Merck’s KEYTRUDA® (pembrolizumab) Approved in China for First-Line Treatment of
Metastatic Nonsquamous Non-Small Cell Lung Cancer (NSCLC) in Combination with Chemotherapy
KEYTRUDA is First Anti-PD-1 Therapy to be Approved in Multiple Tumor Types in China
Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that KEYTRUDA, Merck’s anti-PD-1 therapy,
has been approved by the National Medical Products Administration (NMPA) in combination with pemetrexed and platinum chemotherapy
for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK
genomic tumor aberrations. This new indication was granted conditional approval based on overall survival (OS) and progression-free
survival (PFS) data from the pivotal Phase 3 KEYNOTE-189 trial in patients regardless of PD-L1 tumor expression status. Continued
approval may be contingent upon verification and description of clinical benefit in Chinese patients in a confirmatory trial. With
this approval, KEYTRUDA is the first anti-PD-1 therapy approved for more than one tumor type in China, following its initial
approval in July 2018 for advanced melanoma, and the first anti-PD-1 therapy approved in the first-line treatment setting for
metastatic nonsquamous NSCLC.
“Lung cancer is a deadly disease and the leading cause of cancer deaths in China, claiming the lives of more than 626,000 people
in our country each year,” said Prof. Yi-Long Wu, honorary director of the Guangdong Lung Cancer Research Institute, and tenured
director of Guangdong Provincial People’s Hospital. “The approval of KEYTRUDA in combination with standard chemotherapy for the
first-line treatment of metastatic nonsquamous non-small cell lung cancer is an important milestone in the treatment of advanced
lung cancer in China.”
In KEYNOTE-189, KEYTRUDA in combination with pemetrexed and platinum chemotherapy resulted in a statistically significant and
clinically meaningful improvement in OS (HR=0.49 [95% CI, 0.38-0.64]; p<0.00001), reducing the risk of death by half compared to
chemotherapy alone. The study also showed a significant improvement in PFS compared to chemotherapy alone (HR=0.52 [95% CI,
0.43-0.64]; p<0.00001).
“This approval represents a key advance in a country with a high incidence of lung cancer, and where significant progress for
the first-line treatment of this devastating disease has been very limited over a number of years,” said Dr. Roy Baynes, senior
vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “This also means that,
based on the results of KEYNOTE-189, KEYTRUDA in combination with chemotherapy has now been approved in the U.S., Europe, Japan and
China, among other countries, for the first-line treatment of appropriate patients with metastatic nonsquamous non-small cell lung
cancer.”
“We are committed to developing innovative therapies and introducing them as quickly as possible to physicians and patients in
China,” said Joseph Romanelli, president of MSD in China. “Patients with metastatic nonsquamous non-small cell lung cancer in China
now have a new option for the first-line treatment of their disease, and we will continue to collaborate with the Chinese
government, healthcare organizations and our business partners to improve patient access to KEYTRUDA in 2019.”
About Lung Cancer in China
Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of
cancer death in China and worldwide. Each year, more than 782,000 new cases of lung cancer are diagnosed in China and more than
626,000 deaths result from the disease. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung
cancer (NSCLC) is the most common type of lung cancer, accounting for about 85 percent of all cases. There are several subtypes of
NSCLC, including adenocarcinoma (accounting for 40% of lung cancers), squamous cell carcinoma (25 to 30%) and large cell carcinoma
(10 to 15%).
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 in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma. The recommended dose of KEYTRUDA
in patients with unresectable or metastatic melanoma is 200 mg administered as an intravenous infusion over 30 minutes every three
weeks until disease progression or unacceptable toxicity.
KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete
resection. The recommended dose of KEYTRUDA for the adjuvant treatment of adult patients with melanoma is 200 mg administered as an
intravenous infusion over 30 minutes every three weeks until disease recurrence, unacceptable toxicity, or for up to 12 months in
patients without disease recurrence.
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 (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 (0.8%) 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. For hypophysitis, administer corticosteroids and hormone
replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or 4 hypophysitis.
Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate.
Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA
and administer antihyperglycemics in patients with severe hyperglycemia.
