Early Findings with KEYTRUDA® (pembrolizumab), Merck’s Anti-PD-1 Therapy, in Patients with Advanced Pleural Mesothelioma Presented at AACR Annual Meeting
April 19, 2015 11:45 am ET
KEYTRUDA Demonstrated 28 Percent Overall Response Rate and 76 Percent Disease Control Rate in Difficult-to-Treat Cancer
First Findings from KEYNOTE-028, Merck’s Innovative Basket Trial in 20 Cancers
KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the first presentation of data investigating the use of
KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy,
in 25 patients with advanced pleural mesothelioma, a difficult-to-treat
cancer of the lining of the lungs, abdomen and other organs. The early
findings presented showed an overall response rate (confirmed and
unconfirmed) of 28 percent with KEYTRUDA in patients with tumors that
expressed PD-L1. Additionally, 48 percent of patients had stable
disease, resulting in a disease control rate of 76 percent. These data,
from KEYNOTE-028, will be presented today at the American Association
for Cancer Research (AACR) Annual Meeting by Dr. Evan Alley, Abramson
Cancer Center, University of Pennsylvania, and were part of the AACR
official press program (abstract #CT103). This is the first data to be
presented from KEYNOTE-028, Merck’s innovative basket trial designed to
evaluate the efficacy and safety of KEYTRUDA in patients with 20
difficult-to-treat cancers.
“This presentation at AACR marks the first time that data involving an
anti-PD-1 therapy have been presented in pleural mesothelioma, which is
a rare, hard-to-treat cancer with very limited treatment options,” said
Dr. Alley, clinical associate professor of medicine, Abramson Cancer
Center. “While early, the disease control rates observed in this study
are very encouraging, and indicate that further study is warranted to
evaluate the potential role of KEYTRUDA in the treatment of malignant
pleural mesothelioma.”
“This unique study is helping to accelerate our understanding of where
KEYTRUDA may work in cancers with limited or no treatment options,” said
Dr. Roger Dansey, therapeutic area head and senior vice president,
oncology late stage development, Merck Research Laboratories. “These
early data in advanced pleural mesothelioma reinforce the clinically
meaningful results we are seeing with KEYTRUDA across multiple cancers.”
At the time of the analysis, 40 percent of patients (n=10/25) remained
on treatment. Adverse events in the study were consistent with
previously reported safety data for KEYTRUDA. The most common
treatment-related adverse events (occurring in greater than twenty
percent of patients) were fatigue (24%) and nausea (24%). Two Grade 3
treatment-related adverse events occurred: ALT increased (n=1) and
thrombocytopenia (n=1). Some patients experienced adverse events of
special interest, including rash (n=4), ALT/AST increased (n=1),
hypersensitivity (n=1) and iridocyclitis (n=1); two required a dose
interruption (one because of ALT/AST increased, one because of
iridocyclitis). No patients discontinued as a result of
treatment-related adverse events, and there were no treatment-related
deaths.
About the KEYNOTE-028 Study
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 320 patients
with PD-L1 positive advanced solid tumors that have not responded to
current therapy or for which current therapy is not appropriate.
About KEYTRUDA® (pembrolizumab)
KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody that blocks
the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By
binding to the PD-1 receptor and blocking the interaction with the
receptor ligands, KEYTRUDA releases the PD-1 pathway-mediated inhibition
of the immune response, including the anti-tumor immune response.
KEYTRUDA is indicated in the United States at a dose of 2 mg/kg
administered as an intravenous infusion over 30 minutes every three
weeks for the treatment of patients with unresectable or metastatic
melanoma and disease progression following ipilimumab and, if BRAF V600
mutation positive, a BRAF inhibitor. 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
confirmatory trials.
Merck is advancing a broad and fast-growing clinical development program
for KEYTRUDA with more than 85 clinical trials – across more than 30
tumor types and over 14,000 patients – both as a monotherapy and in
combination with other therapies.
Selected Important Safety Information for KEYTRUDA®
Pneumonitis occurred in 12 (2.9%) of 411 patients with advanced melanoma
receiving KEYTRUDA (the approved indication in the United States),
including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients,
respectively. 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
pneumonitis.
