
KEYTRUDA can cause immune-mediated colitis. Colitis occurred in
48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for
signs and symptoms of colitis. Administer corticosteroids for Grade
2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3;
permanently discontinue KEYTRUDA for Grade 4 colitis.
KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred
in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for
changes in liver function. Administer corticosteroids for Grade 2
or greater hepatitis and, based on severity of liver enzyme
elevations, withhold or discontinue KEYTRUDA.
KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17
(0.6%) of 2799 patients receiving KEYTRUDA (pembrolizumab),
including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis.
Monitor patients for signs and symptoms of hypophysitis (including
hypopituitarism and adrenal insufficiency). Administer
corticosteroids and hormone replacement as clinically indicated.
Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3
or 4 hypophysitis.
KEYTRUDA can cause thyroid disorders, including hyperthyroidism,
hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96
(3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237
(8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2
(6.2%) and 3 (0.1%) hypothyroidism. Thyroiditis occurred in 16
(0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.3%) thyroiditis. Monitor patients for changes in thyroid
function (at the start of treatment, periodically during treatment,
and as indicated based on clinical evaluation) and for clinical
signs and symptoms of thyroid disorders. Administer replacement
hormones for hypothyroidism and manage hyperthyroidism with
thionamides and beta-blockers as appropriate. Withhold or
discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.
KEYTRUDA can cause type 1 diabetes mellitus, including diabetic
ketoacidosis, which have been reported in 6 (0.2%) of 2799
patients. Monitor patients for hyperglycemia or other signs and
symptoms of diabetes. Administer insulin for type 1 diabetes, and
withhold KEYTRUDA and administer antihyperglycemics in patients
with severe hyperglycemia.
KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred
in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for
changes in renal function. Administer corticosteroids for Grade 2
or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently
discontinue KEYTRUDA for Grade 3 or 4 nephritis.
KEYTRUDA can cause other clinically important immune-mediated
adverse reactions. These immune-mediated reactions may occur in any
organ system. For suspected immune-mediated adverse reactions,
ensure adequate evaluation to confirm etiology or exclude other
causes. Based on the severity of the adverse reaction, withhold
KEYTRUDA and administer corticosteroids. Upon improvement to Grade
1 or less, initiate corticosteroid taper and continue to taper over
at least 1 month. Based on limited data from clinical studies in
patients whose immune-related adverse reactions could not be
controlled with corticosteroid use, administration of other
systemic immunosuppressants can be considered. Resume KEYTRUDA when
the adverse reaction remains at Grade 1 or less following
corticosteroid taper. Permanently discontinue KEYTRUDA for any
Grade 3 immune-mediated adverse reaction that recurs and for any
life-threatening immune-mediated adverse reaction.
The following clinically significant immune-mediated adverse
reactions occurred in less than 1% (unless otherwise indicated) of
2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous
pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré
syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic
anemia, and partial seizures arising in a patient with inflammatory
foci in brain parenchyma. In addition, myelitis and myocarditis
were reported in other clinical trials, including classical Hodgkin
lymphoma, and postmarketing use.
Solid organ transplant rejection has been reported in
postmarketing use of KEYTRUDA (pembrolizumab). Treatment with
KEYTRUDA may increase the risk of rejection in solid organ
transplant recipients. Consider the benefit of treatment with
KEYTRUDA vs the risk of possible organ rejection in these
patients.
KEYTRUDA can cause severe or life-threatening infusion-related
reactions, including hypersensitivity and anaphylaxis, which have
been reported in 6 (0.2%) of 2799 patients. Monitor patients for
signs and symptoms of infusion-related reactions, including rigors,
chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia,
and fever. For Grade 3 or 4 reactions, stop infusion and
permanently discontinue KEYTRUDA.
Immune-mediated complications, including fatal events, occurred
in patients who underwent allogeneic hematopoietic stem cell
transplantation (HSCT) after being treated with KEYTRUDA. Of 23
patients with cHL who proceeded to allogeneic HSCT after treatment
with KEYTRUDA on any trial, 6 patients (26%) developed
graft-versus-host-disease (GVHD), one of which was fatal, and 2
patients (9%) developed severe hepatic veno-occlusive disease (VOD)
after reduced-intensity conditioning, one of which was fatal. Cases
of fatal hyperacute GVHD after allogeneic HSCT have also been
reported in patients with lymphoma who received a PD-1
receptor–blocking antibody before transplantation. These
complications may occur despite intervening therapy between PD-1
blockade and allogeneic HSCT. Follow patients closely for early
evidence of transplant-related complications such as hyperacute
GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile
syndrome, hepatic VOD, and other immune-mediated adverse reactions,
and intervene promptly.
