Efficacy Data from Phase 2 KEYNOTE-086
Trial, Cohort B, for KEYTRUDA Monotherapy in Patients with
Untreated Metastatic Triple-Negative Breast Cancer to Be Featured
in Spotlight Session
Merck (NYSE: MRK), known as MSD outside the United States and
Canada, today announced that new and updated data from six
abstracts investigating KEYTRUDA® (pembrolizumab), the company’s
anti-PD-1 therapy, as both monotherapy and combination therapy,
across a range of difficult-to-treat breast cancers, will be
presented at the 2017 San Antonio Breast Cancer Symposium (SABCS),
Dec. 5 – 9. In addition to the presentation of KEYTRUDA data at
SABCS, updated data on LYNPARZA® (olaparib), the first-in-class
poly ADP-ribose polymerase (PARP) inhibitor being co-developed and
co-commercialized with AstraZeneca, will be presented.
KEYTRUDA presentations include a Spotlight Session with findings
from the phase 2 KEYNOTE-086 trial, Cohort B, investigating
KEYTRUDA as a monotherapy in previously untreated patients with
metastatic triple-negative breast cancer (TNBC) whose tumors
express PD-L1 (Abstract #PD6-10). In the combination setting,
KEYTRUDA data highlights at SABCS include:
- Final results from the phase 1b/2
KEYNOTE-014 (PANACEA) trial investigating KEYTRUDA in combination
with trastuzumab in trastuzumab-resistant HER2-positive metastatic
breast cancer (Abstract #GS2-06);
- Two new biomarker analyses from the
ongoing phase 2 I-SPY 2 trial (Abstract #PD6-08, Abstract #PD6-14);
and,
- Updated data from the phase 1b/2
KEYNOTE-150 (ENHANCE-1) trial investigating KEYTRUDA
(pembrolizumab) in combination with Eisai Co., Ltd.’s microtubule
dynamics inhibitor, eribulin mesylate (product name: Halaven®,
“eribulin”), in patients with metastatic TNBC (Abstract
#PD6-13).
Data investigating LYNPARZA (olaparib) as monotherapy will also
be presented. Findings include additional data from the pivotal
phase 3 OlympiAD trial investigating LYNPARZA versus chemotherapy
in patients with HER2-negative metastatic breast cancer and a
germline BRCA mutation (Abstract #P5-21-12), as well as a subgroup
analysis in Asian patients (Abstract #P5-21-13).
“We have seen significant therapeutic advances over the years in
the field of breast cancer; however, there remains significant
unmet medical need, particularly in certain categories of the
disease,” said Dr. Roy Baynes, senior vice president and head of
global clinical development, chief medical officer, Merck Research
Laboratories. “Through our comprehensive clinical program studying
KEYTRUDA, as well as LYNPARZA, we hope to bring additional
therapeutic benefit to breast cancer patients.”
A select list of the KEYTRUDA-related abstracts accepted for
presentation at SABCS are included below. For a complete list of
KEYTRUDA and LYNPARZA abstract titles, please visit the SABCS
website.
KEYTRUDA-Related Data at SABCS
Monotherapy Abstracts:
- Abstract #PD6-10 Spotlight Session:
KEYNOTE-086 cohort B: Pembrolizumab monotherapy for PD-L1-positive,
previously untreated, metastatic triple-negative breast cancer
(mTNBC). Adams S. Thursday, Dec. 7. 5:00 p.m. – 7:00 p.m. CT.
Location: Stars at Night Ballroom 3 & 4.
Combination Abstracts:
- Abstract #GS2-06 Oral Presentation:
Phase Ib/II study evaluating safety and efficacy of pembrolizumab
and trastuzumab in patients with trastuzumab-resistant
HER2-positive metastatic breast cancer: Results from the PANACEA
(IBCSG 45-13/BIG 4-13/KEYNOTE-014) study. Loi S. Wednesday, Dec. 6.
4:30 p.m. CT. Location: Hall 3.
