Merck Announces Findings from Phase 3 Study of KEYTRUDA ® (pembrolizumab),
Compared to Standard of Care, in Patients with Previously Treated Recurrent or Metastatic Head and Neck Squamous Cell
Carcinoma
First Presentation of KEYNOTE-040 Results at ESMO 2017 Congress
Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced results of the phase 3 KEYNOTE-040 trial
investigating KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, compared to standard treatment (methotrexate,
docetaxel or cetuximab) in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease
progression on or after platinum-containing chemotherapy. As previously disclosed, the study did not meet its pre-specified primary
endpoint of overall survival (OS). The findings include updated survival data showing a 19 percent reduction in the risk of death
over standard treatment in the intent-to-treat population (HR, 0.81 [95% CI, 0.66-0.99]; one sided p = 0.0204), with pre-specified
p-value required for statistical significance of 0.0175, and a median OS of 8.4 months with KEYTRUDA (95% CI, 6.5-9.4) compared to
7.1 months with standard treatment (95% CI, 5.9-8.1). Complete results will be presented for the first time at the European Society
for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain, in an oral presentation today from 3:00 – 3:12 p.m. CEST
(Location: Granada Auditorium) (Abstract #LBA45_PR).
“These data, including progression-free survival and overall response rate, show the activity and efficacy of pembrolizumab in
this disease, and are consistent with prior studies of pembrolizumab in recurrent head and neck squamous cell carcinoma,” said Ezra
Cohen, M.D., associate director for translational science, Moores Cancer Center and co-director of the San Diego Center for
Precision Immunotherapy, University of California, San Diego. “KEYNOTE-40 strengthens the rationale for further studies, and
expansion into earlier lines of disease.”
With more than 20 trials, Merck currently has the largest immuno-oncology clinical development program in head and neck cancer
and is advancing multiple registration-enabling studies investigating KEYTRUDA (pembrolizumab) as monotherapy and in combination
with other cancer treatments – including KEYNOTE-048 and KEYNOTE-412.
“Although the primary efficacy analysis did not show a statistically significant improvement in overall survival, these data add
to the evolving science for KEYTRUDA in head and neck cancer,” said Dr. Jon Cheng, associate vice president, Merck Research
Laboratories.
Data in Second-Line Treatment Setting, KEYNOTE-040 (Abstract #LBA45_PR)
KEYNOTE-040 is a randomized, multi-center, phase 3 study investigating KEYTRUDA as a monotherapy (n=247) versus standard
treatment (methotrexate, docetaxel or cetuximab) (n=248) in patients with recurrent or metastatic HNSCC (additional details on the
trial design are provided below).
Data presented at ESMO are based on findings in the intent-to-treat population (n=495) and include analysis of efficacy
endpoints based on PD-L1 expression using two measurements: PD-L1 CPS ≥1 (n=387) and PD-L1 TPS ≥50% (n=129). More than a third of
patients in the intent-to-treat population went on to receive subsequent therapy, including 11 of 84 patients in the KEYTRUDA arm
and 31 of 100 patients in the standard treatment arm who received subsequent treatment with an immune checkpoint inhibitor. Other
subsequent treatments included chemotherapy, EGFR inhibitor, kinase inhibitor, other immunotherapy, and other treatments.
Data show that in the intent-to-treat population, the median OS was 8.4 months with KEYTRUDA (95% CI, 6.5-9.4) compared to 7.1
months with standard treatment (95% CI, 5.9-8.1) (HR, 0.81 [95% CI, 0.66-0.99]; one sided p = 0.0204); the 12-month OS rate was
37.3 percent with KEYTRUDA compared to 27.2 percent with standard treatment. Further analysis of the primary endpoint based on
PD-L1 expression showed:
- In patients with PD-L1 CPS ≥1, the median OS was 8.7 months with KEYTRUDA (95% CI, 6.9-11.4) and 7.1
months with standard treatment (95% CI, 5.7-8.6) (HR, 0.75 [95% CI, 0.59-0.95]; p = 0.0078); the 12-month OS rate was 40.1
percent with KEYTRUDA compared to 26.7 percent with standard treatment.
- In patients with PD-L1 TPS ≥50%, the median OS was 11.6 months with KEYTRUDA (95% CI, 8.3-19.5) and
7.9 months with standard treatment (95% CI, 4.8-9.3) (HR, 0.54 [95% CI, 0.35-0.82]; p = 0.0017); the 12-month OS rate was 46.6
percent with KEYTRUDA compared to 25.8 percent with standard treatment.
The overall response rate (ORR) in the intent-to-treat population was 14.6 percent in the KEYTRUDA (pembrolizumab) arm compared
to 10.1 percent in the standard treatment arm (p = 0.0610). In patients with PD-L1 CPS ≥1, the ORR was 17.3 percent with KEYTRUDA
compared to 9.9 percent with standard treatment (p = 0.0171). In patients with PD-L1 TPS ≥50%, the ORR was 26.6 percent with
KEYTRUDA compared to 9.2 percent with standard treatment (p = 0.0009).
