Market Overview

New and Updated Data for KEYTRUDA® (pembrolizumab) from Merck's Extensive Immuno-Oncology Program to be Presented at the ESMO 2017 Congress

Share:

Broad Set of Data for KEYTRUDA in 12 Types of Cancer as Monotherapy
and in Combination to be Presented

Data Include Additional Results from KEYNOTE-021G in Non-Small Cell
Lung Cancer and First Presentation of Results from KEYNOTE-040 in
Advanced Head and Neck Squamous Cell Carcinoma

Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced that studies involving KEYTRUDA®
(pembrolizumab), the company's anti-PD-1 therapy, in 12 different types
of cancer will be presented at the European Society for Medical Oncology
(ESMO) 2017 Congress in Madrid, Spain, Sept. 8-12. In total, 35
abstracts – including data from studies investigating the use of
KEYTRUDA as monotherapy and in novel combinations – were accepted for
presentation at the congress, including five late-breaking
abstracts. Data to be presented include studies of KEYTRUDA as
monotherapy in advanced urothelial (bladder) carcinoma, gastric cancer,
head and neck squamous cell carcinoma (HNSCC), microsatellite
instability-high (MSI-H) or mismatch repair deficient cancer and
triple-negative breast cancer (TNBC), as well as studies of KEYTRUDA in
combination with other therapies in advanced non-small cell lung cancer
(NSCLC), gastric cancer and melanoma.

Merck's broad KEYTRUDA clinical development program includes more than
30 tumor types in more than 550 clinical trials, including more than 300
trials that combine KEYTRUDA with other cancer treatments.

In addition to the data for KEYTRUDA to be presented at ESMO,
researchers will also present data for LYNPARZA®
(olaparib), including the SOLO-2 and OlympiAD trials. For more
information, including a complete list of KEYTRUDA (pembrolizumab) and
LYNPARZA (olaparib) abstract titles, please see the ESMO program at https://cslide.ctimeetingtech.com/library/esmo/browse/search/Fag.

Late-Breaking KEYTRUDA Abstracts
In
total, five KEYTRUDA abstracts were selected as late-breaking abstracts.
In lung cancer, an additional five-months of follow-up from the phase 2
KEYNOTE-021 trial, Cohort G, which is studying KEYTRUDA in combination
with pemetrexed/carboplatin for the first-line treatment of NSCLC, will
be presented. Three abstracts will be featured in the official ESMO
press program, including results for KEYTRUDA in advanced gastric
cancer, as monotherapy and in combination therapy, from the multi-cohort
phase 2 KEYNOTE-059 trial; longer-term overall survival data for
KEYTRUDA versus chemotherapy for urothelial carcinoma from the phase 3
KEYNOTE-045 trial; and, the first-time presentation of data for KEYTRUDA
monotherapy in previously treated patients with recurrent or metastatic
HNSCC from the phase 3 KEYNOTE-040 trial.

Further information on late-breaking abstracts for KEYTRUDA:

  • NSCLC: (Abstract #LBA49) Proffered Paper Session: Updated
    results from KEYNOTE-021 cohort G: a randomized, phase 2 study of
    pemetrexed and carboplatin (PC) with or without pembrolizumab (pembro)
    as first-line therapy for advanced nonsquamous NSCLC. H. Borghaei.
    Friday, Sept. 8, 5:03 – 5:15 p.m. CEST. Location: Madrid Auditorium.
  • Gastric Cancer: (Abstract #LBA28_PR) Proffered Paper Session:
    KEYNOTE-059 update: efficacy and safety of pembrolizumab alone or in
    combination with chemotherapy in patients with advanced gastric or
    gastroesophageal (G/GEJ) cancer. Z. A. Wainberg. Friday, Sept. 8, 3:03
    – 3:15 p.m. CEST. Location: Barcelona Auditorium.
  • Urothelial Carcinoma: (Abstract #LBA37_PR) Poster Discussion
    Session: Pembrolizumab (pembro) versus paclitaxel, docetaxel, or
    vinflunine for recurrent, advanced urothelial cancer (UC): mature
    results from the phase 3 KEYNOTE-045 trial. R. De Wit. Sunday, Sept.
    10 Poster: 2:45 – 4:15 p.m. CEST. Discussion: 3:15 – 3:45 p.m. CEST.
    Location: Cordoba Auditorium.
  • HNSCC: (Abstract #LBA45_PR) Proffered Paper Session:
    Pembrolizumab (pembro) vs standard of care (SOC) for recurrent or
    metastatic head and neck squamous cell carcinoma (R/M HNSCC): Phase 3
    KEYNOTE-040 trial. E. E. Cohen. Monday, Sept. 11, 3:00 – 3:12 p.m.
    CEST. Location: Granada Auditorium.
  • Breast Cancer: (Abstract #LBA13) Proffered Paper Session:
    Relationship between tumor infiltrating lymphocyte (TIL) levels and
    response to pembrolizumab (pembro) in metastatic triple-negative
    breast cancer (mTNBC): results from KEYNOTE-086. S. Loi. Saturday,
    Sept. 9, 11:45 – 12:00 p.m. CEST. Location: Madrid Auditorium.