Based on its mechanism of action, KEYTRUDA can cause fetal harm
when administered to a pregnant woman. If used during pregnancy, or
if the patient becomes pregnant during treatment, apprise the
patient of the potential hazard to a fetus. Advise females of
reproductive potential to use highly effective contraception during
treatment and for 4 months after the last dose of KEYTRUDA.
In KEYNOTE-006, KEYTRUDA was discontinued due to adverse
reactions in 9% of 555 patients with advanced melanoma; adverse
reactions leading to discontinuation in more than one patient were
colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction
(0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse
reactions leading to interruption of KEYTRUDA occurred in 21% of
patients; the most common (≥1%) was diarrhea (2.5%). The most
common adverse reactions with KEYTRUDA (pembrolizumab) vs
ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA),
rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding
incidence rates are listed for ipilimumab only for those adverse
reactions that occurred at the same or lower rate than with
KEYTRUDA.
In KEYNOTE-002, KEYTRUDA was discontinued due to adverse
reactions in 12% of 357 patients with advanced melanoma; the most
common (≥1%) were general physical health deterioration (1%),
asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized
edema (1%). Adverse reactions leading to interruption of KEYTRUDA
occurred in 14% of patients; the most common (≥1%) were dyspnea
(1%), diarrhea (1%), and maculopapular rash (1%). The most common
adverse reactions with KEYTRUDA vs chemotherapy were fatigue (43%
with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%),
constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea
(20% vs 20%), and decreased appetite (20% with KEYTRUDA).
Corresponding incidence rates are listed for chemotherapy only for
those adverse reactions that occurred at the same or lower rate
than with KEYTRUDA.
KEYTRUDA monotherapy was discontinued due to adverse reactions
in 8% of 682 patients with metastatic NSCLC. The most common
adverse event resulting in permanent discontinuation of KEYTRUDA
was pneumonitis (1.8%). Adverse reactions leading to interruption
of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were
diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme
elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%).
The most common adverse reactions (occurring in at least 20% of
patients and at a higher incidence than with docetaxel) were
decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea
(20% vs 18%).
When KEYTRUDA was administered in combination with carboplatin
and pemetrexed (carbo/pem), KEYTRUDA was discontinued in 10% of 59
patients. The most common adverse reaction resulting in
discontinuation of KEYTRUDA (≥2%) was acute kidney injury (3.4%).
Adverse reactions leading to interruption of KEYTRUDA occurred in
39% of patients; the most common (≥2%) were fatigue (8%),
neutrophil count decreased (8%), anemia (5%), dyspnea (3.4%), and
pneumonitis (3.4%).The most common adverse reactions (≥20%) with
KEYTRUDA compared to carbo/pem alone were fatigue (71% vs 50%),
nausea (68% vs 56%), constipation (51% vs 37%), rash (42% vs 21%),
vomiting (39% vs 27%), dyspnea (39% vs 21%), diarrhea (37% vs 23%),
decreased appetite (31% vs 23%), headache (31% vs 16%), cough (24%
vs 18%), dizziness (24% vs 16%), insomnia (24% vs 15%), pruritus
(24% vs 4.8%), peripheral edema (22% vs 18%), dysgeusia (20% vs
11%), alopecia (20% vs 3.2%), upper respiratory tract infection
(20% vs 3.2%), and arthralgia (15% vs 24%). This study was not
designed to demonstrate a statistically significant difference in
adverse reaction rates for KEYTRUDA (pembrolizumab) as compared to
carbo/pem alone for any specified adverse reaction.
KEYTRUDA was discontinued due to adverse reactions in 17% of 192
patients with HNSCC. Serious adverse reactions occurred in 45% of
patients. The most frequent serious adverse reactions reported in
at least 2% of patients were pneumonia, dyspnea, confusional state,
vomiting, pleural effusion, and respiratory failure. The most
common adverse reactions (reported in at least 20% of patients)
were fatigue, decreased appetite, and dyspnea. Adverse reactions
occurring in patients with HNSCC were generally similar to those
occurring in patients with melanoma or NSCLC, with the exception of
increased incidences of facial edema (10% all Grades; 2.1% Grades 3
or 4) and new or worsening hypothyroidism.
KEYTRUDA was discontinued due to adverse reactions in 5% of 210
patients with cHL, and treatment was interrupted due to adverse
reactions in 26% of patients. Fifteen percent (15%) of patients had
an adverse reaction requiring systemic corticosteroid therapy.
Serious adverse reactions occurred in 16% of patients. The most
frequent serious adverse reactions (≥1%) included pneumonia,
pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two
patients died from causes other than disease progression; one from
GVHD after subsequent allogeneic HSCT and one from septic shock.
The most common adverse reactions (occurring in ≥20% of patients)
were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal
pain (21%), diarrhea (20%), and rash (20%).