The median progression-free survival (PFS) was 2.1 months in the intent-to-treat population with KEYTRUDA (95% CI, 2.1-2.3) and
2.3 months with standard treatment (95% CI, 2.1-2.8) (HR, 0.95 [95% CI, 0.79-1.16]; p = 0.3037). In patients with PD-L1 CPS ≥1, the
median PFS was 2.2 months with KEYTRUDA (95% CI, 2.1-3.0) and 2.3 months with standard treatment (95% CI, 2.1-3.3) (HR, 0.89 [95%
CI, 0.72-1.11]; p = 0.1526). In patients with PD-L1 TPS ≥50%, the median PFS was 3.5 months with KEYTRUDA (95% CI, 2.1-6.3) and 2.2
months with standard treatment (95% CI, 2.0-2.5) (HR, 0.58 [95% CI, 0.39-0.87]; p = 0.0034).
The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Treatment-related adverse
events (TRAEs) of any grade occurred in 155 patients (63.0%) in the KEYTRUDA arm and 196 patients (83.8%) in the standard treatment
arm. Across any arm, TRAEs with incidence of 10 percent or more included hypothyroidism, fatigue, diarrhea, rash, asthenia, anemia,
nausea, mucosal inflammation, stomatitis, decreased neutrophil count and alopecia. Immune-mediated adverse events, any grade,
occurring in the KEYTRUDA arm were hypothyroidism, pneumonitis, infusion reactions, severe skin reactions, hyperthyroidism,
colitis, Guillain-Barre syndrome and hepatitis. Discontinuation due to TRAEs occurred in 15 patients (6.1%) in the KEYTRUDA arm and
12 patients (5.1%) in the standard treatment arm. Deaths due to treatment-related adverse events occurred in four patients (1.6%)
in the KEYTRUDA arm and two patients (0.9%) in the standard treatment arm.
About KEYNOTE-040
KEYNOTE-040 is a randomized, multi-center, pivotal phase 3 study investigating KEYTRUDA as a monotherapy versus standard
treatment (methotrexate, docetaxel or cetuximab) for the treatment of recurrent or metastatic HNSCC. The primary endpoint is OS;
secondary endpoints include PFS and ORR. The study, which opened in November 2014, enrolled 495 patients to receive KEYTRUDA (200
mg fixed dose every three weeks) or investigator-choice chemotherapy (methotrexate [40 mg/m2 on Days 1, 8, and 15 of
each 3-week cycle], docetaxel [75 mg/m2 on Day 1 of each 3-week cycle], or cetuximab [400 mg/m2 loading dose
on Day 1 and 250 mg/m2 IV on Days 8 and 15 of Cycle 1], followed by cetuximab [250 mg/m2 on Days 1, 8, and 15
of each subsequent 3-week cycle]). Patients enrolled in the study had been previously treated with one to two platinum-containing
systemic regimens.
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, 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 (pembrolizumab) 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 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 (pembrolizumab) 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 (pembrolizumab) 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 (0.5%)
hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, 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 (pembrolizumab) 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. 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 (pembrolizumab) 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 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 (pembrolizumab) 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 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-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic
urothelial carcinoma. The most common adverse reactions (in≥20% of patients) were fatigue (38%), musculoskeletal pain (24%),
decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%). Eighteen patients (5%) died from causes other than
disease progression. Five patients (1.4%) who were treated with KEYTRUDA experienced sepsis which led to death, and 3 patients
(0.8%) experienced pneumonia which led to death. Adverse reactions leading to interruption of KEYTRUDA (pembrolizumab) occurred in
22% of patients; the most common (≥1%) were liver enzyme increase, diarrhea, urinary tract infection, acute kidney injury, fatigue,
joint pain, and pneumonia. Serious adverse reactions occurred in 42% of patients, the most frequent (≥2%) of which were urinary
tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis.
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.
There is limited experience in pediatric patients. Efficacy for pediatric patients was extrapolated from the results in the
adult cHL population. In a study of 40 pediatric patients with advanced melanoma, PD-L1–positive advanced, relapsed, or refractory
solid tumors or lymphoma, patients were treated with KEYTRUDA for a median of 43 days (range 1-414 days), with 24 patients (60%)
receiving treatment for 42 days or more. The safety profile in pediatric patients was similar to that seen in adults treated with
KEYTRUDA. Toxicities that occurred at a higher rate (≥15% difference) in these patients when compared to adults under 65 years of
age were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).
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.
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 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
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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 .
Merck
Media:
Pamela Eisele, 267-305-3558
Elizabeth Sell, 267-305-3877
or
Investors:
Teri Loxam, 908-740-1986
Amy Klug, 908-740-1898
View source version on businesswire.com: http://www.businesswire.com/news/home/20170911005592/en/