New Data Investigating Merck’s KEYTRUDA® (pembrolizumab) in Advanced Non-Small Cell Lung Cancer and Mesothelioma to Be Presented in Clinical Trials Plenary Session at AACR 2015
March 18, 2015 4:19 pm ET
Data to be Presented Across Multiple Tumor Types for KEYTRUDA and MK-8628 (OTX015), an Investigational BET-Bromodomain Inhibitor
KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced that new data evaluating KEYTRUDA®
(pembrolizumab), the company’s anti-PD-1 therapy, in both advanced
non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma
will be presented as part of the Clinical Trials Plenary Session on
Sunday, April 19 at the American Association for Cancer Research (AACR)
Annual Meeting in Philadelphia, April 18 – 22.
The NSCLC data will be the first presentation of new efficacy and safety
findings for KEYTRUDA from 495 patients, including validation of PD-L1
expression (abstract #CT104). These data are from the largest,
multi-center Phase 1b (KEYNOTE-001) study of an anti-PD-1 therapy. With
the mesothelioma findings (abstract #CT103), data evaluating KEYTRUDA
will have been presented in eight different types of cancer.
“Our clinical program is investigating the potential of KEYTRUDA in a
broad range of cancers where innovative approaches are truly needed –
these data to be presented at AACR illustrate this effort,” said Dr.
Roger Dansey, senior vice president, Late-Stage Oncology Clinical
Development, Merck Research Laboratories. “At AACR, we look forward to
sharing new data for KEYTRUDA across a range of challenging cancer
types, especially in non-small cell lung cancer and mesothelioma.”
Presentations of Merck Oncology Compounds
In total, data from 14 abstracts evaluating KEYTRUDA or MK-8628
(OTX015), Merck’s investigational BET-bromodomain inhibitor, will be
presented at AACR 2015. Pre-clinical and early phase data to be
presented span multiple tumor types – such as prostate cancer, blood
cancer and NSCLC. A full listing of abstracts included in the 2015 AACR
program is below:
(Abstract #CT104) Late-Breaker Presentation: Efficacy
of pembrolizumab (MK-3475) and relationship with PD-L1 expression in
patients with non-small cell lung cancer (NSCLC): Findings from
KEYNOTE-001. E. Garon. Sunday, April 19, 1:05 PM EDT. Location:
Terrace Ballroom I (400 Level).
(Abstract #CT103) Late-Breaker Presentation: Clinical
safety and efficacy of pembrolizumab (MK-3475) in patients with
malignant pleural mesothelioma (MPM): Preliminary results from
KEYNOTE-028. E. Alley. Sunday, April 19, 12:45 PM EDT. Location:
Terrace Ballroom I (400 Level).
(Abstract #256) Poster Presentation: Identification
of additional cancers likely to respond to anti-PD-1 therapy
(pembrolizumab): Evaluation of PD-L1 expression in a large molecular
tumor profiling gene expression database. M. Ayers. Sunday, April
19, 1:00 PM-5:00 PM EDT. Location: Section 12.
(Abstract #269) Poster Presentation: Evaluation of
the antitumor activity of anti-PD-1 immunotherapy as a single agent
and in combination with approved agents in preclinical tumor models. E.
Pinheiro. Sunday, April 19, 1:00 PM-5:00 PM EDT. Location: Section 12.
(Abstract #570) Poster Presentation: PD-L1 expression
in paired non-small cell lung cancer tumor samples. J. Kim.
Sunday, April 19, 1:00 PM-5:00 PM EDT. Location: Section 24.
(Abstract #1307) Poster Presentation: Assessment of
gene expression in peripheral blood from patients with advanced
melanoma using RNA-seq before and after treatment with anti-PD-1
therapy with pembrolizumab (MK-3475). M. Ayers. Monday, April 20,
8:00 AM-12:00 PM EDT. Location: Section 12.
(Abstract #1328) Poster Presentation: Molecular
characterization of mouse syngeneic tumor models in response to
treatment with anti-PD-1 immunotherapy. H. Hirsch. Monday, April
20, 8:00 AM-12:00 PM EDT. Location: Section 12.
(Abstract #4303) Poster Presentation: Programmed
death ligand 1 (PD-L1) expression in paired melanoma tumor samples. T.
Steiniche. Tuesday, April 21, 1:00 PM-5:00 PM EDT. Location: Section
(Abstract #2625) Poster Presentation: Targeting
prostate cancer stem cells (CSCs) with the novel BET bromodomain (BRD)
protein inhibitor OTX015. G. Civenni. Monday, April 20, 1:00
PM-5:00 PM EDT. Location: Section 30.
(Abstract #3526) Poster Presentation: OTX015 effects
in triple-negative breast cancer (TNBC) models are independent of
hypoxia conditions and synergistic with other anticancer agents. R.
Vazquez. Tuesday, April 21, 8:00 AM-12:00 PM EDT. Location: Section 28.
(Abstract #3527) Poster Presentation: OTX015, a novel
BET-bromodomain (BET-BRD) inhibitor, displays antitumoral effects in
orthotopic and heterotopic models of human glioblastoma. L.
Astorgues-xerri. Tuesday, April 21, 8:00 AM-12:00 PM EDT. Location:
(Abstract #3530) Poster Presentation: Gene expression
profile of OTX015, a BET bromodomain inhibitor, in preclinical models
of non-small-cell lung cancer (NSCLC) and small-cell lung cancer
(SCLC) models. M. Riveiro. Tuesday, April 21, 8:00 AM-12:00 PM
EDT. Location: Section 28.
(Abstract #4511) Poster Presentation: Pharmacokinetics
of OTX015 in a phase Ib dose-finding study of patients with
hematologic malignancies: Preliminary results of a population PK
analysis. E. Odore. Tuesday, April 21, 1:00 PM-5:00 PM EDT.
Location: Section 32.
(Abstract #4731) Minisymposium: Targeting
super-enhancer induced gene expression with the novel BRD4 inhibitor
OTX015 in preclinical models of MYCN-amplified neuroblastoma. A.
Henssen. Tuesday, April 21, 3:50 PM – 4:05 PM EDT. Location: Room 120.
For more information including a complete list of abstract titles,
please visit the AACR website at http://www.aacr.org.
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
Merck is advancing a broad and fast-growing clinical development program
for KEYTRUDA with more than 70 clinical trials – across more than 30
tumor types and over 8,000 patients – both as a monotherapy and in
combination with other therapies.
About MK-8628 (OTX015)
MK-8628 (OTX015) is an investigational, novel oral BET (bromodomain)
inhibitor, which is currently in Phase 1b studies for the treatment of
hematological malignancies and advanced solid tumors. BET proteins are
considered potential therapeutic targets in cancer, as they play a
pivotal role in regulating the transcription of key regulators of cancer
cell growth and survival, including c-Myc. Interim data from
ongoing Phase 1 clinical studies of MK-8628 have demonstrated meaningful
clinical activity in patients with hematological malignancies. An
international, open-label Phase 1 study evaluating MK-8628 in five
different solid tumors was initiated in November 2014.
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
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
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
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.
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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.
Pamela Eisele, 267-305-3558
Claire Mulhearn, 908-236-1118
Joseph Romanelli, 908-740-1986
Justin Holko, 908-740-1879