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June 6, 2016 7:00 am ET

Findings Support Initiation of Phase 3 Pivotal Study (KEYNOTE-204) Evaluating KEYTRUDA Versus Brentuximab Vedotin in Relapsed or Refractory cHL

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the first-time presentation of findings from
KEYNOTE-087, the phase 2 study investigating the use of KEYTRUDA^® (pembrolizumab),
the company’s anti-PD-1 therapy, as a monotherapy in patients with
relapsed or refractory classical Hodgkin lymphoma (cHL). These data will
be presented today at the 52^nd Annual Meeting of the American
Society of Clinical Oncology (ASCO) in Chicago from 8:00 – 11:30 a.m.
CDT (Location: Hall A) and in a poster discussion from 1:15 – 2:45 p.m.
CDT (Location: E354b) (Abstract #7555).

Results included an analysis of outcome measurements from the study’s
three patient cohorts: patients whose disease progressed following an
autologous stem cell transplantation and subsequent treatment with
brentuximab vedotin, an antibody drug conjugate (Cohort 1); patients who
failed salvage chemotherapy and were ineligible for a transplant and
whose disease progressed following treatment with brentuximab vedotin
(Cohort 2); and patients whose disease progressed after transplant and
who did not receive brentuximab vedotin after transplant (Cohort 3).
Data showed that the overall response rate (ORR) was more than 70
percent across all three cohorts with the highest ORR, at 83 percent,
observed in Cohort 2. Results also included an analysis of patients with
primary refractory disease, defined as failure to achieve complete or
partial response to first-line treatment. In this patient population,
the ORR (by investigator review) was 78 percent. Additionally, 90 to 93
percent of patients experienced a reduction in tumor size across all
three cohorts.

“Recurrence of Hodgkin lymphoma occurs in almost half of patients
following autologous stem cell transplantation, and the prognosis for
patients relapsing or refractory to second-line chemotherapy and
transplant is particularly poor, which means there is a significant need
to identify therapeutic options that provide meaningful clinical
benefit,” said Dr. Craig Moskowitz, clinical director, division of
hematologic oncology, Memorial Sloan Kettering Cancer Center. “These
early data are encouraging, as they demonstrate high response rates – up
to 83 percent – with pembrolizumab in heavily pre-treated patients.”

Data from KEYNOTE-087 supported the recent Breakthrough Therapy
Designation granted to KEYTRUDA (pembrolizumab) by the U.S. Food and
Drug Administration (FDA) for this type of blood cancer. Additionally,
findings from this study support the continued development of KEYTRUDA
in patients with cHL, including a phase 3 registration-enabling study
(KEYNOTE-204) designed to evaluate monotherapy KEYTRUDA versus
brentuximab vedotin in patients with relapsed or refractory cHL.

“Our extensive clinical development program is studying KEYTRUDA in a
broad range of solid and blood cancers – including classical Hodgkin
lymphoma, where there remains a significant unmet need for patients who
do not respond to or relapse following initial treatment,” said Dr.
Roger Dansey, senior vice president and therapeutic area head, oncology
late-stage development, Merck Research Laboratories. “These exciting
data from KEYNOTE-087 reinforce the potential of KEYTRUDA in hematologic
cancers and further invigorate our commitment to improving outcomes
across a variety of blood cancers.”

Results presented at ASCO were based on an analysis of 90 patients
across three study cohorts. These data showed (per investigator review):

• In Cohort 1 (progressed after transplant and subsequent brentuximab
  vedotin treatment; n=30), ORR was 73 percent (95% CI, 54-88) – with
  complete responses in 27 percent (95% CI, 12-46) and partial responses
  in 47 percent (95% CI, 28-66) of patients. Seventeen percent of
  patients had stable disease (95% CI, 6-35) and 10 percent of patients
  had progressive disease (95% CI, 2-27).
• In Cohort 2 (progressed following salvage chemotherapy,
  transplant-ineligible, and progressed following brentuximab vedotin
  treatment; n=30), ORR was 83 percent (95% CI, 65-94) – with complete
  responses in 30 percent (95% CI, 15-49) and partial responses in 53
  percent (95% CI, 34-72) of patients. Seven percent of patients had
  stable disease (95% CI, 1-22) and 7 percent of patients had
  progressive disease (95% CI, 1-22).
• In Cohort 3 (progressed after transplant and not treated with
  brentuximab vedotin after transplant; n=30), ORR was 73 percent (95%
  CI, 54-88) – with complete responses in 30 percent (95% CI, 15-49) and
  partial responses in 43 percent of patients (95% CI, 26-63). Thirteen
  percent of patients had stable disease (95% CI, 4-31) and 13 percent
  of patients had progressive disease (95% CI, 4-31).

