FDA Approves Merck’s KEYTRUDA® (pembrolizumab) for Adult and Pediatric Patients with Unresectable or Metastatic, Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient Cancer
May 23, 2017 3:34 pm ET
KEYTRUDA Now Approved for Patients with MSI-H or Mismatch Repair Deficient Solid Tumors That Have Progressed Following Prior Treatment and Who Have No Satisfactory Alternative Treatment Options, Which Includes MSI-H or Mismatch Repair Deficient Colorectal Cancer That Has Progressed Following Treatment with a Fluoropyrimidine, Oxaliplatin, and Irinotecan
KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced that the U.S. Food and Drug Administration (FDA)
has approved a new indication for KEYTRUDA® (pembrolizumab),
the company’s anti-PD-1 therapy. KEYTRUDA is now indicated for the
treatment of adult and pediatric patients with unresectable or
metastatic, microsatellite instability-high (MSI-H) or mismatch repair
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 a
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.
The recommended dose of KEYTRUDA in adults is 200 mg administered as an
intravenous infusion over 30 minutes every three weeks until disease
progression, unacceptable toxicity, or up to 24 months in patients
without disease progression. In children, the recommended dose of
KEYTRUDA is 2 mg/kg (up to a maximum of 200 mg) administered as an
intravenous infusion over 30 minutes every three weeks until disease
progression or unacceptable toxicity, or up to 24 months in patients
without disease progression.
Immune-mediated adverse reactions occurred with KEYTRUDA including
pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Based
on the severity of the adverse reaction, KEYTRUDA (pembrolizumab) should
be withheld or discontinued and corticosteroids administered if
appropriate. KEYTRUDA can also cause severe or life-threatening
infusion-related reactions. Monitor patients for signs and symptoms of
infusion-related reactions; 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.
Female patients of reproductive potential should be advised of the
potential hazard to a fetus. For more information regarding
immune-mediated adverse reactions, please read the additional Selected
Safety Information below.
“The FDA’s approval of this new indication for KEYTRUDA further supports
Merck’s commitment to helping people with difficult-to-treat cancers,”
said Dr. Roger M. Perlmutter, president, Merck Research Laboratories.
“We are thankful to the researchers, as well as the patients and their
families who helped make today’s approval possible.”
Further details will be included in a news release to follow.
Selected Important Safety Information for KEYTRUDA
Injection 100 mg
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
KEYTRUDA (pembrolizumab) 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. 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 involve 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
(pembrolizumab) 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. Treatment with KEYTRUDA may increase the risk of rejection
in solid organ transplant recipients. Consider 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
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.
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.
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,
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“company”) includes “forward-looking statements” within the meaning of
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respect to pipeline products that the products will receive the
necessary regulatory approvals or that they will prove to be
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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
Patient Information/Medication Guide for KEYTRUDA at
Pamela Eisele, 267-305-3558
Teri Loxam, 908-740-1986