Data Investigating KEYTRUDA® (pembrolizumab), Merck’s Anti-PD-1 Therapy, in Patients with Classical Hodgkin Lymphoma Presented at ASH Annual Meeting
December 6, 2014 1:00 pm ET
Overall Response Rate of 66 Percent Observed in KEYTRUDA-treated Patients Whose Cancer Progressed on Brentuximab Vedotin
Phase 2 Study Planned for the First Half of 2015 (KEYNOTE-087)
SAN FRANCISCO–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
announced today early study findings demonstrating that KEYTRUDA® (pembrolizumab),
the company’s anti-PD-1 therapy, achieved an overall response rate of 66
percent, as assessed by International Harmonization Project response
criteria (n=19/29: 95% CI, 46-82), in transplant-ineligible and failure
patients with relapsed/refractory classical Hodgkin Lymphoma (cHL) whose
disease progressed on or after treatment with brentuximab vedotin.
Complete remission was achieved in 21 percent of patients (n=6/29) in
the study. At the time of analysis, 89 percent of responses were ongoing
(n=17/19) with the median duration of response not yet reached (range 1+
to 185+ days). These early findings, from the ongoing Phase 1b
KEYNOTE-013 study, were described for the first time as part of the
official press program at the 56th American Society of Hematology (ASH)
Annual Meeting in San Francisco (ABSTRACT #290) and will be presented in
an oral session on December 8th by Dr. Craig Moskowitz,
Memorial Sloan Kettering Cancer Center.
“These early data presented at ASH 2014 are very promising and show
response rates of 66 percent with pembrolizumab in patients with
classical Hodgkin Lymphoma,” said Dr. Craig Moskowitz, clinical
director, division of hematologic oncology, Memorial Sloan Kettering
Cancer Center. “There are few options for patients with multiple
relapsed or refractory, classical Hodgkin Lymphoma, and pembrolizumab
should continue to be studied for the treatment of this cancer.”
“Merck’s immuno-oncology development program spans more than 30
different types of cancer including a focus on blood cancers like
classical Hodgkin Lymphoma,” said Dr. Alise Reicin, vice president,
global clinical development, oncology, Merck Research Laboratories.
“Response rates being observed with KEYTRUDA in these patients support
the potential role of the PD-1 pathway in blood cancers. We look forward
to initiating additional studies including a Phase 2 trial in classical
Hodgkin Lymphoma in the first half of 2015.”
Early Findings for Investigational Use of KEYTRUDA in
Relapsed/Refractory cHL
Data from a cohort of the ongoing Phase 1b KEYNOTE-013 study evaluated
KEYTRUDA monotherapy at 10 mg/kg every two weeks in patients with
relapsed/refractory classical Hodgkin Lymphoma who had progressed on or
after treatment with brentuximab vedotin after failure of autologous
stem-cell transplant, or who were transplant-ineligible (n=29).
|
Antitumor Activity by International Harmonization Project |
|||||||
|
Transplant |
Transplant |
Total |
|||||
| Overall Response Rate | 4 (44) | 15 (75) | 19 (66) | ||||
| Complete Remission | 2 (22) | 4 (20) | 6 (21) | ||||
| Partial Remission | 2 (22) | 11 (55) | 13 (45) | ||||
| Stable Disease | 3 (33) | 3 (15) | 6 (21) | ||||
| Clinical Benefit Rate | 7 (78) | 18 (90) | 25 (86) | ||||
| Progressive Disease | 2 (22) | 2 (10) | 4 (14) | ||||
|
*Analysis cut-off date: November 17, 2014 |
|||||||
Median time to response was 12 weeks. In the transplant
ineligible/refusal patient group, eight patients were ineligible and one
patient refused transplant, respectively. The patient who refused
transplant achieved a complete remission.
Adverse events were consistent with previously reported safety data for
KEYTRUDA. The most common treatment-related adverse events (occurring in
greater than or equal to two patients) included hypothyroidism (n=3),
pneumonitis (n=3), constipation (n=2), diarrhea (n=2), nausea (n=2),
hypercholesterolemia (n=2), hypertriglyceridemia (n=2) and hematuria
(n=2). Sixteen patients (55%) experienced at least one treatment-related
adverse event of any grade. Grade 3 treatment-related adverse events
occurred in a total of three patients and included axillary pain,
hypoxia, joint swelling, and pneumonitis. No Grade 4 treatment-related
adverse events or treatment-related deaths were reported.
