Responses Observed in Three-Quarters of Heavily Pre-Treated Multiple Myeloma Patients Receiving KEYTRUDA® (pembrolizumab) Combined With Lenalidomide and Dexamethasone
December 7, 2015 7:00 am ET
Findings Presented at the 57th American Society of Hematology Annual Meeting Demonstrate Activity of KEYTRUDA Therapy in Previously-Treated Multiple Myeloma Patients When Combined with Lenalidomide and Dexamethasone
KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
announced today new study findings investigating the use of KEYTRUDA®
(pembrolizumab), the company’s anti-PD-1 therapy, in combination with
lenalidomide and low-dose dexamethasone (two commonly used treatments
for multiple myeloma) in patients whose disease has progressed after at
least two lines of prior therapy, including a proteasome inhibitor and
an IMiD (immune modulatory drug). The initial findings from the ongoing
Phase 1 KEYNOTE-023 study showed an overall response rate (ORR) of 76
percent (n=13/17), as assessed by the International Myeloma Working
Group (IMWG) 2006 Criteria. These results will be presented today at the
57th American Society of Hematology (ASH) Annual Meeting by
Jesus San Miguel, M.D., Ph.D., Clínica Universidad de Navarra, Pamplona,
Spain (Abstract #505). Based in part on these data, Merck has initiated
two Phase 3 studies evaluating KEYTRUDA in the treatment of multiple
myeloma.
“Many patients with multiple myeloma relapse after their initial
treatment, reinforcing the need for additional treatment options,” said
Dr. Jesus San Miguel. “These findings highlight the potential of
combining KEYTRUDA with an IMiD and dexamethasone in patients who have
multiple myeloma.”
“Our clinical program explores the potential for KEYTRUDA across broad
patient populations, including in combination with other medicines,”
said Roger Dansey, M.D., senior vice president and therapeutic area
head, oncology late-stage development, Merck Research Laboratories. “We
are encouraged by these results, showing responses in patients who have
relapsed following treatment for multiple myeloma when treated with
KEYTRUDA in combination with lenalidomide and dexamethasone, and look
forward to building on these data.”
Results from KEYNOTE-023 Presented at ASH
In the study with 50 heavily pre-treated patients, initial findings from
17 patients who were treated with KEYTRUDA (pembrolizumab) in
combination with lenalidomide and low-dose dexamethasone demonstrated an
ORR of 76 percent (n=13/17) (per IMWG 2006), including four very good
partial responses (24%) and nine partial responses (53%).
Adverse events in all 50 patients were consistent with previously
reported safety data for KEYTRUDA as well as lenalidomide and low-dose
dexamethasone. Grade 3 or 4 treatment-related adverse events included:
neutropenia (n=11), thrombocytopenia (n=4), diarrhea (n=1), fatigue
(n=1), anemia (n=4), hyperglycemia (n=3) and muscle spasms (n=1).
Immune-mediated adverse events included: adrenal insufficiency (n=1),
hyperthyroidism (n=2), hypothyroidism (n=2), and thyroiditis (n=1). No
treatment-related deaths were reported.
About the KEYTRUDA Development Program and KEYNOTE-023
Merck is conducting a broad hematological malignancy program with
approximately 20 clinical trials, including four registration-enabling
studies and more than 15 combinations across a variety of lymphomas,
myeloma, leukemia, and other hematologic malignancies.
Registration-enabling trials of KEYTRUDA are currently enrolling
patients in melanoma, NSCLC, head and neck cancer, bladder cancer,
gastric cancer, colorectal cancer, esophageal cancer, breast cancer,
Hodgkin lymphoma, multiple myeloma and other tumors, with further trials
in planning for other cancers.
KEYNOTE-023 is a global, open-label, Phase 1 study designed to evaluate
KEYTRUDA treatment in combination with dexamethasone and two different
doses of lenalidomide in approximately 75 patients with
relapsed/refractory multiple myeloma (RRMM). Patients will receive
KEYTRUDA (2 mg/kg every two weeks) in combination with lenalidomide (10
mg or 25 mg) or KEYTRUDA (200 mg fixed dose every two weeks) with
lenalidomide (10 mg or 25 mg); all patients will receive 40 mg low-dose
dexamethasone weekly. Primary endpoints include safety and tolerability;
secondary endpoints include ORR, duration of response, progression-free
survival (PFS), and overall survival (OS).
About Multiple Myeloma
Multiple myeloma is a cancer of blood plasma cells in which abnormal
plasma cells multiply uncontrollably in the bone marrow and occasionally
in other parts of the body. Manifestations of the disease often include
bone pain and fractures, and may include kidney problems, a weakened
immune system weakness, and confusion. Multiple myeloma is the second
most common blood cancer. In 2015, an estimated 26,850 people are
expected to be diagnosed and an estimated 11,240 people are expected to
die of the disease in the U.S. alone.
