Findings in Small Cell Lung Cancer and
Malignant Pleural Mesothelioma Show Overall Response Rates of 33.3
Percent and 20.0 Percent, Respectively, in KEYNOTE-028
Long-Term Data Demonstrate Durable Responses
in Difficult-to-Treat Cancers
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, today announced that updated findings from the phase 1b
KEYNOTE-028 study investigating the use of KEYTRUDA®
(pembrolizumab), the company’s anti-PD-1 therapy, in previously
treated patients with advanced small cell lung cancer (SCLC) and
malignant pleural mesothelioma, showed clinical activity and
durable responses in some patients. These data were featured in
oral presentations at the 17th World Conference on Lung Cancer
hosted by the International Association for the Study of Lung
Cancer.
“As data from our initial trials exploring KEYTRUDA mature, we
are encouraged to see durable clinical activity in
difficult-to-treat cancers such as small cell lung cancer and
malignant pleural mesothelioma, where new treatments are clearly
needed,” said Dr. Roger Dansey, senior vice president and
therapeutic area head, oncology late-stage development, Merck
Research Laboratories. “With our extensive immuno-oncology research
program, we are developing KEYTRUDA across a range of thoracic
malignancies, and we have additional studies underway in these two
cancer types.”
KEYNOTE-028 is an ongoing multi-cohort, non-randomized Phase 1b
basket trial evaluating the safety, tolerability, and anti-tumor
activity of KEYTRUDA monotherapy (10 mg/kg dosed every two weeks)
in more than 450 patients with PD-L1 positive tumors across 20
different types of cancer. PD-L1 positivity was defined as
expression in one percent or more of tumor and associated
inflammatory cells or positive staining in stroma. The primary
outcome measure is overall response rate (ORR), with secondary
outcome measures of progression-free survival (PFS), overall
survival (OS), and duration of response.
The KEYTRUDA (pembrolizumab) clinical development program
includes more than 30 tumor types in nearly 400 clinical trials,
including more than 200 trials that combine KEYTRUDA with other
cancer treatments. Merck has initiated a phase 2 trial,
KEYNOTE-158, to further evaluate KEYTRUDA in advanced solid tumors
including SCLC and malignant pleural mesothelioma.
Results from KEYNOTE-028 SCLC Cohort (Abstract
#OA05.01)
Data from the SCLC cohort of the KEYNOTE-028 trial were
presented in an oral presentation on Dec. 5 by Dr. Patrick Ott,
Dana-Farber Cancer Institute.
Updated findings from 24 heavily pre-treated patients with
advanced SCLC demonstrated a confirmed ORR of 33.3 percent (n=8/24)
(95% CI, 15.6%-55.3%), including one complete response and seven
partial responses. One patient had stable disease and 13 patients
had progressive disease. Responses were durable, with a median
duration of response of 19.4 months (95% CI, range: 3.6+ to
20.0+).
Additionally, the median PFS was 1.9 months (95% CI, 1.7-5.9),
with a six-month PFS rate of 28.6 percent and 12-month PFS rate of
23.8 percent. The median OS was 9.7 months (95% CI, 4.1-NR), with a
six-month OS rate of 66.0 percent and a 12-month OS rate of 37.7
percent.
The safety profile of KEYTRUDA was consistent with that observed
in previously reported studies. Grade 3-5 treatment-related
adverse events were asthenia, blood bilirubin increased, colitis
and intestinal ischemia (n=1 for all). Some patients experienced
adverse events of special interest, including autoimmune
thyroiditis, infusion site reaction, cytokine release syndrome and
colitis (n=1 for all).
“These long-term data, which show meaningful response rates and
durable responses in certain patients with small cell lung cancer,
are encouraging,” said Dr. Ott. “With these findings, we are
advancing understanding of the potential for immunotherapy to make
a difference for these patients.”
Results from KEYNOTE-028 Malignant Pleural Mesothelioma
Cohort (Abstract #OA13.03)
Data from the malignant pleural mesothelioma cohort of the
KEYNOTE-028 trial were presented in an oral presentation on Dec. 6
by Dr. Evan Alley, Abramson Cancer Center, University of
Pennsylvania.
Results showed a confirmed ORR of 20.0 percent (n=5/25) (95% CI,
6.8-40.7). All responses were partial responses and 13 patients had
stable disease. The median duration of response was 12.0 months
(range, 3.7-20.5+). In total, 60.9 percent of evaluable patients
experienced a decrease in tumor size.
Additionally, the median PFS was 5.4 months (95% CI, 3.4-7.5),
with a six-month PFS rate of 45.8 percent and a 12-month PFS rate
of 20.8 percent. Median OS was 18.0 months (95% CI, 9.4-NR), with a
six-month OS rate of 83.5 percent and a 12-month OS rate of 62.6
percent.
The safety profile of KEYTRUDA (pembrolizumab) was consistent
with that observed in previously reported studies. Grade 3
treatment-related adverse events were ALT increase, appetite
decrease, dyspnea, iridocyclitis, neutrophil count decreased,
pyrexia and thrombocytopenia (n=1 for all). Some patients
experienced adverse events of special interest, including
erythema/erythema multiforme, hypothyroidism, infusion-related
reaction, iridocyclitis and rhabdomyolysis (n=1 for all). There
were no Grade 4 or 5 treatment-related adverse events and no
treatment-related deaths.
About KEYTRUDA® (pembrolizumab)
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
Melanoma
KEYTRUDA is indicated for the treatment of patients with
unresectable or metastatic melanoma at a dose of 2 mg/kg every
three weeks until disease progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA 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 (pembrolizumab) 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.
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.
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.
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 (pembrolizumab) 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.
KEYTRUDA can cause other clinically important immune-mediated
adverse reactions. 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 (pembrolizumab) 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.
KEYTRUDA can cause severe or life-threatening infusion-related
reactions, 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.
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.
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
(pembrolizumab) 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 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%).
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.
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 pediatric patients.
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 nearly 400 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 125 years, Merck has been a global health care leader
working to help the world be well. Merck is known as MSD outside
the United States and Canada. 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. For more information, visit
www.merck.com and connect with us on Twitter, Facebook, 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 2015
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.
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