KEYTRUDA® (pembrolizumab) in Combination with Inlyta® (axitinib) Reduced Risk of Death by Nearly Half Compared to Sunitinib as First-Line Treatment for Advanced Renal Cell Carcinoma (RCC)

Results from Phase 3 KEYNOTE-426 Study Presented Today at the 2019
Genitourinary Cancers Symposium (ASCO GU) and Published in the New
England Journal of Medicine
Also Showed Risk of Progression or Death
Reduced by 31 Percent

Data Consistent Across all IMDC Risk Groups and Regardless of PD-L1
Expression

KENILWORTH, N.J.–(BUSINESS WIRE)–lt;a href=”https://twitter.com/search?q=%24MRK&src=ctag” target=”_blank”gt;$MRKlt;/agt; lt;a href=”https://twitter.com/hashtag/Keytruda?src=hash” target=”_blank”gt;#Keytrudalt;/agt;–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced presentation of the full results from the pivotal Phase
3 KEYNOTE-426 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy,
in combination with Inlyta (axitinib), a tyrosine kinase inhibitor, for
the first-line treatment of advanced renal cell carcinoma (RCC) at the
2019 Genitourinary Cancers Symposium (ASCO GU) (Abstract #543). These
data were also simultaneously published in the New England Journal of
Medicine
. This is the first combination regimen to significantly
improve overall survival (OS), progression-free survival (PFS) and
objective response rate (ORR) compared to sunitinib. Results were
consistent across all IMDC subgroups, including favorable, intermediate
and poor risk groups, and regardless of PD-L1 expression.

As previously announced, the U.S. Food and Drug Administration (FDA) has
granted priority review for a supplemental Biologics License Application
(sBLA) for KEYTRUDA in combination with axitinib for the first-line
treatment of patients with advanced RCC based on the results of
KEYNOTE-426, and has set a Prescription Drug User Fee Act (PDUFA), or
target action, date of June 20, 2019.

Historically, patients with advanced RCC have faced five-year survival
rates of less than 10 percent. Given the aggressive nature of this
disease and the poor long-term prognosis, these new survival data with
KEYTRUDA in combination with axitinib from KEYNOTE-426 offer the
potential of a new treatment option for patients with advanced renal
cell carcinoma,” said Dr. Thomas Powles, lead investigator for
KEYNOTE-426, professor of genitourinary oncology, lead for Solid Tumor
Research at Barts Cancer Institute, director of Barts Cancer Centre.

Findings from the first interim analysis showed KEYTRUDA in combination
with axitinib reduced the risk of death by 47 percent – significantly
improving OS compared to sunitinib (HR=0.53 [95% CI, 0.38-0.74];
p<0.0001). For the dual primary endpoint of PFS, the KEYTRUDA combination showed a reduction in the risk of progression of disease or death of 31 percent compared to sunitinib (HR=0.69 [95% CI, 0.57-0.84]; p=0.0001). In the study, the ORR was 59.3 percent for patients who received KEYTRUDA in combination with axitinib (95% CI, 54.5-63.9) and 35.7 percent for those who received sunitinib (95% CI, 31.1-40.4) (p<0.0001), with a complete response rate of 5.8 percent (n=25) and 1.9 percent (n=8) and a partial response rate of 53.5 percent (n=231) and 33.8 percent (n=145), for patients receiving the KEYTRUDA combination or sunitinib, respectively. Median duration of response was not reached in the KEYTRUDA combination arm (range, 1.4+ to 18.2+ months) and was 15.2 months (range, 1.1+ to 15.4+) in the sunitinib arm. The results for OS, PFS and ORR were consistent across all IMDC risk groups and seen regardless of PD-L1 expression. The observed adverse event profile was as expected based on the known profiles of KEYTRUDA and axitinib. There was a higher incidence of grade 3 or 4 liver enzyme elevation with KEYTRUDA plus axitinib than previously observed with each agent as monotherapy.

With a reduction in the risk of death by nearly half, these findings
are particularly impressive considering the benefit was not limited to
one subgroup of patients – we observed an overall survival improvement
across all IMDC risk groups and regardless of PD-L1 expression,” said
Dr. Roy Baynes, senior vice president and head of global clinical
development, chief medical officer, Merck Research Laboratories. “We are
pleased that these findings have been accepted for priority review by
the FDA, and hopeful that they will be viewed positively by regulatory
authorities worldwide. In the meantime, we are grateful to the
investigators and patients for their involvement in this important
study.”

