Data for Merck’s KEYTRUDA® (pembrolizumab) Across Different Types of Advanced Lung Cancer Presented at AACR Annual Meeting 2019
April 1, 2019First Presentation of Overall Survival Data from Post-Hoc Analysis of
KEYNOTE-189 in Patients with Advanced Nonsquamous Non-Small Cell Lung
Cancer Who Have Liver or Brain Metastases
Pooled Data in Patients with Previously Treated Advanced Small Cell
Lung Cancer in AACR 2019 Plenary Session and Press Conference
KENILWORTH, N.J.–(BUSINESS WIRE)—-Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the first-time presentation of results from a post-hoc
analysis of patients with liver or brain metastases from the Phase 3
KEYNOTE-189 trial. This post-hoc analysis from KEYNOTE-189, which
evaluated KEYTRUDA in combination with pemetrexed (ALIMTA®)
and cisplatin or carboplatin in patients with advanced nonsquamous
non-small cell lung cancer (NSCLC) regardless of PD-L1 tumor expression
and with no EGFR or ALK genomic tumor aberrations, was featured in an
oral presentation (Abstract #CT043) at the American Association for
Cancer Research (AACR) Annual Meeting 2019 in Atlanta, Georgia.
Additionally, pooled data from the Phase 2 KEYNOTE-158 and Phase 1b
KEYNOTE-028 trials evaluating KEYTRUDA in patients with previously
treated advanced small cell lung cancer (SCLC) will be highlighted today
in the AACR plenary session and press conference (Abstract #CT073). Data
from KEYNOTE-158 and KEYNOTE-028 supported Merck’s first application in
SCLC for KEYTRUDA. This supplemental Biologics License Application
(sBLA) was accepted by the U.S. Food and Drug Administration (FDA) for
priority review, with a Prescription Drug User Fee Act (PDUFA), or
target action, date of June 17, 2019.
“At this year’s AACR meeting, we are pleased to share important data
from our broad clinical development program in lung cancer, as we
continue to understand the effects of KEYTRUDA in subsets of patients
with advanced lung cancer whose disease has been traditionally difficult
to treat,” said Dr. Jonathan Cheng, vice president, oncology clinical
research, Merck Research Laboratories.
Liver and Brain Metastases Data from KEYNOTE-189 (Abstract #CT043)
KEYNOTE-189 was a pivotal Phase 3, randomized, double-blind,
placebo-controlled study of 616 untreated patients with metastatic
nonsquamous NSCLC designed to evaluate the efficacy of KEYTRUDA in
combination with pemetrexed and cisplatin or carboplatin (n=410),
compared with pemetrexed and cisplatin or carboplatin alone (n=206).
Patients had no sensitizing EGFR or ALK genomic tumor aberrations and
had not previously received systemic therapy for advanced disease. The
dual primary endpoints were overall survival (OS) and progression-free
survival (PFS); secondary endpoints included overall response rate (ORR)
and duration of response (DOR). In the primary analysis of KEYNOTE-189
presented at AACR 2018, which included patients regardless of PD-L1
expression status, 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).
The objective of this post-hoc analysis was to evaluate outcomes of
KEYTRUDA in combination with chemotherapy in patients with liver (16%;
n=66) or brain metastases (18%; n=73) at baseline. The median follow-up
of this analysis was 18.7 months. The findings showed KEYTRUDA in
combination with chemotherapy reduced the risk of death by 38 percent
(HR=0.62 [95% CI, 0.39-0.98]) in patients with liver metastases and by
59 percent (HR=0.41 [95% CI, 0.24-0.67]) in patients with brain
metastases compared to chemotherapy alone. KEYTRUDA in combination with
chemotherapy also improved PFS, with a reduction in the risk of
progression or death by 48 percent (HR=0.52 [95% CI, 0.34-0.81]) in
patients with liver metastases and 58 percent (HR=0.42 [95% CI,
0.27-0.67]) in patients with brain metastases compared to chemotherapy
alone. It is important to note that these analyses were not controlled
for multiplicity.
“In patients with advanced non-small cell lung cancer who have liver or
brain metastases, the prognosis has been historically poor,” said Dr.