In patients with primary refractory disease (n=37), ORR was 78 percent
(95% CI, 62-90) – with complete responses in 35 percent (95% CI, 20-53)
and partial responses in 43 percent (95% CI, 27-61) of patients. Eleven
percent of patients had stable disease (95% CI, 3-25) and 8 percent of
patients had progressive disease (95% CI, 2-22).

The safety profile of KEYTRUDA (pembrolizumab) was consistent with that
observed in previously reported studies. Grade 3-4 treatment-related
adverse events were observed in 4 percent of patients and included
neutropenia (n=1), increased amylase (n=1), cytokine release syndrome
(n=1), herpes zoster (n=1), increased lipase (n=1), lichenoid dermatosis
(n=1), colitis (n=1), and diarrhea (n=1). Two patients discontinued due
to treatment-related adverse events (Grade 2 infusion-related reaction
and Grade 2 pneumonitis; both Cohort 2). The immune-mediated adverse
events (any grade) were rash (n=4, all Grade 1), pneumonitis (n=2, both
Grade 2), and colitis (n=1, Grade 3). There were no treatment-related
deaths.

The KEYTRUDA clinical development program includes more than 30 tumor
types in more than 270 clinical trials, including more than 100 trials
that combine KEYTRUDA with other cancer treatments. For hematologic
malignancies specifically, Merck is conducting a broad immuno-oncology
clinical development program. To date, the program is assessing the role
of monotherapy and combination regimens with KEYTRUDA across a variety
of hematologic malignancies including leukemia, lymphomas, and myeloma,
and includes five registration-enabling studies.

About KEYNOTE-087

KEYNOTE-087 is a multicenter, open-label, multi-cohort,
activity-estimating phase 2 trial evaluating KEYTRUDA (200 mg fixed dose
every three weeks) monotherapy in patients with relapsed or refractory
cHL across three cohorts. The primary endpoints include overall safety,
tolerability, and ORR (per central review); secondary endpoints include
ORR (per investigator review), progression-free survival (PFS), and
overall survival (OS). The patient cohorts are intended to assess the
outcome measures in patients whose disease progressed following an
autologous stem cell transplantation and subsequent treatment with
brentuximab vedotin, an antibody drug conjugate (Cohort 1); patients who
failed salvage chemotherapy and were ineligible for a transplant and
whose disease progressed following treatment with brentuximab vedotin
(Cohort 2); and patients whose disease progressed after transplant and
who did not receive brentuximab vedotin after transplant (Cohort 3).

About KEYTRUDA

^®

(pembrolizumab) Injection
100 mg

KEYTRUDA is a humanized monoclonal antibody that works by increasing the
ability of the body’s immune system to help detect and fight tumor
cells. KEYTRUDA 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.

KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic melanoma.

KEYTRUDA is also indicated for the treatment of patients with metastatic
non-small cell lung cancer (NSCLC) whose tumors express PD-L1 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. This
indication is approved under accelerated approval based on tumor
response rate and durability of response. An improvement in survival or
disease-related symptoms has not yet been established. Continued
approval for this indication may be contingent upon verification and
description of clinical benefit in the confirmatory trials.

KEYTRUDA is administered at a dose of 2 mg/kg as an intravenous infusion
over 30 minutes every three weeks for the approved indications.

Selected Important Safety Information for KEYTRUDA

^®

 (pembrolizumab)

Immune-mediated pneumonitis, including fatal cases, occurred in patients
receiving KEYTRUDA. Pneumonitis occurred in 32 (2.0%) of 1567 patients
with melanoma, including Grade 1 (0.8%), 2 (0.8%), and 3 (0.4%)
pneumonitis. Pneumonitis occurred in 19 (3.5%) of 550 patients with
NSCLC, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%)
pneumonitis and more frequently in patients with a history of
asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic
radiation (6.0%). 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 occurred in 31 (2%) of 1567 patients with
melanoma, including Grade 2 (0.5%), 3 (1.1%), and 4 (0.1%) colitis.
Immune-mediated colitis occurred in 4 (0.7%) of 550 patients with NSCLC,
including Grade 2 (0.2%) or 3 (0.4%) colitis. Monitor patients for signs
and symptoms of colitis. Administer corticosteroids for Grade 2 or
greater colitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2 or 3;
permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-mediated hepatitis occurred in patients receiving KEYTRUDA.
Hepatitis occurred in 16 (1%) of 1567 patients with melanoma, including
Grade 2 (0.1%), 3 (0.7%), 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.

