FDA Approves Expanded Label for Merck’s KEYTRUDA® (pembrolizumab) in Combination with Pemetrexed (ALIMTA®)
and Platinum Chemotherapy for First-Line Treatment of Patients with Metastatic Nonsquamous NSCLC, with No EGFR or ALK Genomic Tumor
Aberrations
Approval Based on Results of KEYNOTE-189, Where KEYTRUDA in Combination with Pemetrexed and Platinum
Chemotherapy Reduced the Risk of Death by Half Compared to Chemotherapy Alone
Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration
(FDA) has approved an expanded label for KEYTRUDA®, Merck’s anti-PD-1 therapy, in combination with pemetrexed
(ALIMTA®) 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, based on results of the KEYNOTE-189 trial. In the pivotal,
Phase 3 KEYNOTE-189 trial of patients regardless of PD-L1 tumor expression status, KEYTRUDA in combination with pemetrexed and
platinum chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (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 progression-free survival (PFS) compared to chemotherapy alone (HR=0.52 [95% CI, 0.43-0.64];
p<0.00001). Data from KEYNOTE-189 support that KEYTRUDA is changing survival expectations for these patients.
“KEYTRUDA is rapidly becoming a foundation for the treatment of appropriate patients with metastatic non-small cell lung
cancer,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “Today’s approval of the expanded label for KEYTRUDA
based on data from the KEYNOTE-189 trial is an important milestone, and reinforces our steadfast commitment to improving survival
outcomes, and providing hope, for more patients with lung cancer.”
Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis,
hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic
hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, KEYTRUDA should be withheld or
discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related
reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more
information, see “Selected Important Safety Information” below.
“Over the last few years, we’ve seen significant clinical advances and an incredible shift in the way we approach the treatment
of people diagnosed with metastatic non-small cell lung cancer,” said Dr. Shirish Gadgeel, professor in thoracic oncology at the
University of Michigan Rogel Cancer Center. “As a practicing physician, I welcome today’s news, as KEYTRUDA in combination with
pemetrexed and platinum chemotherapy significantly prolonged overall survival and progression-free survival in the KEYNOTE-189
trial, compared with chemotherapy alone.”
KEYTRUDA in combination with pemetrexed and carboplatin was first approved in 2017 under the FDA’s accelerated approval process
for the first-line treatment of patients with metastatic nonsquamous NSCLC, based on tumor response rates and progression-free
survival data from the Phase 2 study (KEYNOTE-021, Cohort G1). In accordance with the accelerated approval process, continued
approval was contingent upon verification and description of clinical benefit, which has now been demonstrated in KEYNOTE-189 and
has resulted in the FDA converting the accelerated approval to full (regular) approval. KEYTRUDA is the first anti-PD-1 approved in
the first-line setting as both combination and monotherapy in certain patients with metastatic NSCLC (see KEYTRUDA indications
below).
Data Supporting the Approval
The approval was based on data from KEYNOTE-189, a Phase 3, randomized, multicenter, double-blind, active-controlled trial in
systemic-therapy naïve patients with metastatic NSCLC, regardless of PD-L1 tumor expression status and with no EGFR or ALK genomic
tumor aberrations. Patients with autoimmune disease that required systemic therapy within 2 years of treatment; a medical condition
that required immunosuppression; or patients who had received more than 30 Gy of thoracic radiation within the prior 26 weeks were
ineligible. Patients were randomized to receive KEYTRUDA 200 mg, cisplatin or carboplatin, and pemetrexed intravenously Q3W for 4
cycles followed by KEYTRUDA 200 mg for up to 24 months and pemetrexed Q3W (n=410); or cisplatin or carboplatin and pemetrexed
intravenously Q3W for 4 cycles followed by pemetrexed Q3W (n=206). Treatment continued until progression of disease or unacceptable
toxicity. Primary efficacy outcome measures were OS and PFS assessed by blinded independent central review (BICR) per RECIST v1.1
(modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ). Secondary efficacy outcome
measures were overall response rate (ORR) and duration of response (DOR). Patients receiving chemotherapy and pemetrexed who
experienced disease progression could cross over to receive KEYTRUDA as monotherapy. The KEYNOTE-189 study was conducted in
collaboration with Eli Lilly and Company, the makers of pemetrexed (ALIMTA®).
