Merck Increases Focus on Advanced Prostate Cancer, Expanding Immuno-Oncology Program with Three New Phase 3 Trials

Research Program Expanded Based on Promising Data Shown with KEYTRUDA®
(pembrolizumab) in Combination with LYNPARZA
®
(olaparib), Chemotherapy and Anti-Hormone Agents in Patients with
Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Data from Three Cohorts of Phase 1b/2 KEYNOTE-365 Study to Be
Presented Today at the 2019 Genitourinary Cancers Symposium (ASCO GU)

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/MRK?src=hash” target=”_blank”gt;#MRKlt;/agt;–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced the presentation of interim data from the Phase 1b/2
KEYNOTE-365 umbrella trial investigating KEYTRUDA, Merck’s anti-PD-1
therapy, in combination with various agents for the treatment of
patients with metastatic castration-resistant prostate cancer (mCRPC).
These early findings show anti-tumor activity across three cohorts of
the study, which investigated KEYTRUDA in combination with LYNPARZA
(Cohort A, Abstract #145); docetaxel and prednisone (Cohort B, Abstract
#170); and enzalutamide (Cohort C, Abstract #171) – with a safety
profile consistent with each therapy alone. These results are being
presented today at the 2019 Genitourinary Cancers Symposium (ASCO GU) in
San Francisco. Based on the findings, Merck is initiating three new
pivotal Phase 3 trials with KEYTRUDA in combination with LYNPARZA
(KEYLYNK-010, NCT03834519), docetaxel and prednisone (KEYNOTE-921,
NCT03834506) and enzalutamide (KEYNOTE-641, NCT03834493).

At the core of our research program is a commitment to investigate the
potential of KEYTRUDA – both as combination and monotherapy – to serve
as a foundational treatment, especially for cancers where additional
therapies are needed,” said Dr. Roy Baynes, senior vice president, head
of global clinical development, and chief medical officer, Merck
Research Laboratories. “These promising data presented at ASCO GU
coupled with the significant unmet medical need in patients with
metastatic castration-resistant prostate cancer, propelled us to
initiate three new Phase 3 trials to further evaluate these KEYTRUDA
combination regimens.”

Merck’s existing clinical development program in metastatic prostate
cancer includes studies evaluating KEYTRUDA and LYNPARZA as monotherapy
and in combination with other anti-cancer therapies with various
mechanisms of action. Ongoing trials include the Phase 2 KEYNOTE-199
trial for KEYTRUDA monotherapy and, in collaboration with AstraZeneca,
the Phase 3 trials PROfound evaluating LYNPARZA monotherapy and PROPEL
evaluating LYNPARZA in combination with abiraterone as a first-line
therapy in patients with mCRPC. With the initiation of KEYLYNK-010,
KEYNOTE-921 and KEYNOTE-641, Merck now has the largest clinical program
with an anti-PD-1 therapy in prostate cancer and the only program to
evaluate overall survival (OS) as a co-primary endpoint across three
Phase 3 trials.

Data from KEYNOTE-365 Presented at ASCO GU

KEYNOTE-365 (NCT02861573) is an ongoing global, open-label,
non-randomized, multi-cohort, multi-center, Phase 1b/2 study evaluating
the safety and efficacy of KEYTRUDA (200 mg fixed dose every three
weeks) in combination with LYNPARZA (Cohort A), docetaxel and prednisone
(Cohort B) and enzalutamide (Cohort C) for the treatment of patients
with mCRPC. The primary endpoints are safety, prostatic specific antigen
(PSA) response rate (measured by confirmed decrease in PSA of 50% or
greater) and overall response rate (ORR) as determined by Response
Evaluation Criteria in Solid Tumors (RECIST) v1.1; secondary endpoints
include disease control rate (DCR), radiographic progression-free
survival (rPFS) and OS. The study is designed to enroll 400 patients
across four cohorts, with outcome measures assessed individually for
each cohort. Data at ASCO GU include interim efficacy and safety
findings from three of the study cohorts (A, B and C).

Data and Safety from Cohort A (Abstract #145)

Cohort A is reported on 41 enrolled patients previously treated with
docetaxel, and up to one other chemotherapy and up to two
second-generation anti-hormone therapies. Patients in Cohort A received
KEYTRUDA in combination with LYNPARZA (400 mg capsules orally twice
daily).

The efficacy analysis from Cohort A presented at ASCO GU showed a PSA
response rate of 12 percent in the total cohort population (n=5/41), 14
percent among patients with measurable disease (n=4/28) and 8 percent
(n=1/13) among patients with non-measurable disease. The median time to
PSA progression was 15.3 (95% CI, 9.3-27.1) and 18.1 (95% CI, 9.3-21.0)
weeks for patients with measurable and non-measurable disease,
respectively. Among patients with measurable disease, the ORR was 7
percent (95% CI, 1-23), with a partial response rate of 7 percent
(n=2/28). The disease control rate (of 6 months or more) was 29 percent
(95% CI, 16-45) in the total cohort population, 32 percent (95% CI,
16-52) among patients with measurable disease and 23 percent (95% CI,
5-54) among patients with non-measurable disease. In an analysis of rPFS
and OS endpoints, the median rPFS was 4.7 months (95% CI, 4.0-7.7) and
the six-month rPFS rate was 48 percent; the median OS was 13.5 months at
the time of analysis (95% CI, 7.7-NR) and the six-month OS rate was 73
percent.