Hypophysitis occurred in 13 (0.8%) of 1567 patients with melanoma,
including Grade 2 (0.3%), 3 (0.3%), and 4 (0.1%) hypophysitis.
Hypophysitis occurred in 1 (0.2 %) of 550 patients with NSCLC, which was
Grade 3 in severity. 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.

Hyperthyroidism occurred in 51 (3.3%) of 1567 patients with melanoma,
including Grade 2 (0.6%) and 3 (0.1%) hyperthyroidism. Hypothyroidism
occurred in 127 (8.1%) of 1567 patients with melanoma, including Grade 3
(0.1%) hypothyroidism. Hyperthyroidism occurred in 10 (1.8%) of 550
patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%)
hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients
with NSCLC, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. Thyroid
disorders can occur at any time during treatment. Monitor patients for
changes in thyroid function (at the start of treatment, periodically
during treatment, and as indicated based on clinical evaluation) and for
clinical signs and symptoms of thyroid disorders. Administer replacement
hormones for hypothyroidism and manage hyperthyroidism with thionamides
and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for
Grade 3 or 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3
(0.1%) of 2117 patients. Monitor patients for hyperglycemia or other
signs and symptoms of diabetes. Administer insulin for type 1 diabetes,
and withhold KEYTRUDA and administer anti-hyperglycemics in patients
with severe hyperglycemia.

Immune-mediated nephritis occurred in patients receiving KEYTRUDA.
Nephritis occurred in 7 (0.4%) of 1567 patients with melanoma including,
Grade 2 (0.2%), 3 (0.2%), and 4 (0.1%) nephritis. Monitor patients for
changes in renal function. Administer corticosteroids for Grade 2 or
greater nephritis. Withhold KEYTRUDA (pembrolizumab) for Grade 2;
permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur.
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 1567 patients
with melanoma: arthritis (1.6%), exfoliative dermatitis, bullous
pemphigoid, uveitis, myositis, Guillain-Barré syndrome, myasthenia
gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures
arising in a patient with inflammatory foci in brain parenchyma. The
following clinically significant, immune-mediated adverse reactions
occurred in less than 1% of 550 patients with NSCLC: rash, vasculitis,
hemolytic anemia, serum sickness, and myasthenia gravis.

Severe and life-threatening infusion-related reactions have been
reported in 3 (0.1%) of 2117 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.

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 Trial 6, 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 occurred in 21% of patients; the most common (≥1%) was diarrhea
(2.5%). The most common adverse reactions with KEYTRUDA (pembrolizumab)
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 Trial 2, KEYTRUDA was discontinued due to adverse reactions in 12% of
357 patients with advanced melanoma; the most common (≥1%) were general
physical health deterioration (1%), asthenia (1%), dyspnea (1%),
pneumonitis (1%), and generalized edema (1%). Adverse reactions leading
to interruption of KEYTRUDA occurred in 14% of patients; the most common
(≥1%) were dyspnea (1%), diarrhea (1%), and maculo-papular rash (1%).
The most common adverse reactions with KEYTRUDA vs chemotherapy were
fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%),
constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs
20%), and decreased appetite (20% with KEYTRUDA). Corresponding
incidence rates are listed for chemotherapy only for those adverse
reactions that occurred at the same or lower rate than with KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 14% of 550
patients with NSCLC. Serious adverse reactions occurred in 38% of
patients. The most frequent serious adverse reactions reported at least
2% of patients were pleural effusion, pneumonia, dyspnea, pulmonary
embolism, and pneumonitis. The most common adverse reactions (reported
in at least 20% of patients) were fatigue (44%), cough (29%), decreased
appetite (25%), and dyspnea (23%).

No formal pharmacokinetic drug interaction studies have been conducted
with KEYTRUDA.

It is not known whether KEYTRUDA is excreted in human milk. Because many
drugs are excreted in human milk, instruct women to discontinue nursing
during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in
pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology
medicines to help people with cancer worldwide. At Merck Oncology,
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 270 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 125 years, Merck has been a global health care leader working to
help the world be well. Merck is known as MSD outside the United States
and Canada. Through our prescription medicines, vaccines, biologic
therapies, and animal health products, we work with customers and
operate in more than 140 countries to deliver innovative health
solutions. We also demonstrate our commitment to increasing access to
health care through far-reaching policies, programs and partnerships.
For more information, visit www.merck.com
and connect with us on Twitter,
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and 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 2015 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

.

Merck
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