- Abstract #PD6-13 Spotlight Session:
Phase 1b/2 study to evaluate eribulin mesylate in combination with
pembrolizumab in patients with metastatic triple-negative breast
cancer. Tolaney SM. Thursday, Dec. 7. 5:00 p.m. – 7:00 p.m. CT.
Location: Stars at Night Ballroom 3 & 4.
- Abstract #PD6-08 Spotlight Session:
Analysis of immune infiltrates (assessed via multiplex fluorescence
immunohistochemistry) and immune gene expression signatures as
predictors of response to the checkpoint inhibitor pembrolizumab in
the neoadjuvant I-SPY 2 trial. Campbell M. Thursday, Dec. 7. 5:00
p.m. – 7:00 p.m. CT. Location: Stars at Night Ballroom 3 &
4.
- Abstract #PD6-14 Spotlight Session:
Analysis of DNA repair deficiency biomarkers as predictors of
response to the PD1 inhibitor pembrolizumab: Results from the
neoadjuvant I-SPY 2 TRIAL for Stage II-III high-risk breast cancer.
Yau C. Thursday, Dec. 7. 5:00 p.m. – 7:00 p.m. CT. Location: Stars
at Night Ballroom 3 & 4.
- Abstract #P1-09-01 Poster Session: A
phase 1b study of abemaciclib plus pembrolizumab for patients with
hormone receptor-positive (HR+), human epidermal growth factor
receptor 2-negative (HER2-) metastatic breast cancer (MBC). Rugo
HS. Wednesday, Dec. 6. 5:00 p.m. – 7:00 p.m. CT. Location: Hall
1.
The KEYTRUDA (pembrolizumab) breast cancer clinical development
program encompasses 15 internal and external collaborative studies
across multiple breast cancer subtypes including four
registration-enabling studies in TNBC (KEYNOTE-119, KEYNOTE-355,
KEYNOTE-242 and KEYNOTE-522), and 11 other studies evaluating
KEYTRUDA either in monotherapy or in combination with other
anti-cancer treatments.
About the AstraZeneca and Merck Strategic Oncology
Collaboration
On July 27, 2017, AstraZeneca and Merck, announced a global
strategic oncology collaboration to co-develop and co-commercialize
AstraZeneca’s LYNPARZA (olaparib), the world’s first PARP
inhibitor, and potential new medicine selumetinib, a MEK inhibitor,
for multiple cancer types. The collaboration is based on increasing
evidence that PARP and MEK inhibitors can be combined with
PD-L1/PD-1 inhibitors for a range of tumor types. Working together,
the companies will jointly develop LYNPARZA and selumetinib in
combination with other potential new medicines and as a
monotherapy. Independently, the companies will develop LYNPARZA and
selumetinib in combination with their respective PD-L1 and PD-1
medicines.
About KEYTRUDA® (pembrolizumab) Injection
100 mg
KEYTRUDA is an anti-PD-1 therapy that works by increasing the
ability of the body’s immune system to help detect and fight tumor
cells. KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody
that 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.
Merck has the industry’s largest immuno-oncology clinical
research program, which currently involves more than 650 trials
studying KEYTRUDA across a wide variety of cancers and treatment
settings. The KEYTRUDA clinical program seeks to understand the
role of KEYTRUDA across cancers and the factors that may predict a
patient’s likelihood of benefitting from treatment with KEYTRUDA,
including exploring several different biomarkers.
KEYTRUDA (pembrolizumab) Indications and Dosing
Melanoma
KEYTRUDA is indicated for the treatment of patients with
unresectable or metastatic melanoma.at a fixed dose of 200 mg every
three weeks until disease progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA, as a single agent, is indicated for the first-line
treatment of patients with metastatic non-small cell lung cancer
(NSCLC) whose tumors have high PD-L1 expression [tumor proportion
score (TPS) ≥50%] as determined by an FDA-approved test, with no
EGFR or ALK genomic tumor aberrations.
KEYTRUDA, as a single agent, is also indicated for the treatment
of patients with metastatic NSCLC whose tumors express PD-L1 (TPS
≥1%) 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.