About the KEYNOTE-013 Study
KEYNOTE-013 is an ongoing multi-center, non-randomized Phase 1b trial of
approximately 106 patients evaluating the safety, tolerability, and
efficacy of KEYTRUDA monotherapy in patients with blood cancers,
including myelodysplastic syndromes, multiple myeloma, Hodgkin lymphoma,
mediastinal large B cell lymphoma and non-Hodgkin’s lymphoma. The
primary endpoints of the study include overall safety, tolerability, and
complete remission rate (as measured by International Harmonization
Project Response Criteria); secondary endpoints include overall response
rate (ORR), progression-free survival (PFS), overall survival (OS) and
duration of response.
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 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 confirmatory trials.
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
pneumonitis.
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
corticosteroids.
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
diarrhea (20%).
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.
About Lymphoma
Lymphoma is a type of blood cancer that affects the lymphatic system,
which removes excess fluids from the body and produces immune cells.
Abnormal lymphocytes, a type of white blood cell that fight infection,
become lymphoma cells, which multiply and collect in the lymph nodes and
other tissues. Over time, these cancerous cells impair the immune system.1
In 2012, more than 450,000 people were estimated to have been diagnosed
with lymphoma (Hodgkin lymphoma and non-Hodgkin lymphoma); more than
225,000 people died from the condition.2 Hodgkin lymphoma is
different from other lymphomas because it contains Reed-Sternberg cells,
a specific type of large cancer cells.3
About Merck
Today’s Merck is a global healthcare 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 healthcare through
far-reaching policies, programs and partnerships. For more information,
visit www.merck.com
and connect with us on Twitter,
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and YouTube.
Our Focus on Cancer
Our goal is to translate breakthrough science into biomedical
innovations to help people with cancer worldwide. For Merck Oncology,
helping people fight cancer is our passion, supporting accessibility to
our cancer medicines is our commitment, and pursuing research in
immuno-oncology is our focus to potentially bring new hope to people
with cancer. For more information about our oncology clinical trials,
visit www.merck.com/clinicaltrials.
Forward-Looking Statement
This news release includes “forward-looking statements” within the
meaning of the safe harbor provisions of the United States Private
Securities Litigation Reform Act of 1995. These statements are based
upon the current beliefs and expectations of Merck’s management and are
subject to significant risks and uncertainties. There can be no
guarantees with respect to pipeline products that the products will
receive the necessary regulatory approvals or that they will prove to be
commercially successful. If underlying assumptions prove inaccurate or
risks or uncertainties materialize, actual results may differ materially
from those set forth in the forward-looking statements.
Risks and uncertainties include, but are not limited to, general
industry conditions and competition; general economic factors, including
interest rate and currency exchange rate fluctuations; the impact of
pharmaceutical industry regulation and healthcare legislation in the
United States and internationally; global trends toward healthcare cost
containment; technological advances, new products and patents attained
by competitors; challenges inherent in new product development,
including obtaining regulatory approval; Merck’s ability to accurately
predict future market conditions; manufacturing difficulties or delays;
financial instability of international economies and sovereign risk;
dependence on the effectiveness of Merck’s patents and other protections
for innovative products; and the exposure to litigation, including
patent litigation, and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking
statement, whether as a result of new information, future events or
otherwise. Additional factors that could cause results to differ
materially from those described in the forward-looking statements can be
found in Merck’s 2013 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 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.
1 American Society of Hematology. Blood Cancers. Available
at: http://www.hematology.org/Patients/Cancers/.
Accessibility verified on November 3, 2014.
2
GLOBOCAN. World. Available at: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.
Accessibility verified on November 3, 2014.
3 MD
Anderson Cancer Center. Hodgkin’s Lymphoma. Available at: http://www.mdanderson.org/patient-and-cancer-information/cancer-information/cancer-types/hodgkins-lymphoma/index.html.
KEYTRUDA® is a registered trademark of Merck
& Co., Inc., Whitehouse Station, N.J., USA
Media:
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or
Claire Mulhearn, 908-236-1118
or
Investor:
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or
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