In KEYNOTE-052, KEYTRUDA was discontinued due to adverse
reactions in 11% of 370 patients with locally advanced or
metastatic urothelial carcinoma. The most common adverse reactions
(in ≥20% of patients) were fatigue (38%), musculoskeletal pain
(24%), decreased appetite (22%), constipation (21%), rash (21%),
and diarrhea (20%). Eighteen patients (5%) died from causes other
than disease progression. Five patients (1.4%) who were treated
with KEYTRUDA experienced sepsis which led to death, and 3 patients
(0.8%) experienced pneumonia which led to death. Adverse reactions
leading to interruption of KEYTRUDA occurred in 22% of patients;
the most common (≥1%) were liver enzyme increase, diarrhea, urinary
tract infection, acute kidney injury, fatigue, joint pain, and
pneumonia. Serious adverse reactions occurred in 42% of patients,
the most frequent (≥2%) of which were urinary tract infection,
hematuria, acute kidney injury, pneumonia, and urosepsis.
In KEYNOTE-045, KEYTRUDA was discontinued due to adverse
reactions in 8% of 266 patients with locally advanced or metastatic
urothelial carcinoma. The most common adverse reaction resulting in
permanent discontinuation of KEYTRUDA was pneumonitis (1.9%).
Adverse reactions leading to interruption of KEYTRUDA occurred in
20% of patients; the most common (≥1%) were urinary tract infection
(1.5%), diarrhea (1.5%), and colitis (1.1%). The most common
adverse reactions (≥20%) in patients who received KEYTRUDA vs those
who received chemotherapy were fatigue (38% vs 56%),
musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%), decreased
appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs 13%).
Serious adverse reactions occurred in 39% of KEYTRUDA
(pembrolizumab)-treated patients, the most frequent (≥2%) of which
were urinary tract infection, pneumonia, anemia, and
pneumonitis.
The most common adverse reactions (reported in ≥20% of patients)
were fatigue, pruritus, diarrhea, decreased appetite, rash,
pyrexia, cough, dyspnea, musculoskeletal pain, constipation, and
nausea.
It is not known whether KEYTRUDA is excreted in human milk.
Because many drugs are excreted in human milk, instruct women to
discontinue nursing during treatment with KEYTRUDA and for 4 months
after the final dose.
About QuantumLeap Healthcare Collaborative
QuantumLeap Healthcare Collaborative, a non-profit foundation,
was established in 2005 as a collaboration between medical
researchers at University of California at San Francisco, and
Silicon Valley entrepreneurs. QuantumLeap’s mission is to
accelerate transfer of high-impact research in clinical processes
and systems technology into widespread adoption so that patients
and physicians can benefit from the research as soon as
practicable. QuantumLeap provides operational, financial and
regulatory oversight to I-SPY. For more information, visit:
http://www.quantumleaphealth.org.
Merck’s Focus on Cancer
Our goal is to translate breakthrough science into innovative
oncology medicines to help people with cancer worldwide. At Merck,
helping people fight cancer is our passion and supporting
accessibility to our cancer medicines is our commitment. Our focus
is on pursuing research in immuno-oncology and we are accelerating
every step in the journey – from lab to clinic – to potentially
bring new hope to people with cancer.
As part of our focus on cancer, Merck is committed to exploring
the potential of immuno-oncology with one of the fastest-growing
development programs in the industry. We are currently executing an
expansive research program that includes more than 500 clinical
trials evaluating our anti-PD-1 therapy across more than 30 tumor
types. We also continue to strengthen our immuno-oncology portfolio
through strategic acquisitions and are prioritizing the development
of several promising immunotherapeutic candidates with the
potential to improve the treatment of advanced cancers.
For more information about our oncology clinical trials, visit
www.merck.com/clinicaltrials.
About Merck
For more than a century, Merck, a leading global
biopharmaceutical company known as MSD outside of the United States
and Canada, has been inventing for life, bringing forward medicines
and vaccines for many of the world’s most challenging diseases.
Through our prescription medicines, vaccines, biologic therapies
and animal health products, we work with customers and operate in
more than 140 countries to deliver innovative health solutions. We
also demonstrate our commitment to increasing access to health care
through far-reaching policies, programs and partnerships. Today,
Merck continues to be at the forefront of research to advance the
prevention and treatment of diseases that threaten people and
communities around the world - including cancer, cardio-metabolic
diseases, emerging animal diseases, Alzheimer’s disease and
infectious diseases including HIV and Ebola. For more information,
visit www.merck.com 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.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20170605005510/en/
Media:MerckPamela Eisele, 267-305-3558orMerckAnn Bush,
908-740-6677orKing + Company for QuantumLeapCaren Browning,
212-561-7464orInvestors:Teri Loxam, 908-740-1986orAmy Klug,
908-740-1898
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