KEYTRUDA, in combination with pemetrexed and carboplatin, is
indicated for the first-line treatment of patients with metastatic
nonsquamous NSCLC. This indication is approved under accelerated
approval based on tumor response rate and progression-free
survival. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials.
In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of
200 mg every three weeks until disease progression, unacceptable
toxicity, or up to 24 months in patients without disease
progression.
When administering KEYTRUDA (pembrolizumab) in combination with
chemotherapy, KEYTRUDA should be administered prior to chemotherapy
when given on the same day. See also the Prescribing Information
for pemetrexed and carboplatin.
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. 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. In HNSCC, KEYTRUDA is administered at a fixed
dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without
disease progression.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric
patients with refractory classical Hodgkin lymphoma (cHL), or who
have relapsed after three or more prior lines of therapy. 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. In adults with cHL,
KEYTRUDA is administered at a fixed dose of 200 mg every three
weeks until disease progression or unacceptable toxicity, or up to
24 months in patients without disease progression. In pediatric
patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg
(up to a maximum of 200 mg) every three weeks until disease
progression or unacceptable toxicity, or up to 24 months in
patients without disease progression.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma who are not eligible
for cisplatin-containing chemotherapy. This indication is approved
under accelerated approval based on tumor response rate and
duration of response. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
the confirmatory trials.
KEYTRUDA is also indicated for the treatment of patients with
locally advanced or metastatic urothelial carcinoma who have
disease progression during or following platinum-containing
chemotherapy or within 12 months of neoadjuvant or adjuvant
treatment with platinum-containing chemotherapy.
In locally advanced or metastatic urothelial carcinoma, KEYTRUDA
(pembrolizumab) is administered at a fixed dose of 200 mg every
three weeks until disease progression or unacceptable toxicity, or
up to 24 months in patients without disease progression.
Microsatellite Instability-High (MSI-H) Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric
patients with unresectable or metastatic microsatellite
instability-high (MSI-H) or mismatch repair deficient (dMMR)
- 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 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.
In adult patients with MSI-H cancer, KEYTRUDA is administered at
a fixed dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without
disease progression. In children with MSI-H cancer, KEYTRUDA is
administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every
three weeks until disease progression or unacceptable toxicity, or
up to 24 months in patients without disease progression.
Gastric Cancer
KEYTRUDA is indicated for the treatment of patients with
recurrent locally advanced or metastatic gastric or
gastroesophageal junction (GEJ) adenocarcinoma whose tumors express
PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an
FDA-approved test, with disease progression on or after two or more
prior lines of therapy including fluoropyrimidine- and
platinum-containing chemotherapy and if appropriate,
HER2/neu-targeted therapy. 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 recommended dose of KEYTRUDA is 200 mg
every three weeks until disease progression, unacceptable toxicity,
or up to 24 months in patients without disease progression.
Selected Important Safety Information for
KEYTRUDA® (pembrolizumab)
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 discontinue KEYTRUDA.
KEYTRUDA 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. The incidence of new or
worsening hypothyroidism was higher in patients with HNSCC,
occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3
(0.5%) 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 (pembrolizumab) 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.
Immune-mediated rashes, including Stevens-Johnson syndrome
(SJS), toxic epidermal necrolysis (TEN) (some cases with fatal
outcome), exfoliative dermatitis, and bullous pemphigoid, can
occur. Monitor patients for suspected severe skin reactions and
based on the severity of the adverse reaction, withhold or
permanently discontinue KEYTRUDA and administer corticosteroids.
For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer
the patient for specialized care for assessment and treatment. If
SJS or TEN is confirmed, permanently discontinue KEYTRUDA.
KEYTRUDA can cause other clinically important immune-mediated
adverse reactions. These immune-mediated reactions may occur in 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 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%), 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 (pembrolizumab). Treatment with
KEYTRUDA may increase the risk of rejection in solid organ
transplant recipients. Consider the 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 KEYTRUDA.
