Longer-Term Findings to Be Presented at 2017
ASCO Annual Meeting
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, today announced updated overall survival (OS) findings from
KEYNOTE-024, the phase 3 study evaluating KEYTRUDA®
(pembrolizumab), the company’s anti-PD-1 therapy, as a monotherapy
compared to platinum-containing chemotherapy in the first-line
treatment of patients with advanced non-small cell lung cancer
(NSCLC) whose tumors express high levels of PD-L1 (tumor proportion
score [TPS] of 50 percent or more). The study included patients
with squamous and non-squamous NSCLC with no EGFR or ALK genomic
tumor aberrations and demonstrated a reduction in the risk of death
by 37 percent for KEYTRUDA compared to chemotherapy based on 19
months of median follow-up (HR, 0.63 [95% CI, 0.46-0.88]; p =
0.003). Additionally, in an exploratory analysis, progression-free
survival 2 (PFS2) – a clinical endpoint used to assess the impact
of next-line treatment on disease control – was substantially
improved for patients in the KEYTRUDA group compared to the
chemotherapy group. These data are being presented in an oral
session at the 2017 American Society of Clinical Oncology (ASCO)
Annual Meeting in Chicago on Tuesday, June 6, from 9:45 – 9:57 a.m.
CDT (Location: Hall D1) (Abstract #9000).
With approximately eight additional months of follow-up, data
showed continued OS benefit with KEYTRUDA over chemotherapy in the
first-line treatment of patients with advanced NSCLC whose tumors
expressed high levels of PD-L1 – showing an 18-month OS rate of
61.2 percent in the KEYTRUDA group compared to 43.0 percent in the
chemotherapy group; the 12-month OS rate was 70.3 percent in the
KEYTRUDA group compared to 54.8 percent in the chemotherapy
group.
For PFS2, findings based on 19 months of median follow-up showed
a 46 percent reduction in the risk of progression after the start
of the second-line regimen or death in patients initially
randomized to KEYTRUDA compared to patients initially randomized to
chemotherapy (HR, 0.54 [95% CI, 0.40-0.72]; p < 0.001]).
“From the start of the KEYTRUDA program in non-small cell lung
cancer, one of our goals has been to demonstrate the value of
KEYTRUDA monotherapy in appropriate patient populations,” said Dr.
Roger Dansey, senior vice president and therapeutic area head,
oncology late-stage development, Merck Research
Laboratories. “With updated data from KEYNOTE-024, as well as
from other studies in our clinical development program, we are
establishing the role of KEYTRUDA in the treatment of advanced
non-small cell lung cancer.”
Merck has a robust clinical development program for KEYTRUDA in
lung cancer, with multiple registration-enabling studies currently
underway. The KEYTRUDA clinical development program includes more
than 30 tumor types in more than 500 clinical trials, including
more than 300 trials that combine KEYTRUDA with other cancer
treatments.
“These results from additional follow-up in KEYNOTE-024 –
including improved overall survival despite significant crossover –
give us further confidence in KEYTRUDA as a first-line treatment
for patients with non-small cell lung cancer whose tumors express
high levels of PD-L1,” said Prof. Martin Reck, head of the
department of thoracic oncology, LungenClinic Grosshansdorf,
Germany.
Key Findings from the KEYNOTE-024 Study
KEYNOTE-024 is a randomized, phase 3 study of 305 patients with
metastatic NSCLC who were assigned either KEYTRUDA (pembrolizumab)
as monotherapy (n=154) or standard of care platinum-based
chemotherapy (n=151). Enrollment criteria included: having no prior
systemic chemotherapy treatment for their advanced disease, tumors
without an EGFR sensitizing mutation or ALK translocation, and
tumors expressing high levels of PD-L1 (TPS of 50 percent or more)
as determined by a central laboratory using the Dako PD-L1 IHC 22C3
PharmDx test, from Agilent Technologies. The primary endpoint was
progression-free survival (PFS) and the key secondary endpoint was
OS. Other secondary endpoints include overall response rate (ORR)
and safety. Exploratory endpoints include PFS2 and duration of
response.
Data presented at ASCO are based on a median follow-up of 19.1
months (range: 14.3-27.6) and include findings from 79 patients who
crossed over from the chemotherapy arm to receive KEYTRUDA, per
study protocol, and 12 patients who received anti-PD-1 therapy
outside of study crossover. Results show that KEYTRUDA maintained
an OS benefit over chemotherapy in patients whose tumors expressed
high levels of PD-L1 (TPS of 50 percent or more), with a 37 percent
reduction in the risk of death (HR, 0.63 [95% CI, 0.46-0.88]; p =
0.003). The 12-month OS rate was 70.3 percent in the KEYTRUDA group
compared to 54.8 percent in the chemotherapy group; at 18 months,
the OS rate was 61.2 percent in the KEYTRUDA group compared to 43.0
percent in the chemotherapy group. The median OS had not yet been
reached in the KEYTRUDA group (95% CI, 19.4-NE), compared to 14.5
months in the chemotherapy group (95% CI, 9.8-19.6).
In an exploratory analysis of PFS2 – a clinical endpoint used to
assess the impact of next-line treatment on disease control –
findings showed a 46 percent reduction in the risk of progression
after initiation of the second-line regimen or death in patients
initially randomized to KEYTRUDA compared to patients initially
randomized to chemotherapy (HR, 0.54 [95% CI, 0.40-0.72]; p <
0.001]). The 12-month PFS2 rate was 59.7 percent in the KEYTRUDA
group and 38.5 percent in the chemotherapy group; the 18-month PFS2
rate was 51.0 percent in the KEYTRUDA group and 24.6 percent in the
chemotherapy group. The median PFS2 was 18.3 months in the KEYTRUDA
group (95% CI, 12.7-NE) compared to 8.4 months in the chemotherapy
group (95% CI, 6.8-9.8).
A safety analysis was not performed for this data set.
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
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 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 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 (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.
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 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, 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 (pembrolizumab) 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.
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%).
It is not known whether KEYTRUDA (pembrolizumab) 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 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
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Kenilworth, N.J., USA
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USA (the “company”) includes “forward-looking statements” within
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the products will receive the necessary regulatory approvals or
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# # #
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.
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