Additional KEYTRUDA (pembrolizumab) Abstracts
Combination
data at ESMO include findings from the phase 1/2 ECHO-202/KEYNOTE-037
trial of KEYTRUDA in combination with epacadostat, Incyte's
investigational oral selective IDO1 enzyme inhibitor, in advanced
melanoma, as well as findings from the phase 1b/2 trial of KEYTRUDA with
Eisai's multiple receptor tyrosine kinase inhibitor, Lenvima®
(lenvatinib), in advanced renal cell carcinoma. Monotherapy data include
findings from the phase 1 KEYNOTE-028 trial studying KEYTRUDA in PD-L1
positive advanced carcinoid or pancreatic cancer and findings from the
KEYNOTE-164 and KEYNOTE-158 studies of KEYTRUDA in MSI-H cancers.

Further information on select KEYTRUDA abstracts:

  • Renal Cell Cancer: (Abstract #847O) Proffered Paper Session: A
    Phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with
    renal cell carcinoma. C. Lee. Saturday, Sept. 9, 10:15 – 10:30 a.m.
    CEST. Location: Madrid Auditorium.
  • Melanoma: (Abstract #1214O) Proffered Paper Session:
    Epacadostat plus pembrolizumab in patients with advanced melanoma:
    phase 1 and 2 efficacy and safety results from ECHO-202/KEYNOTE-037.
    O. Hamid. Saturday, Sept. 9, 3:00 – 3:15 p.m. CEST. Location: Madrid
    Auditorium.
  • Melanoma: (Abstract #1216O) Proffered Paper Session:
    KEYNOTE-022 update: phase 1 study of first-line pembrolizumab (pembro)
    plus dabrafenib (D) and trametinib (T) for BRAF-mutant advanced
    melanoma. A. Ribas. Saturday, Sept. 9, 3:45 – 4:00 p.m. CEST.
    Location: Madrid Auditorium.
  • Pancreatic Cancer: (Abstract #427O) Proffered Paper Session:
    Pembrolizumab for patients with PD-L1–positive advanced carcinoid or
    pancreatic neuroendocrine tumors: results from the KEYNOTE-028 study.
    J. M. Mehnert. Sunday, Sept. 10, 4:30 – 4:42 p.m. CEST. Location:
    Tarragona Auditorium.
  • Advanced MSI-H Cancer: (Abstract #386P) Poster Display Session:
    Efficacy of pembrolizumab in phase 2 KEYNOTE-164 and KEYNOTE-158
    studies of microsatellite instability high cancers. L. Diaz. Monday,
    Sept. 11, 1:15 – 2:15 p.m. CEST. Location: Hall 8.

About the AstraZeneca and Merck Strategic Oncology Collaboration
On
July 27, 2017, AstraZeneca and Merck & Co., Inc. announced a global
strategic oncology collaboration to co-develop and co-commercialize
AstraZeneca's LYNPARZA, 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 PDL-1/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
100mg

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 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.

Studies of KEYTRUDA – from the largest immuno-oncology program in the
industry with more than 550 trials – include a wide variety of cancers
and treatment settings. The KEYTRUDA clinical program seeks to
understand factors that predict a patient's likelihood of benefitting
from treatment with KEYTRUDA, including the exploration of several
different biomarkers across a broad range of tumors.

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 (pembrolizumab), 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 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 (pembrolizumab) 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 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
pediatric patients 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.

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 (5%) hypothyroidism. Thyroiditis occurred
in 16 (0.6%) of 2799 patients receiving KEYTRUDA (pembrolizumab),
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 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 and 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.

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 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 (pembrolizumab) 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.

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%).

When KEYTRUDA was administered in combination with carboplatin and
pemetrexed (carbo/pem), 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.

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.

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-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.

The most common adverse reactions (reported in ≥ 20% patients) were
fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough,
dyspnea, musculoskeletal pain, constipation and nausea.

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.

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.

LYNPARZA (olaparib) tablets are currently being investigated in
combinations in a range of tumor types, including breast, prostate, and
pancreatic cancer.

LYNPARZA capsules (400mg twice daily) will still be available through a
limited specialty pharmacy network, for patients currently being treated
for deleterious or suspected deleterious germline BRCA-mutated advanced
ovarian cancer who have been treated with three or more prior lines of
chemotherapy. LYNPARZA tablets and capsules are not the same.

If you have been prescribed LYNPARZA tablets, do not take the capsules.
If you have any questions about LYNPARZA, please talk with your
physician or pharmacist.

LYNPARZA Important Safety Information

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 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 (olaparib) 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 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 (olaparib) 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
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 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

Our 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 that includes more than 550 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.

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 TwitterFacebookInstagram,
YouTube
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 instability of international economies and
sovereign risk; dependence on the effectiveness of the company's patents
and other protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory actions.

The company 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 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 (olaparib), including Patient
Information (Medication Guide).

View Comments and Join the Discussion!