Immune-mediated complications, including fatal events, occurred
in patients who underwent allogeneic hematopoietic stem cell
transplantation (HSCT) after being treated with KEYTRUDA. Of 23
patients with cHL who proceeded to allogeneic HSCT after treatment
with KEYTRUDA on any trial, 6 patients (26%) developed
graft-versus-host disease (GVHD), one of which was fatal, and 2
patients (9%) developed severe hepatic veno-occlusive disease (VOD)
after reduced-intensity conditioning, one of which was fatal. Cases
of fatal hyperacute GVHD after allogeneic HSCT have also been
reported in patients with lymphoma who received a PD-1
receptor–blocking antibody before transplantation. These
complications may occur despite intervening therapy between PD-1
blockade and allogeneic HSCT. Follow patients closely for early
evidence of transplant-related complications such as hyperacute
GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile
syndrome, hepatic VOD, and other immune-mediated adverse reactions,
and intervene promptly.
In clinical trials in patients with multiple myeloma, the
addition of KEYTRUDA to a thalidomide analogue plus dexamethasone
resulted in increased mortality. Treatment of these patients with a
PD-1 or PD-L1 blocking antibody in this combination is not
recommended outside of controlled clinical trials.
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.
In KEYNOTE-006, KEYTRUDA (pembrolizumab) was discontinued due to
adverse reactions in 9% of 555 patients with advanced melanoma;
adverse reactions leading to discontinuation in more than one
patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic
reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%).
Adverse reactions leading to interruption of KEYTRUDA occurred in
21% of patients; the most common (≥1%) was diarrhea (2.5%). The
most common adverse reactions with KEYTRUDA vs ipilimumab were
fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs
23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates
are listed for ipilimumab only for those adverse reactions that
occurred at the same or lower rate than with KEYTRUDA.
In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to
adverse reactions in 8% of 682 patients with metastatic NSCLC. The
most common adverse event resulting in permanent discontinuation of
KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to
interruption of KEYTRUDA occurred in 23% of patients; the most
common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%),
liver enzyme elevation (1.2%), decreased appetite (1.3%), and
pneumonitis (1%). The most common adverse reactions (occurring in
at least 20% of patients and at a higher incidence than with
docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs
20%), and nausea (20% vs 18%).
In KEYNOTE-021(G1), when KEYTRUDA was administered in
combination with carboplatin and pemetrexed (carbo/pem) in advanced
nonsquamous NSCLC, KEYTRUDA was discontinued in 10% of 59 patients.
The most common adverse reaction resulting in discontinuation of
KEYTRUDA (≥2%) was acute kidney injury (3.4%). Adverse reactions
leading to interruption of KEYTRUDA occurred in 39% of patients;
the most common (≥2%) were fatigue (8%), neutrophil count decreased
(8%), anemia (5%), dyspnea (3.4%), and pneumonitis (3.4%).The most
common adverse reactions (≥20%) with KEYTRUDA compared to carbo/pem
alone were fatigue (71% vs 50%), nausea (68% vs 56%), constipation
(51% vs 37%), rash (42% vs 21%), vomiting (39% vs 27%), dyspnea
(39% vs 21%), diarrhea (37% vs 23%), decreased appetite (31% vs
23%), headache (31% vs 16%), cough (24% vs 18%), dizziness (24% vs
16%), insomnia (24% vs 15%), pruritus (24% vs 4.8%), peripheral
edema (22% vs 18%), dysgeusia (20% vs 11%), alopecia (20% vs 3.2%),
upper respiratory tract infection (20% vs 3.2%), and arthralgia
(15% vs 24%). This study was not designed to demonstrate a
statistically significant difference in adverse reaction rates for
KEYTRUDA as compared to carbo/pem alone for any specified adverse
reaction.