These data build on the single-agent activity of pembrolizumab and
axitinib, and represent the first time a kidney cancer regimen has
improved overall survival, progression-free survival and objective
response rate versus sunitinib. More importantly, they offer patients
with this aggressive form of kidney cancer a potential new first-line
treatment option,” said Dr. Brian Rini, lead author for the New
England Journal of Medicine
publication of KEYNOTE-426, medical
oncologist at Cleveland Clinic Cancer Center and professor of medicine
at the Cleveland Clinic Lerner College of Medicine of Case Western
Reserve University. As reported by the Cleveland Clinic, Dr. Rini
reports consulting and research funding from Merck.

Merck has filed these data with regulatory authorities worldwide. Merck
has an extensive clinical development program in RCC and is advancing
multiple potential registration-enabling studies with KEYTRUDA, as
monotherapy and in combination with other treatments, including
KEYNOTE-564 and KEYNOTE-581.

Study Design and Additional Data from KEYNOTE-426

KEYNOTE-426 is a randomized, double-arm, Phase 3 trial
(ClinicalTrials.gov, NCT02853331) evaluating the safety and efficacy of
KEYTRUDA in combination with axitinib as first-line treatment for
advanced or metastatic RCC compared to sunitinib monotherapy. The dual
primary endpoints of the study were OS and PFS; key secondary endpoints
include ORR, safety, duration of response, PFS at 12, 18 and 24 months
and OS at 12, 18 and 24 months. The primary outcome measures were
further evaluated based on PD-L1 tumor expression (combined positive
score [CPS] <1 [n=325] and ≥1 [n=497]). In the trial, 861 patients determined to be favorable-, intermediate- or poor-risk by IMDC criteria (n=269, n=484, n=108, respectively) were randomly assigned to receive KEYTRUDA 200 mg intravenously every three weeks plus axitinib 5 mg orally twice daily for up to 24 months (n=432), or sunitinib 50 mg orally once daily for four weeks followed by no treatment for two weeks (n=429).

At the first interim analysis, after a median follow-up of 12.8 months,
overall survival was significantly longer in the KEYTRUDA combination
arm than in the sunitinib arm (HR=0.53 [95% CI, 0.38-0.74]; p<0.0001). Estimated 12-month survival rates were 89.9 percent (95% CI, 86.4-92.4) in the KEYTRUDA combination arm compared to 78.3 percent (95% CI, 73.8-82.1) in the sunitinib arm; the 18-month survival estimates were 82.3 percent (95% CI, 77.2-86.3) and 72.1 percent (95% CI, 66.3-77.0), respectively. Median survival was not reached in either group. Progression-free survival was also significantly longer in the KEYTRUDA combination arm than in the sunitinib arm (HR=0.69 [95% CI, 0.57-0.84]; p=0.0001). The 12-month PFS rate was 59.6 percent in the KEYTRUDA combination arm and 46.2 percent in the sunitinib arm; the 18-month PFS rate was 41.1 percent in the KEYTRUDA combination arm and 32.9 percent in the sunitinib arm. Median PFS was 15.1 months (95% CI, 12.6-17.7) in the KEYTRUDA combination arm compared to 11.1 months (95% CI, 8.7-12.5) in the sunitinib arm.

Analysis of the OS endpoint based on patient subgroups showed consistent
results across each of the IMDC risk categories (favorable, intermediate
and poor) (HR=0.64 [95% CI, 0.24-1.68]; HR=0.53 [95% CI, 0.35-0.82]; and
HR=0.43 [95% CI, 0.23-0.81], respectively), and regardless of PD-L1
expression (PD-L1 combined positive score [CPS <1 [HR=0.59 (95% CI, 0.34-1.03)] and PD-L1 CPS ≥1 [HR=0.54 (95% CI, 0.35-0.84]). Results were also consistent for PFS across these same IMDC risk categories (HR=0.81 [95% CI, 0.53-1.24]; HR=0.70 [95% CI, 0.54-0.91]; and HR=0.58 [95% CI, 0.35-0.94], respectively), as well as for tumors with PD-L1 CPS <1 (HR=0.87 [95% CI, 0.62-1.23]) and PD-L1 CPS ≥1 (HR=0.62 [95% CI, 0.47-0.80]). Subgroup analyses were not controlled for multiplicity.

Grade 3-5 treatment-related adverse events (TRAEs) occurred in 62.9
percent of the 429 treated patients in the KEYTRUDA combination arm and
58.1 percent of the 425 treated patients in the sunitinib arm. TRAEs
resulting in discontinuation of any treatment occurred in 25.9 percent
of patients in the KEYTRUDA combination arm and 10.1 percent of patients
in the sunitinib arm; 8.2 percent of patients discontinued both KEYTRUDA
and axitinib. The most common grade 3-5 TRAEs (occurring in ≥10% of
patients) were hypertension (22.1%) and increased alanine
aminotransferase (ALT) (13.3%) in the KEYTRUDA combination arm and
hypertension (19.3%) in the sunitinib arm.