Analysis of the safety data showed that 49 percent of patients had a
grade 3 or 4 treatment-related adverse event (TRAE), the most common
(occurring in ≥10% of patients) of which was anemia (27%).
Immune-mediated adverse events observed in this cohort were grade 1 or 2
and occurred in 49 percent of patients; the most commonly reported
immune-mediated adverse event was hypothyroidism (5%). One patient died
of a TRAE of unknown cause.

Data and Safety from Cohort B (Abstract #170)

Cohort B is reported on 72 enrolled patients previously treated with
either abiraterone acetate or enzalutamide and who had not received
chemotherapy. Patients in Cohort B received KEYTRUDA in combination with
docetaxel (75 mg) plus prednisone (5 mg) orally twice daily.

The efficacy analysis from Cohort B presented at ASCO GU showed a PSA
response rate of 31 percent in the total cohort population (n=22/72), 22
percent among patients with measurable disease (n=8/36) and 39 percent
among patients with non-measurable disease (n=14/36). The median time to
PSA progression was 24.1 (95% CI, 15.1-30) and 30.4 (95% CI, 15.0-36.3)
weeks for patients with measurable and non-measurable disease,
respectively. Among patients with measurable disease, the ORR was 14
percent (95% CI, 5-29), with a partial response rate of 14 percent
(n=5/36). The disease control rate (of 6 months or more) was 57 percent
(95% CI, 45-69) in the total cohort population, 50 percent (95% CI,
33-67) among patients with measurable disease and 64 percent (95% CI,
46-79) among patients with non-measurable disease. The median duration
of response was 4.9 months (95% CI, 4.0-8.3+). In an analysis of rPFS
and OS endpoints, the median rPFS was 8.3 months (95% CI, 7.5-10.2) and
the six-month rPFS rate was 79 percent; the median OS had not been
reached at the time of analysis (95% CI, 12.9-NR); the six-month OS rate
was 96 percent.

Analysis of the safety data showed that 36 percent of patients had a
grade 3-5 TRAE, the most common (occurring in ≥10% of patients) of which
was febrile neutropenia (12%). Immune-mediated adverse events occurred
in 33 percent of patients, the most common (occurring in ≥ 10% of
patients) of which were infusion-related reactions (11%) and colitis
(10%); two patients died due to TRAEs (pneumonitis).

Data and Safety from Cohort C (Abstract #171)

Cohort C is reported on 69 enrolled patients previously treated with
abiraterone acetate and who had not received chemotherapy. Patients in
Cohort C received KEYTRUDA in combination with enzalutamide (160 mg per
day orally).

The efficacy analysis from Cohort C presented at ASCO GU showed a PSA
response rate of 26 percent in the total population (n=18/69), 40
percent among patients with measurable disease (n=10/25), and 18 percent
among patients with non-measurable disease (n=8/44). The median time to
PSA progression was 18.4 (95% CI, 15.4-48.3) and 12.4 (95% CI,
12.0-15.1) weeks for patients with measurable and non-measurable
disease, respectively. Among patients with measurable disease, the ORR
was 20 percent (95% CI, 7-41), with a complete response of 8 percent
(n=2/25) and partial response of 12 percent (n=3/25). The disease
control rate (of 6 months or more) was 33 percent (95% CI, 22-46) in the
total population, 32 percent (95% CI 15-53) among patients with
measurable disease and 34 percent (95% CI, 20-50) among patients with
non-measurable disease. The median duration of response was 8.3 months
(range, 0.0+-13.0+) – and at the time of analysis, 75 percent of
patients had responses lasting for six months or longer. In an analysis
of rPFS and OS endpoints, the median rPFS was 6.1 months (95% CI,
4.0-8.1); the six-month rPFS rate was 59 percent; the median OS had not
been reached at the time of analysis (95% CI, 12.2-NR); the six-month OS
rate was 91 percent.

Analysis of the safety data showed that 41 percent of patients had a
grade 3 or 4 TRAE, the most common (occurring in ≥ 10% of patients) of
which was rash (10%). Immune-mediated adverse events occurred in 41
percent of patients, the most common (occurring in ≥ 10% of patients) of
which were severe skin reactions (20%) and hypothyroidism (13%). No
patients died of TRAEs.

About Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Prostate cancer is typically driven by male sex hormones called
androgens, including testosterone. Castration-resistant prostate cancer
(CRPC) is characterized when the cancer continues to grow despite
surgery or treatment to lower the amount of male sex hormones. When CRPC
spreads to other parts of the body, it is referred to as metastatic
castration-resistant prostate cancer or mCRPC. Prostate cancer is the
second most common cancer in men, with an estimated 1.3 million new
cases diagnosed worldwide in 2018. In the United States, an estimated
174,650 men will be diagnosed with prostate cancer in 2019 and one in
nine men will be diagnosed in his lifetime. Approximately 10-20 percent
of men with prostate cancer will develop CRPC within five years; within
two years of a CRPC diagnosis, 33 percent of men will develop mCRPC.

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, 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 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 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 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 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.

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 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 PMBCL, 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 (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 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 a fixed dose 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 a fixed dose 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 a fixed dose 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 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of hypophysitis (including
hypopituitarism and adrenal insufficiency), thyroid function (prior to
and periodically during treatment), and hyperglycemia.

Contacts

Media Contacts:
Pamela Eisele
(267) 305-3558
Ayn
Wisler
(908) 740-5590
Investor Contacts:
Teri Loxam
(908)
740-1986
Peter Dannenbaum
(908) 740-1037

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