In KEYNOTE-012, KEYTRUDA was discontinued due to adverse
reactions in 17% of 192 patients with HNSCC. Serious adverse
reactions occurred in 45% of patients. The most frequent serious
adverse reactions reported in at least 2% of patients were
pneumonia, dyspnea, confusional state, vomiting, pleural effusion,
and respiratory failure. The most common adverse reactions
(reported in at least 20% of patients) were fatigue, decreased
appetite, and dyspnea. Adverse reactions occurring in patients with
HNSCC were generally similar to those occurring in patients with
melanoma or NSCLC, with the exception of increased incidences of
facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or
worsening hypothyroidism.
In KEYNOTE-087, KEYTRUDA (pembrolizumab) was discontinued due to
adverse reactions in 5% of 210 patients with cHL, and treatment was
interrupted due to adverse reactions in 26% of patients. Fifteen
percent (15%) of patients had an adverse reaction requiring
systemic corticosteroid therapy. Serious adverse reactions occurred
in 16% of patients. The most frequent serious adverse reactions
(≥1%) included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and
herpes zoster. Two patients died from causes other than disease
progression; one from GVHD after subsequent allogeneic HSCT and one
from septic shock. The most common adverse reactions (occurring in
≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%),
musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
In KEYNOTE-052, KEYTRUDA was discontinued due to adverse
reactions in 11% of 370 patients with locally advanced or
metastatic urothelial carcinoma. The most common adverse reactions
(in ≥20% of patients) were fatigue (38%), musculoskeletal pain
(24%), decreased appetite (22%), constipation (21%), rash (21%),
and diarrhea (20%). Eighteen patients (5%) died from causes other
than disease progression. Five patients (1.4%) who were treated
with KEYTRUDA experienced sepsis which led to death, and 3 patients
(0.8%) experienced pneumonia which led to death. Adverse reactions
leading to interruption of KEYTRUDA occurred in 22% of patients;
the most common (≥1%) were liver enzyme increase, diarrhea, urinary
tract infection, acute kidney injury, fatigue, joint pain, and
pneumonia. Serious adverse reactions occurred in 42% of patients,
the most frequent (≥2%) of which were urinary tract infection,
hematuria, acute kidney injury, pneumonia, and urosepsis.
In KEYNOTE-045, KEYTRUDA was discontinued due to adverse
reactions in 8% of 266 patients with locally advanced or metastatic
urothelial carcinoma. The most common adverse reaction resulting in
permanent discontinuation of KEYTRUDA was pneumonitis (1.9%).
Adverse reactions leading to interruption of KEYTRUDA occurred in
20% of patients; the most common (≥1%) were urinary tract infection
(1.5%), diarrhea (1.5%), and colitis (1.1%). The most common
adverse reactions (≥20%) in patients who received KEYTRUDA vs those
who received chemotherapy were fatigue (38% vs 56%),
musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%), decreased
appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs 13%).
Serious adverse reactions occurred in 39% of KEYTRUDA-treated
patients, the most frequent (≥2%) of which were urinary tract
infection, pneumonia, anemia, and pneumonitis.
It is not known whether KEYTRUDA (pembrolizumab) 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.
There is limited experience in pediatric patients. In a study,
40 pediatric patients (16 children aged 2 years to younger than 12
years and 24 adolescents aged 12 years to 18 years) with advanced
melanoma, lymphoma, or PD-L1–positive advanced, relapsed, or
refractory solid tumors were administered KEYTRUDA 2 mg/kg every 3
weeks. Patients received KEYTRUDA for a median of 3 doses (range
1–17 doses), with 34 patients (85%) receiving KEYTRUDA for 2 doses
or more. The safety profile in these pediatric patients was similar
to that seen in adults treated with KEYTRUDA. Toxicities that
occurred at a higher rate (≥15% difference) in these patients when
compared to adults under 65 years of age were fatigue (45%),
vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%),
and hyponatremia (18%).
About LYNPARZA® (olaparib)
LYNPARZA was the first FDA-approved oral poly ADP-ribose
polymerase (PARP) inhibitor that may exploit tumor DNA damage
response (DDR) pathway deficiencies to potentially kill cancer
cells. Specifically, in vitro studies have shown that
olaparib-induced cytotoxicity may involve inhibition of PARP
enzymatic activity and increased formation of PARP-DNA complexes,
resulting in DNA damage and cancer cell death.
