Merck’s KEYTRUDA® (pembrolizumab) Demonstrates Superior Progression-Free and Overall Survival Compared to Chemotherapy as First-Line Treatment in Patients with Advanced Non-Small Cell Lung Cancer
June 16, 2016 5:45 am ET
KEYNOTE-024 Studied Patients Whose Tumors Expressed 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 KEYNOTE-024 trial investigating the use of
KEYTRUDA® (pembrolizumab), in patients with previously
untreated advanced non-small cell lung cancer (NSCLC) whose tumors
expressed high levels of PD-L1 (tumor proportion score of 50 percent or
more), met its primary endpoint. In this trial, KEYTRUDA was superior
compared to chemotherapy for both the primary endpoint of
progression-free survival (PFS), and the secondary endpoint of overall
survival (OS). Based on these results, an independent Data Monitoring
Committee (DMC) has recommended that the trial be stopped, and that
patients receiving chemotherapy in KEYNOTE-024 be offered the
opportunity to receive KEYTRUDA.
“We believe that the KEYNOTE-024 results have the potential to change
the therapeutic paradigm in first-line treatment of non-small-cell lung
cancer,” said Dr. Roger M. Perlmutter, president, Merck Research
Laboratories. “We look forward to sharing these data with the medical
community and with regulatory authorities around the world.”
The safety profile of KEYTRUDA in this trial was consistent with that
observed in previously reported studies in patients with advanced NSCLC.
Results from KEYNOTE-024 will be presented at an upcoming medical
Merck currently has the largest immuno-oncology clinical development
program across the industry and is advancing five registration-enabling
studies for NSCLC with KEYTRUDA as a monotherapy and in combination.
KEYNOTE-024 is a randomized, pivotal, phase 3 study (ClinicalTrials.gov,
NCT02142738) evaluating KEYTRUDA (pembrolizumab) monotherapy compared to
standard of care (SOC) platinum-based chemotherapies in the treatment of
patients with advanced NSCLC. Patients enrolled were those who had
received no prior systemic chemotherapy treatment for their advanced
disease and whose tumors expressed high levels of PD-L1 (defined as a
tumor proportion score of 50 percent or more) as determined by a central
laboratory using an immunohistochemistry assay. The study randomized 305
patients to receive KEYTRUDA (200 mg every three weeks) or SOC
platinum-based chemotherapies: paclitaxel+carboplatin,
pemetrexed+carboplatin, pemetrexed+cisplatin, gemcitabine+carboplatin,
or gemcitabine+cisplatin. Pemetrexed maintenance therapy was permitted
for patients with non-squamous histologies. In addition, patients
randomized to the control had the option of crossing over to
pembrolizumab upon disease progression. The primary endpoint is PFS;
secondary endpoints are OS and overall response rate (ORR).
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 for the treatment of patients with unresectable or
KEYTRUDA is also 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. Patients with EGFR or ALK genomic
tumor aberrations should have disease progression on FDA-approved
therapy for these aberrations prior to receiving KEYTRUDA. 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.
KEYTRUDA is administered at a dose of 2 mg/kg as an intravenous infusion
over 30 minutes every three weeks for the approved indications.
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 for Grade 2; withhold or discontinue for Grade 3 or 4
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 (pembrolizumab) for Grade 3 or 4
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
(pembrolizumab) 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%).
No formal pharmacokinetic drug interaction studies have been conducted
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 (pembrolizumab) 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
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 270 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
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Please see Prescribing Information for KEYTRUDA (pembrolizumab) at
Patient Information/Medication Guide for KEYTRUDA at
Pamela Eisele, 267-305-3558
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