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November 3, 2015 6:58 am ET

• Phase I first-in-human study to evaluate GSK’s OX40 agonist GSK3174998 as monotherapy and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA^® (pembrolizumab)

GSK and Merck, known as MSD outside the US and Canada, today announced
the initiation of a phase I clinical trial designed to evaluate GSK’s
investigational immunotherapy GSK3174998 as monotherapy and in
combination with Merck’s anti-PD-1 therapy, KEYTRUDA^® (pembrolizumab)
in patients with locally advanced, recurrent or metastatic solid
tumour(s) that have progressed after standard treatment.

GSK3174998 is a humanised IgG1 anti-OX40 monoclonal antibody that was
identified through a collaboration with MD Anderson Cancer Center. OX40
is a tumour necrosis factor receptor expressed on the surface of
activated CD4+ and CD8+ T cells. OX40 agonism results in stimulation of
both immune effector and memory functions, while also attenuating the
immunosuppressive regulatory T cells that are sometimes found in
tumours. GSK3174998 is one of a number of early stage assets in GSK’s
oncology pipeline focused on fighting the fundamental drivers of cancer.
KEYTRUDA is a humanised monoclonal antibody that works by increasing the
ability of the body’s immune system to help detect and fight tumour
cells. KEYTRUDA blocks the interaction between PD-1 and its ligands,
PD-L1 and PD-L2, and may affect both tumour cells and healthy cells.

Axel Hoos, Vice President Oncology R&D at GSK, said: “There have been
meaningful advances in survival across several cancers recently, mostly
based on single agent checkpoint modulatory drugs. The combination study
of KEYTRUDA with GSK’s OX40 agonist will seek to build on that progress
with the aim of contributing further improvements for patients. We think
combining these two agents that use different aspects of the immune
system may be an important step toward achieving this goal.”

“The initiation of this phase I trial with GSK is an important step in
identifying synergistic treatment combinations that can potentially
enhance the activity we are seeing with KEYTRUDA as a monotherapy,” said
Dr. Eric Rubin, vice president and therapeutic area head, oncology early
stage development, Merck Research Laboratories. “We are looking forward
to this trial progressing and to sharing the findings on the potential
of the combination of KEYTRUDA and GSK’s GSK3174998 in bringing forward
improved outcomes for patients with advanced cancer.”

More information on the clinical trial can be found by searching for
NCT02528357 on www.clinicaltrials.gov

About KEYTRUDA^® (pembrolizumab)

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 in the United States at a dose of 2 mg/kg
administered as an intravenous infusion over 30 minutes every three
weeks 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. KEYTRUDA is
also indicated at the same dosing for the treatment of patients with
unresectable or metastatic melanoma and disease progression following
ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. These
indications are 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 these indications may be contingent upon verification and
description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

Pneumonitis, including fatal cases, occurred in patients receiving
KEYTRUDA. Pneumonitis occurred in 12 (2.9%) of 411 melanoma patients,
including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients,
respectively, receiving KEYTRUDA. 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 in patients, receiving KEYTRUDA. 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.

Colitis (including microscopic colitis) occurred in 4 (1%) of 411
patients with melanoma, including Grade 2 or 3 cases in 1 (0.2%) and 2
(0.5%) patients, respectively, receiving KEYTRUDA. Colitis occurred in 4
(0.7 %) of 550 patients with NSCLC, including Grade 2 (0.2%) or 3 (0.4%)
colitis in patients receiving KEYTRUDA. 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.

Hepatitis occurred in patients receiving KEYTRUDA. Hepatitis (including
autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients with
melanoma, including a Grade 4 case in 1 (0.2%) patient, receiving
KEYTRUDA. 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 2 (0.5%) of 411 patients with melanoma,
including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each)
patient, receiving KEYTRUDA. 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 indicated. Withhold KEYTRUDA for Grade 2 and withhold or
discontinue for Grade 3 or Grade 4 hypophysitis.

Hyperthyroidism occurred in 5 (1.2%) of 411 patients with melanoma,
including Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients,
respectively, receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%)
of 411 patients with melanoma, including a Grade 3 case in 1 (0.2%)
patient, receiving KEYTRUDA. Hyperthyroidism occurred in 10 (1.8%) of
550 patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%).
Hypothyroidism occurred in 38 (6.9%) of 550 patients with NSCLC,
including Grade 2 (5.5%) or 3 (0.2%). 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 Grade 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred
in patients receiving KEYTRUDA. 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.

Nephritis occurred in patients receiving KEYTRUDA. Nephritis occurred in
3 (0.7%) patients with melanoma, consisting of one case of Grade 2
autoimmune nephritis (0.2%) and two cases of interstitial nephritis with
renal failure (0.5%), one Grade 3 and one Grade 4. 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.

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 of the adverse reaction to Grade 1 or
less, initiate corticosteroid taper and continue to taper over at least
1 month. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or
less following steroid taper. Permanently discontinue KEYTRUDA for any
severe or Grade 3 immune-mediated adverse reaction that recurs and for
any life-threatening immune-mediated adverse reaction.

Across clinical studies with KEYTRUDA, the following clinically
significant, immune-mediated adverse reactions have occurred: bullous
pemphigoid and Guillain-Barré syndrome. The following clinically
significant, immune-mediated adverse reactions occurred in less than 1%
of patients with melanoma treated with KEYTRUDA: exfoliative dermatitis,
uveitis, arthritis, myositis, 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
treated with KEYTRUDA: rash, vasculitis, hemolytic anemia, serum
sickness, and myasthenia gravis.

Infusion-related reactions, including severe and life-threatening
reactions, have occurred in patients receiving KEYTRUDA. Monitor
patients for signs and symptoms of infusion related reactions including
rigors, chills, wheezing, pruritus, flushing, rash, hypotension,
hypoxemia, and fever. For severe or life-threatening 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.

Among the 411 patients with metastatic melanoma, KEYTRUDA was
discontinued for adverse reactions in 9% of 411 patients. Adverse
reactions, reported in at least two patients, that led to
discontinuation of KEYTRUDA were: pneumonitis, renal failure, and pain.
Serious adverse reactions occurred in 36% of patients. The most frequent
serious adverse reactions, reported in 2% or more of patients, were
renal failure, dyspnea, pneumonia, and cellulitis. The most common
adverse reactions (reported in at least 20% of patients) were fatigue
(47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), decreased
appetite (26%), constipation (21%), arthralgia (20%), and diarrhea (20%).

Among the 550 patients with metastatic NSCLC, KEYTRUDA was discontinued
due to adverse reactions in 14% of patients. Serious adverse reactions
occurred in 38% of patients. The most frequent serious adverse reactions
reported in 2% or more 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%),
decreased appetite (25%), dyspnea (23%), and cough (29%).

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.

Please see Prescribing Information for KEYTRUDA (pembrolizumab)
at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf
and the Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf

GSK – one of the world’s leading research-based pharmaceutical
and healthcare companies – is committed to improving the quality of
human life by enabling people to do more, feel better and live longer.
For further information please visit www.gsk.com.

Merck’s 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. For more information about our oncology clinical trials,
visit www.merck.com/clinicaltrials.

About Merck

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