Immune-Mediated Nephritis and Renal Dysfunction
KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including
Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in
combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids
for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.
Immune-Mediated Skin Reactions
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 and administer corticosteroids. For signs or
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.
Other Immune-Mediated Adverse Reactions
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving
KEYTRUDA and may also occur after discontinuation of treatment. 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, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including cHL,
and postmarketing use.
Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of
treatment vs the risk of possible organ rejection in these patients.
Infusion-Related Reactions
KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have
been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4
reactions, stop infusion and permanently discontinue KEYTRUDA.
Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with
KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease
(GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1
fatal case). 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. Follow patients closely for early evidence of transplant-related
complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome,
hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.
In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with
KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider
the benefit of KEYTRUDA vs the risk of GVHD in these patients.
Increased Mortality in Patients With Multiple Myeloma
In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in
increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended
outside of controlled trials.
Embryofetal Toxicity
Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this
potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use
effective contraception during treatment and for 4 months after the last dose.
Adverse Reactions
In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse
reactions leading to permanent 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%). The most common adverse reactions (≥20%) with KEYTRUDA were
fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).
In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (≥1%)
were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving
KEYTRUDA. The most common adverse reaction ≥20% with KEYTRUDA was diarrhea (28%).
In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC,
KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent
discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (≥20%) with
KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting
(24%), cough (21%), dyspnea (21%), and pyrexia (20%).
In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or nab-paclitaxel in metastatic squamous
NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions
reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in
KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and
peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm
in KEYNOTE-407.
In KEYNOTE-010, 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%). The most common adverse
reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).
In KEYNOTE-012, 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 (≥20%) 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 who received KEYTRUDA as a monotherapy, with the exception of increased incidences of
facial edema and new or worsening hypothyroidism.
In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions
occurred in 16% of patients; those ≥1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients
died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most
common adverse reactions (≥20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and
rash (20%).
In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions
occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion
(2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (≥20%)
were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea
(21%).
In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic
urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those ≥2% were urinary tract infection, hematuria,
acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (≥20%) were fatigue (38%), musculoskeletal pain
(24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).
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%).
Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those ≥2% were urinary tract infection, pneumonia, anemia,
and pneumonitis. The most common adverse reactions (≥20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal
pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).
Adverse reactions occurring in patients with gastric cancer were similar to those occurring in patients with melanoma or NSCLC
who received KEYTRUDA as a monotherapy.
In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with recurrent or metastatic cervical
cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula,
hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (≥20%) were fatigue
(43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).
Adverse reactions occurring in patients with HCC were generally similar to those in patients with melanoma or NSCLC who received
KEYTRUDA as a monotherapy, with the exception of increased incidences of ascites (8% Grades 3-4) and immune-mediated hepatitis
(2.9%). Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and
hyperbilirubinemia (10%).
Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse reactions occurring in patients with MCC were generally
similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. Laboratory abnormalities
(Grades 3-4) that occurred at a higher incidence were elevated AST (11%) and hyperglycemia (19%).
Lactation
Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment
and for 4 months after the final dose.
Pediatric Use
There is limited experience in pediatric patients. In a trial, 40 pediatric patients (16 children aged 2 years to younger than
12 years and 24 adolescents aged 12 years to 18 years) with various cancers, including unapproved usages, were administered
KEYTRUDA 2 mg/kg every 3 weeks. Patients received KEYTRUDA for a median of 3 doses (range 1–17 doses), with 34 patients (85%)
receiving 2 doses or more. The safety profile in these pediatric patients was similar to that seen in adults; adverse reactions
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%), increased transaminases (28%), and hyponatremia (18%).
Merck’s Focus on Cancer
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our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the
largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through
strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve
the treatment of advanced cancers. For more information about our oncology clinical trials, visit
www.merck.com/clinicaltrials.
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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 2018 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 at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and
Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.
Media:
Pamela Eisele
(267) 305-3558
Kristen Drake
(908) 740-6179
Investors:
Teri Loxam
(908) 740-1986
Michael DeCarbo
(908) 740-1807
View source version on businesswire.com: https://www.businesswire.com/news/home/20190401005202/en/