Immune-mediated adverse events and infusion reactions of any grade
occurred in 51.3 percent of patients in the KEYTRUDA combination arm and
36.2 percent of patients in the sunitinib arm. The most common
immune-mediated adverse events (occurring in ≥10% of patients) were
hypothyroidism (35.4%) and hyperthyroidism (12.8%) in the KEYTRUDA
combination arm and hypothyroidism (31.5%) in the sunitinib arm.
Treatment-related deaths occurred in four patients in the KEYTRUDA
combination arm (myasthenia gravis, myocarditis, necrotizing fasciitis,
pneumonitis [n=1 each]), and seven patients in the sunitinib arm (acute
myocardial infarction, cardiac arrest, fulminant hepatitis,
gastrointestinal hemorrhage, intracranial hemorrhage, malignant neoplasm
progression, pneumonia [n=1 each]).

About Renal Cell Carcinoma (RCC)

Renal cell carcinoma is by far the most common type of kidney cancer;
about 9 out of 10 kidney cancers are RCCs. Renal cell carcinoma is about
twice as common in men as in women. Modifiable risk factors include
smoking, obesity, workplace exposure to certain substances and high
blood pressure. There were approximately 403,000 cases of kidney cancer
diagnosed worldwide in 2018 and about 175,000 deaths from the disease.
In the U.S. alone, there will be an estimated 74,000 new cases of kidney
cancer diagnosed in 2019 and about 15,000 people will die from the
disease.

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.

Merck has the industry’s largest immuno-oncology clinical research
program. There are currently more than 900 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, in combination with pemetrexed and platinum chemotherapy, is
indicated for the first-line treatment of patients with metastatic
nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK
genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or
nab-paclitaxel, is indicated for the first-line treatment of patients
with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment
of patients with metastatic 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 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.

In metastatic NSCLC, the recommended dose of KEYTRUDA is 200 mg
administered as an intravenous infusion over 30 minutes 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 the chemotherapy agents
administered in combination with KEYTRUDA, as appropriate.

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 as an intravenous infusion over 30 minutes 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 3 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 as an
intravenous infusion over 30 minutes 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 as an intravenous infusion over 30 minutes 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.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients
with refractory primary mediastinal large B-cell lymphoma (PMBCL), or
who have relapsed after 2 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 confirmatory trials. KEYTRUDA is not recommended for
the treatment of patients with PMBCL who require urgent cytoreductive
therapy.

In adults with PMBCL, KEYTRUDA is administered as an intravenous
infusion over 30 minutes 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 PMBCL, KEYTRUDA
is administered as an intravenous infusion over 30 minutes 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 (mUC) who are not eligible
for cisplatin-containing chemotherapy and whose tumors express PD-L1
[Combined Positive Score (CPS) ≥10] as determined by an FDA-approved
test, or in patients who are not eligible for any platinum-containing
chemotherapy regardless of PD-L1 status. 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 indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma (mUC) 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 as an intravenous infusion over 30 minutes 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 as an
intravenous infusion over 30 minutes 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 as an intravenous infusion over 30 minutes 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 an intravenous
infusion over 30 minutes of 200 mg every three weeks until disease
progression, unacceptable toxicity, or up to 24 months in patients
without disease progression.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or
metastatic cervical cancer with disease progression on or after
chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an
FDA-approved test. 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 an intravenous infusion over
30 minutes of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without disease
progression.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular
carcinoma (HCC) who have been previously treated with sorafenib. 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 an intravenous infusion over 30 minutes of 200 mg every
three weeks until disease progression, unacceptable toxicity, or up to
24 months in patients without disease progression.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients
with recurrent locally advanced or metastatic Merkel cell carcinoma.
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 in adults is 200 mg administered as an intravenous infusion
over 30 minutes every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without disease
progression. The recommended dose of KEYTRUDA in pediatric patients is 2
mg/kg (up to a maximum of 200 mg), administered as an intravenous
infusion over 30 minutes 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

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases.
Pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA,
including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%),
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.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7%
(48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3
(1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7%
(19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3
(0.4%), and 4 (<0.1%). 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.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause hypophysitis, thyroid disorders, and type 1 diabetes
mellitus. Hypophysitis occurred in 0.6% (17/2799) of patients, including
Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in patients with HNSCC, occurring in 15% (28/192) of patients. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.

Contacts

Media:
Pamela Eisele
(267) 305-3558

Elizabeth H.
Sell
(267) 305-3877

Investors:
Teri Loxam
(908)
740-1986

Peter Dannenbaum
(908) 740-1037

Read full story here