FDA Accepts Supplemental Biologics License Application, Assigns Priority Review and Grants Breakthrough Therapy Designation to Merck’s KEYTRUDA® (pembrolizumab) for First-Line Treatment of Patients with Advanced Non-Small Cell Lung Cancer
September 7, 2016 5:45 am ET
Merck Has Also Submitted a Marketing Authorization Application to the European Medicines Agency for KEYTRUDA in the Same Patient Population
Submissions Based on Data from KEYNOTE-024 Trial Showing Superior Progression-Free and Overall Survival Compared to Chemotherapy in Patients Whose Tumors Express High Levels of PD-L1
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
accepted for Priority Review the supplemental Biologics License
Application (sBLA) for KEYTRUDA® (pembrolizumab), the
company’s anti-PD-1 therapy, for the first-line treatment of patients
with advanced non-small cell lung cancer (NSCLC) whose tumors express
PD-L1, with a PDUFA, or target action, date of Dec. 24, 2016.
Additionally, the FDA granted Breakthrough Therapy Designation for this
indication. Merck has also submitted a Marketing Authorization
Application to the European Medicines Agency for this indication.
The submissions were based on data from the pivotal phase 3 KEYNOTE-024
study, which showed that KEYTRUDA monotherapy resulted in superior
progression-free survival (PFS) as well as overall survival (OS)
compared with standard chemotherapy in patients with advanced NSCLC
whose tumors expressed high levels of PD-L1 (tumor proportion score of
50 percent or more). Based on the results, the trial was stopped early
to give patients still on chemotherapy the opportunity to receive
KEYTRUDA. Merck filed for approval of KEYTRUDA in the first-line setting
at a dose of 200 mg every three weeks, the dose studied in KEYNOTE-024.
“Chemotherapy has been the foundation of first-line treatment for
non-small cell lung cancer for decades, so the significant improvement
in survival in patients with high PD-L1 expression seen with KEYTRUDA
compared to chemotherapy is welcome news,” said Dr. Roger M. Perlmutter,
president, Merck Research Laboratories. “We appreciate the opportunity
to work with regulatory authorities to make KEYTRUDA a first-line
treatment option in non-small cell lung cancer.”
The FDA’s Breakthrough Therapy Designation is intended to expedite the
availability of promising new therapies that are planned for use, alone
or in combination, to treat a serious or life-threatening disease or
condition when preliminary clinical evidence indicates substantial
improvement over existing therapies on one or more clinically
significant endpoints. Merck previously announced that KEYTRUDA
(pembrolizumab) was granted breakthrough status for specific patients
with advanced melanoma, metastatic NSCLC in previously treated patients,
microsatellite instability high metastatic colorectal cancer, and
relapsed or refractory classical Hodgkin Lymphoma.
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 Indications and Dosing
KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic melanoma at a dose of 2 mg/kg every three weeks.
KEYTRUDA is indicated 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, at a dose of 2 mg/kg every three
weeks. Patients with EGFR or ALK genomic tumor aberrations should have
disease progression on FDA-approved therapy for these aberrations prior
to receiving KEYTRUDA (pembrolizumab). 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. An sBLA is currently under review with the FDA for
full approval of the existing second-line NSCLC indication. The
application is based on data from KEYNOTE-010, a pivotal phase 2/3
confirmatory trial which demonstrated improved survival with KEYTRUDA
compared to standard chemotherapy in previously treated patients with
advanced NSCLC who had PD-L1 expression on one percent or more of the
cancer cells. The FDA target action date is Oct. 24, 2016.
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 at a fixed dose
of 200 mg every three weeks. 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
Selected Important Safety Information for KEYTRUDA
Immune-mediated pneumonitis occurred in 19 (3.5%) of 550 patients,
including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis
and occurred more frequently in patients with a history of
asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic
radiation (6.0%). 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.
Immune-mediated colitis occurred in 4 (0.7%) of 550 patients, including
Grade 2 (0.2%) or 3 (0.4%) 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.
Immune-mediated hepatitis occurred in patients 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 1 (0.2%) of 550 patients, 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 clinically indicated.
Withhold KEYTRUDA (pembrolizumab) for Grade 2; withhold or discontinue
for Grade 3 or 4 hypophysitis.
Hyperthyroidism occurred in 10 (1.8%) of 550 patients, including Grade 2
(0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%)
of 550 patients, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism.
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 4 hyperthyroidism.
Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3
(0.1%) of 2117 patients. 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.
Immune-mediated nephritis occurred in patients receiving KEYTRUDA.
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 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% of 550 patients: rash, vasculitis, hemolytic
anemia, serum sickness, and myasthenia gravis.
Severe and life-threatening infusion-related reactions have been
reported in 3 (0.1%) of 2117 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.
KEYTRUDA was discontinued due to adverse reactions in 14% of 550
patients. Serious adverse reactions occurred in 38% of patients. The
most frequent serious adverse reactions reported in at least 2% 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%), cough (29%), decreased appetite
(25%), and dyspnea (23%).
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
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
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 330 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.
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,
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Please see Prescribing Information for KEYTRUDA (pembrolizumab) at
Patient Information/Medication Guide for KEYTRUDA at
Pamela Eisele, 267-305-3558
Courtney Ronaldo, 908-236-1108
Teri Loxam, 908-740-1986
Amy Klug, 908-740-1898