Colitis (including microscopic colitis) occurred in 4 (1%) of 411
patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients
respectively, receiving KEYTRUDA. 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.
Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411
patients, including a Grade 4 case in 1 (0.2%) patient, receiving
KEYTRUDA. 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 2 (0.5%) of 411 patients, including a Grade 2
case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving
KEYTRUDA. Monitor for signs and symptoms of hypophysitis. Administer
corticosteroids for Grade 2 or greater hypophysitis. Withhold KEYTRUDA
for Grade 2; withhold or discontinue for Grade 3; and permanently
discontinue KEYTRUDA for Grade 4 hypophysitis.
Nephritis occurred in 3 (0.7%) patients receiving KEYTRUDA, consisting
of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of
interstitial nephritis with renal failure (0.5%), one Grade 3 and one
Grade 4. 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.
Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including Grade 2
or 3 cases in 2 (0.5%) and 1 (0.2%) patients respectively, receiving
KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411 patients,
including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA.
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 corticosteroids for Grade 3 or greater hyperthyroidism.
Withhold KEYTRUDA for Grade 3; permanently discontinue KEYTRUDA for
Grade 4 hyperthyroidism. Isolated hypothyroidism may be managed with
replacement therapy without treatment interruption and without
corticosteroids.
Other clinically important immune-mediated adverse reactions can occur.
The following clinically significant, immune-mediated adverse reactions
occurred in less than 1% of patients treated with KEYTRUDA: exfoliative
dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic
anemia, partial seizures arising in a patient with inflammatory foci in
brain parenchyma, adrenal insufficiency, myasthenic syndrome, optic
neuritis, and rhabdomyolysis.
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 of the adverse reaction to Grade 1 or
less, initiate corticosteroid taper and continue to taper over at least
1 month. Restart KEYTRUDA if the adverse reaction remains at Grade 1 or
less. Permanently discontinue KEYTRUDA for any severe or Grade 3
immune-mediated adverse reaction that recurs and for any
life-threatening immune-mediated adverse reaction.
Based on its mechanism of action, KEYTRUDA may 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.
For the treatment of advanced melanoma, KEYTRUDA was discontinued for
adverse reactions in 6% of 89 patients who received the recommended dose
of 2 mg/kg and 9% of 411 patients across all doses studied. Serious
adverse reactions occurred in 36% of patients receiving KEYTRUDA. The
most frequent serious adverse drug reactions reported in 2% or more of
patients were renal failure, dyspnea, pneumonia, and cellulitis.
The most common adverse reactions (reported in ≥20% of patients) were
fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%),
decreased appetite (26%), constipation (21%), arthralgia (20%), and
diarrhea (20%).
The recommended dose of KEYTRUDA is 2 mg/kg administered as an
intravenous infusion over 30 minutes every three weeks until disease
progression or unacceptable toxicity. No formal pharmacokinetic drug
interaction studies have been conducted with KEYTRUDA. 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. Safety and effectiveness of KEYTRUDA have not
been established in pediatric patients.
About Malignant Mesothelioma
Malignant mesotheliomas are cancers of a covering tissue that lines the
lung, abdomen, heart and testes. There are four main types of that are
named based on where they develop: the chest (pleural mesotheliomas);
the abdomen (peritoneal mesotheliomas); the covering around the heart
(pericardial mesotheliomas); and the covering layer of the testicles
(mesotheliomas of the tunica vaginalis). About 3,000 new cases of
mesothelioma are diagnosed each year in the United States; about 75
percent of all cases are pleural mesotheliomas. The main risk factor for
developing mesothelioma is exposure to asbestos; others include
infection with simian virus 40 (SV40), older age (65 or older), and male
gender.
Our Focus on Cancer
Our goal is to translate breakthrough science into biomedical
innovations to help people with cancer worldwide. For Merck Oncology,
helping people fight cancer is our passion, supporting accessibility to
our cancer medicines is our commitment, and pursuing research in
immuno-oncology is our focus to potentially bring new hope to people
with cancer. For more information about our oncology clinical trials,
visit www.merck.com/clinicaltrials.
About Merck
Today’s Merck is a global healthcare leader working to help the world be
well. Merck is known as MSD outside the United States and Canada.
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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 the Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.
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