Marina Garassino, Istituto Nazionale dei Tumori, Milan, Italy. “In this
post-hoc analysis, KEYTRUDA in combination with chemotherapy provided an
overall survival and progression-free survival benefit compared with
chemotherapy alone, irrespective of liver or brain metastases at
baseline. These exploratory findings are consistent with the overall
results of the KEYNOTE-189 trial.”
| Post-Hoc Analysis Results from KEYNOTE-189 | |||||||||||||||||||||||||||
| PFS | OS | ||||||||||||||||||||||||||
| N* |
Median, |
HR
|
Median, |
HR
|
|||||||||||||||||||||||
|
Patients |
KEYTRUDA |
66 |
6.1 |
0.52
|
12.6 |
0.62
|
|||||||||||||||||||||
|
Placebo |
49 |
3.4 |
6.6 |
||||||||||||||||||||||||
|
Patients |
KEYTRUDA |
344 |
9.2 |
0.48
|
23.7 |
0.58
|
|||||||||||||||||||||
|
Placebo |
157 |
5.4 |
13.2 |
||||||||||||||||||||||||
|
Patients |
KEYTRUDA |
73 |
6.9 |
0.42
|
19.2 |
0.41
|
|||||||||||||||||||||
|
Placebo |
35 |
4.7 |
7.5 |
||||||||||||||||||||||||
|
Patients |
KEYTRUDA |
337 |
9.2 |
0.48
|
22.4 |
0.59
|
|||||||||||||||||||||
|
Placebo |
171 |
4.9 |
12.1 |
||||||||||||||||||||||||
| *25 patients had both liver and brain metastases | |||||||||||||||||||||||||||
No new safety signals were identified in this exploratory analysis in
those with liver or brain metastases. KEYNOTE-189 was conducted in
collaboration with Eli Lilly and Company, the makers of pemetrexed
(ALIMTA®).
Data in Small Cell Lung Cancer (Abstract #CT073)
KEYNOTE-158 and KEYNOTE-028 are two open-label, non-randomized,
multi-cohort studies evaluating KEYTRUDA monotherapy in patients with
multiple types of advanced solid tumors that progressed on standard of
care therapy – including SCLC. KEYNOTE-158 includes patients with
advanced SCLC regardless of PD-L1 tumor expression and KEYNOTE-028
includes patients with SCLC whose tumors express PD-L1 (combined
positive score [CPS] ≥1). The primary endpoint in both studies was ORR;
secondary endpoints include PFS, OS and DOR. Median follow-up was 7.7
months (range, 0.5 to 48.7).
In the pooled analysis of data from KEYNOTE-158 (n=64) and KEYNOTE-028
(n=19), patients whose disease progressed after two or more lines of
prior therapy received KEYTRUDA. In the study, KEYTRUDA demonstrated an
ORR of 19.3 percent (95% CI, 11.4-29.4), with two complete responses and
14 partial responses as assessed by blinded independent central review
(BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1,
modified to follow a maximum of 10 target lesions and a maximum of five
target lesions per organ. More than half (n=9/16) of the patients had a
duration of response that lasted 18 months or longer. Median DOR was not
reached (range, 4.1 to 35.8+). Median OS was 7.7 months (95% CI,
5.2-10.1) with 12- and 24-month OS rates of 34.3 percent and 20.7
percent, respectively. Median PFS was 2.0 months (95% CI, 1.9-3.4) with
12- and 24-month PFS rates of 16.9 percent and 13.1 percent,
respectively.
No new safety signals were identified in this
analysis. Treatment-related adverse events (TRAEs) of any grade occurred
in 61 percent of patients with two or more prior lines of therapy. Grade
5 TRAEs that led to death occurred in two patients with two or more
prior lines of therapy. Immune-mediated adverse events or infusion
reactions occurred in 24 percent of patients with two or more prior
lines of therapy.
About Lung Cancer
Lung cancer, which forms in the tissues of the lungs, usually within
cells lining the air passages, is the leading cause of cancer death
worldwide. Each year, more people die of lung cancer than die of colon
and breast cancers combined. 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. Small cell lung cancer (SCLC) accounts for about 10 to 15 percent
of all lung cancers. The five-year survival rates for
patients diagnosed in the United States with any stage of NSCLC or SCLC
are estimated to be 23 percent and six percent, respectively.
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
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
- solid tumors that have progressed following prior treatment and who
-
- colorectal cancer that has progressed following treatment with
fluoropyrimidine, oxaliplatin, and irinotecan.
- colorectal cancer that has progressed following treatment with
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 [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 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.
Contacts
Media Contacts:
Pamela Eisele
(267) 305-3558
Kristen Drake
(908) 740-1679
Investor Contacts:
Teri Loxam
(908) 740-1986
Michael DeCarbo
(908) 740-1807