IMPORTANT SAFETY INFORMATION FOR LYNPARZA®
(olaparib)
DOSING AND ADMINISTRATION
To avoid substitution errors and overdose, do not substitute
LYNPARZA tablets with LYNPARZA capsules on a
milligram-to-milligram basis due to differences in the dosing and
bioavailability of each formulation. Recommended tablet dose is 300
mg, taken orally twice daily, with or without food. Continue
treatment until disease progression or unacceptable toxicity. For
adverse reactions, consider dose interruption or dose
reduction.
WARNINGS AND PRECAUTIONS
There are no contraindications for LYNPARZA.
Myelodysplastic Syndrome/Acute Myeloid Leukemia
(MDS/AML): Occurred in <1.5% of patients exposed to
LYNPARZA (olaparib) monotherapy, and the majority of events had a
fatal outcome. The duration of therapy in patients who developed
secondary MDS/AML varied from <6 months to >2 years. All of
these patients had previous chemotherapy with platinum agents
and/or other DNA-damaging agents, including radiotherapy, and some
of these patients also had a history of previous cancer or bone
marrow dysplasia.
Do not start LYNPARZA until patients have recovered from
hematological toxicity caused by previous chemotherapy (≤Grade 1).
Monitor complete blood counts for cytopenia at baseline and monthly
thereafter for clinically significant changes during treatment. For
prolonged hematological toxicities, interrupt LYNPARZA and monitor
blood counts weekly until recovery. If the levels have not
recovered to Grade 1 or less after 4 weeks, refer the patient to a
hematologist for further investigations, including bone marrow
analysis and blood sample for cytogenetics. Discontinue LYNPARZA if
MDS/AML is confirmed.
Pneumonitis: Occurred in <1% of patients exposed
to LYNPARZA, and some cases were fatal. If patients present with
new or worsening respiratory symptoms such as dyspnea, cough, and
fever, or a radiological abnormality occurs, interrupt treatment
with LYNPARZA and initiate prompt investigation. Discontinue
LYNPARZA if pneumonitis is confirmed and treat patient
appropriately.
Embryo-Fetal Toxicity: Based on its mechanism of
action and findings in animals, LYNPARZA can cause fetal harm. A
pregnancy test is recommended for females of reproductive potential
prior to initiating treatment. Advise females of reproductive
potential of the potential risk to a fetus and to use effective
contraception during treatment and for 6 months after receiving the
final dose.
ADVERSE REACTIONS—Maintenance Setting
Most common adverse reactions (Grades 1-4) in ≥20% of patients
in clinical trials of LYNPARZA in the maintenance
setting for SOLO-2: nausea (76%), fatigue
(including asthenia) (66%), anemia (44%), vomiting (37%),
nasopharyngitis/upper respiratory tract infection (URI)/influenza
(36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%),
headache (26%), decreased appetite (22%), and stomatitis (20%).
Study 19: nausea (71%), fatigue (including asthenia)
(63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory
tract infection (22%), constipation (22%), headache (21%), and
decreased appetite (21%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients in clinical trials of LYNPARZA (olaparib) in
the maintenance setting (SOLO-2/Study 19) were:
increase in mean corpuscular volume (89%/82%), decrease in
hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in
lymphocytes (67%/52%), decrease in absolute neutrophil count
(51%/47%), increase in serum creatinine (44%/45%), and decrease in
platelets (42%/36%).
ADVERSE REACTIONS—Advanced gBRCAm ovarian cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients
in clinical trials of LYNPARZA for advanced gBRCAm ovarian
cancer after 3 or more lines of chemotherapy (pooled from 6
studies) were: fatigue (including asthenia) (66%), nausea (64%),
vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper
respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia
(22%), decreased appetite (22%), and arthralgia/musculoskeletal
pain (21%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients in clinical trials of LYNPARZA for advanced gBRCAm
ovarian cancer after 3 or more lines of chemotherapy (pooled
from 6 studies) were: decrease in hemoglobin (90%), increase in
mean corpuscular volume (57%), decrease in lymphocytes (56%),
increase in serum creatinine (30%), decrease in platelets (30%),
and decrease in absolute neutrophil count (25%).