Efficacy Results in KEYNOTE-189
Endpoint |
|
|
|
|
KEYTRUDA
Pemetrexed
Platinum Chemotherapy
n=410
|
|
|
|
|
Placebo
Pemetrexed
Platinum Chemotherapy
n=206
|
OS |
Number (%) of patients with event |
|
|
|
|
127 (31%) |
|
|
|
|
108 (52%) |
Median in months (95% CI) |
|
|
|
|
NR
(NR, NR)
|
|
|
|
|
11.3
(8.7, 15.1)
|
Hazard ratio* (95% CI) |
|
|
|
|
0.49 (0.38, 0.64) |
p-Value† |
|
|
|
|
<0.00001 |
PFS |
Number of patients with event (%) |
|
|
|
|
244 (60%) |
|
|
|
|
166 (81%) |
Median in months (95% CI) |
|
|
|
|
8.8 (7.6, 9.2) |
|
|
|
|
4.9 (4.7, 5.5) |
Hazard ratio* (95% CI) |
|
|
|
|
0.52 (0.43, 0.64) |
p-Value† |
|
|
|
|
<0.00001 |
ORR |
Overall response rate‡ (95% CI) |
|
|
|
|
48% (43, 53) |
|
|
|
|
19% (14, 25) |
Complete response |
|
|
|
|
0.5% |
|
|
|
|
0.5% |
Partial response |
|
|
|
|
47% |
|
|
|
|
18% |
p-Value§ |
|
|
|
|
<0.0001 |
Duration of Response |
Median in months (range) |
|
|
|
|
11.2 (1.1+, 18.0+) |
|
|
|
|
7.8 (2.1+, 16.4+) |
* Based on the stratified Cox proportional hazard model
† Based on stratified log-rank test
‡ Response: Best objective response as confirmed complete response or partial
response
§ Based on Miettinen and Nurminen method stratified by PD-L1 status, platinum
chemotherapy and smoking status
NR = not reached
|
|
In KEYNOTE-189, safety was evaluated in 405 patients who received KEYTRUDA in combination with pemetrexed and platinum
chemotherapy and 202 patients who received placebo, pemetrexed, and platinum chemotherapy. KEYTRUDA was discontinued for adverse
reactions in 20 percent of patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were
pneumonitis (3%) and acute kidney injury (2%). Adverse reactions leading to the interruption of KEYTRUDA occurred in 53 percent of
patients; the most common adverse reactions or laboratory abnormalities leading to interruption of KEYTRUDA (≥5%) were neutropenia
(13%), asthenia/fatigue (7%), anemia (7%), and thrombocytopenia (5%). Adverse reactions of any grade occurring in at least 20
percent of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy were nausea (56%), fatigue (56%),
constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia
(20%).
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 750 trials studying
KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of
KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA,
including exploring several different biomarkers.
KEYTRUDA® (pembrolizumab) Indications and Dosing
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every
three weeks until disease progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with
metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations.
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.
In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without disease progression.
When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given
on the same day. See also the Prescribing Information for pemetrexed and carboplatin or cisplatin, as appropriate.
Head and Neck Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)
with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based
on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and
description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every
three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who
have relapsed after 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.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell
lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated
approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for the treatment of patients
with PMBCL who require urgent cytoreductive therapy.
In adults with PMBCL, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with PMBCL, KEYTRUDA is
administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity,
or up to 24 months in patients without disease progression.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not
eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [Combined Positive Score (CPS) ≥10] as determined by
an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This
indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for
this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have
disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment
with platinum-containing chemotherapy.
In locally advanced or metastatic urothelial carcinoma, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks
until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Microsatellite Instability-High (MSI-H) Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite
instability-high (MSI-H) or mismatch repair deficient (dMMR)
- solid tumors that have progressed following prior treatment and who have no satisfactory alternative
treatment options, or
- colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and
irinotecan.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued
approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been
established.
In adult patients with MSI-H cancer, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease
progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In children with MSI-H cancer,
KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or
unacceptable toxicity, or up to 24 months in patients without disease progression.
Gastric Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal
junction (GEJ) adenocarcinoma whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test,
with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing
chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for this indication may be contingent upon verification and
description of clinical benefit in the confirmatory trials. The recommended dose of KEYTRUDA is a fixed dose of 200 mg every three
weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Cervical Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or
after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under
accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in the confirmatory trials. The recommended dose of KEYTRUDA is a
fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity or up to 24 months in patients without
disease progression.
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 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 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 anti-hyperglycemics 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 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 Allogenic 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 developed graft-versus-host disease (GVHD)
(one fatal case) and 2 developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (one 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 clinical 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 clinical trials.
Embryofetal Toxicity
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.
Adverse Reactions
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-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-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-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, 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; one from GVHD after subsequent allogeneic HSCT and one 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%).
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%).
Lactation
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.
Pediatric Use
There is limited experience in pediatric patients. In a study in 40 pediatric patients with advanced melanoma, lymphoma, or
PD-L1–positive advanced, relapsed, or refractory solid tumors, the safety profile 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%).
Merck’s Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck,
the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is
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.
About the Merck Access Program for KEYTRUDA
At Merck, we are committed to supporting accessibility to our cancer medicines. Merck provides multiple programs to help ensure
that appropriate patients who are prescribed KEYTRUDA have access to our anti-PD-1 therapy. The Merck Access Program provides
reimbursement support for patients receiving KEYTRUDA, including information to help with out-of-pocket costs and co-pay assistance
for eligible patients. Merck also offers free product through our patient assistance program to eligible patients, primarily the
uninsured, who, without our assistance, could not afford their medicine. More information is available by calling 855-257-3932 or
visiting www.merckaccessprogram-keytruda.com.
About Merck’s Patient Support Program for KEYTRUDA
Merck is committed to helping provide patients and their caregivers support throughout their treatment with KEYTRUDA. The
KEY+YOU Patient Support Program provides a range of resources and services. For further information and to sign up, patients and
physicians may call 85-KEYTRUDA (855-398-7832) or visit www.keytruda.com.
About Merck
For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada,
has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. 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. Today, Merck continues to be at the forefront of research to advance the
prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic
diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola.
For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube 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 2017 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.
Merck
Media:
Doris Li, 908-246-5701
or
Kristen Drake, 908-334-4688
or
Investors:
Teri Loxam, 908-740-1986
or
Peter Dannenbaum, 908-740-1037
View source version on businesswire.com: https://www.businesswire.com/news/home/20180820005564/en/