About KEYTRUDA® (pembrolizumab) Injection
100 mg
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 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 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. Patients with EGFR or ALK genomic
tumor aberrations should have disease progression on FDA-approved
therapy for these aberrations prior to receiving KEYTRUDA. KEYTRUDA is
also indicated at the same dosing for the treatment of patients with
unresectable or metastatic melanoma and disease progression following
ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. These
indications are 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 these indications may be contingent upon verification and
description of clinical benefit in the confirmatory trials.
Selected Important Safety Information for KEYTRUDA®
(pembrolizumab)
Pneumonitis, including fatal cases, occurred in patients receiving
KEYTRUDA. Pneumonitis occurred in 12 (2.9%) of 411 melanoma patients,
including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients,
respectively, receiving KEYTRUDA. 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 in patients, receiving KEYTRUDA. 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.
Colitis (including microscopic colitis) occurred in 4 (1%) of 411
patients with melanoma, including Grade 2 or 3 cases in 1 (0.2%) and 2
(0.5%) patients, respectively, receiving KEYTRUDA. Colitis occurred in 4
(0.7 %) of 550 patients with NSCLC, including Grade 2 (0.2%) or 3 (0.4%)
colitis in patients 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 occurred in patients receiving KEYTRUDA. Hepatitis (including
autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients with
melanoma, 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 with melanoma,
including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each)
patient, receiving KEYTRUDA. 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 indicated. Withhold KEYTRUDA for Grade 2 and withhold or
discontinue for Grade 3 or Grade 4 hypophysitis.
Hyperthyroidism occurred in 5 (1.2%) of 411 patients with melanoma,
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 with melanoma, including a Grade 3 case in 1 (0.2%)
patient, receiving KEYTRUDA. Hyperthyroidism occurred in 10 (1.8%) of
550 patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%).
Hypothyroidism occurred in 38 (6.9%) of 550 patients with NSCLC,
including Grade 2 (5.5%) or 3 (0.2%). 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 Grade 4 hyperthyroidism.
Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred
in patients receiving KEYTRUDA. 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.
Nephritis occurred in patients receiving KEYTRUDA. Nephritis occurred in
3 (0.7%) patients with melanoma, 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.
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 of the adverse reaction to Grade 1 or
less, initiate corticosteroid taper and continue to taper over at least
1 month. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or
less following steroid taper. Permanently discontinue KEYTRUDA for any
severe or Grade 3 immune-mediated adverse reaction that recurs and for
any life-threatening immune-mediated adverse reaction.
Across clinical studies with KEYTRUDA, the following clinically
significant, immune-mediated adverse reactions have occurred: bullous
pemphigoid and Guillain-Barré syndrome. The following clinically
significant, immune-mediated adverse reactions occurred in less than 1%
of patients with melanoma treated with KEYTRUDA: exfoliative dermatitis,
uveitis, arthritis, myositis, 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
treated with KEYTRUDA: rash, vasculitis, hemolytic anemia, serum
sickness, and myasthenia gravis.
Infusion-related reactions, including severe and life-threatening
reactions, have occurred in patients receiving KEYTRUDA. Monitor
patients for signs and symptoms of infusion related reactions including
rigors, chills, wheezing, pruritus, flushing, rash, hypotension,
hypoxemia, and fever. For severe or life-threatening 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.
Among the 411 patients with metastatic melanoma, KEYTRUDA was
discontinued for adverse reactions in 9% of 411 patients. Adverse
reactions, reported in at least two patients that led to discontinuation
of KEYTRUDA were: pneumonitis, renal failure, and pain. Serious adverse
reactions occurred in 36% of patients. The most frequent serious adverse
reactions, reported in 2% or more of patients, were renal failure,
dyspnea, pneumonia, and cellulitis. The most common adverse reactions
(reported in at least 20% of patients) were fatigue (47%), cough (30%),
nausea (30%), pruritus (30%), rash (29%), decreased appetite (26%),
constipation (21%), arthralgia (20%), and diarrhea (20%).
Among the 550 patients with metastatic NSCLC, KEYTRUDA was discontinued
due to adverse reactions in 14% of patients. Serious adverse reactions
occurred in 38% of patients. The most frequent serious adverse reactions
reported in 2% or more 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%),
decreased appetite (25%), dyspnea (23%), and cough (29%).
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 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 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
with cancer. For more information about our oncology clinical trials,
visit www.merck.com/clinicaltrials.
About Merck
Today’s Merck is 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
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demonstrate our commitment to increasing access to health care through
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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 the Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf
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