DRUG INTERACTIONS
Anticancer Agents: Clinical studies of LYNPARZA in
combination with other myelosuppressive anticancer agents,
including DNA-damaging agents, indicate a potentiation and
prolongation of myelosuppressive toxicity.
CYP3A Inhibitors: Avoid concomitant use of strong or
moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor
must be co-administered, reduce the dose of LYNPARZA. Advise
patients to avoid grapefruit, grapefruit juice, Seville oranges,
and Seville orange juice during LYNPARZA treatment.
CYP3A Inducers: Avoid concomitant use of strong or
moderate CYP3A inducers when using LYNPARZA. If a moderate inducer
cannot be avoided, be aware of a potential for decreased efficacy
of LYNPARZA.
USE IN SPECIFIC POPULATIONS
Pediatric Use: The safety and efficacy of LYNPARZA
(olaparib) have not been established in pediatric patients.
Lactation: No data are available regarding the
presence of olaparib in human milk, the effects on the breastfed
infant, or the effects on milk production. Because of the potential
for serious adverse reactions in the breastfed infant, advise a
lactating woman not to breastfeed during treatment with LYNPARZA
and for 1 month after receiving the final dose.
Hepatic Impairment: No adjustment to the starting
dose is required in patients with mild hepatic impairment
(Child-Pugh classification A). There are no data in patients with
moderate or severe hepatic impairment.
Renal Impairment: No adjustment to the starting dose
is necessary in patients with mild renal impairment (CLcr
51-80 mL/min). In patients with moderate renal
impairment (CLcr 31-50 mL/min), reduce the dose to 200 mg
twice daily. There are no data in patients with severe renal
impairment or end-stage renal disease (CLcr ≤30
mL/min).
APPROVED USES for LYNPARZA (olaparib)
LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor
indicated:
- For the maintenance treatment of adult
patients with recurrent epithelial ovarian, fallopian tube, or
primary peritoneal cancer, who are in complete or partial response
to platinum-based chemotherapy
- For the treatment of adult patients
with deleterious or suspected deleterious germline BRCA-mutated
(gBRCAm) advanced ovarian cancer who have been treated with 3 or
more prior lines of chemotherapy. Select patients for therapy based
on an FDA-approved companion diagnostic for LYNPARZA
Merck’s Focus on Cancer
Our goal is to translate breakthrough science into innovative
oncology medicines to help people with cancer worldwide. At Merck,
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 with cancer.
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 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.
About Merck
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,
visit www.merck.com and connect with us on
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and LinkedIn.
Forward-Looking Statement of Merck & Co., Inc.,
Kenilworth, N.J., USA
This news release of Merck & Co., Inc., Kenilworth, N.J.,
USA (the “company”) includes “forward-looking statements” within
the meaning of the safe harbor provisions of the U.S. Private
Securities Litigation Reform Act of 1995. These statements are
based upon the current beliefs and expectations of the company’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 health care
legislation in the United States and internationally; global trends
toward health care cost containment; technological advances, new
products and patents attained by competitors; challenges inherent
in new product development, including obtaining regulatory
approval; the company’s ability to accurately predict future market
conditions; manufacturing difficulties or delays; financial
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dependence on the effectiveness of the company’s patents and other
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The company undertakes no obligation to publicly update any
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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 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 http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf
and Patient Information/Medication Guide for KEYTRUDA
at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.
Please see complete Prescribing Information
for LYNPARZA, including Patient Information (Medication
Guide)
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MerckMedia:Pamela Eisele,
267-305-3558orAnn Bush, 908-740-6677orInvestors:Teri Loxam, 908-740-1986orMichael
DeCarbo, 908-740-1807
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