Longest Follow-Up Data for KEYTRUDA in Lung Cancer to Date Showed
Five-Year Overall Survival Rate of 23.2% with KEYTRUDA in
Treatment-Naïve Patients and 15.5% in Previously Treated Patients with
Advanced NSCLC in KEYNOTE-001 Trial
Updated Overall Survival Analysis and New Data for Disease
Progression After Next-Line Treatment (Progression-Free Survival 2) from
KEYNOTE-189 Trial in Metastatic Nonsquamous NSCLC Also to be Presented
KENILWORTH, N.J.–(BUSINESS WIRE)–$MRK #ASCO–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced the presentation of five-year efficacy and safety data
for KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy in patients with
advanced non-small cell lung cancer (NSCLC) from the first KEYNOTE trial
(Phase 1b KEYNOTE-001). In this study, KEYTRUDA demonstrated a five-year
overall survival (OS) rate of 23.2% in treatment-naïve patients (n=101)
and 15.5% in previously treated patients (n=449). Of note, the five-year
OS rate among patients whose tumors expressed PD-L1 (tumor proportion
score [TPS] ≥50%) was 29.6% in treatment-naïve patients (n=27) and 25.0%
in previously treated patients (n=138). These findings, which represent
the longest follow-up for KEYTRUDA in lung cancer, will be highlighted
at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting
(Abstract #LBA9015) during the official press program and presented
during a poster discussion on Sunday, June 2.
“Lung cancer is the leading cause of cancer death, and historically, the
five-year survival rate has been around 5% for patients in the U.S. with
advanced non-small cell lung cancer,” said Edward B. Garon, MD, MS,
associate professor of medicine, Jonsson Comprehensive Cancer Center,
University of California, Los Angeles. “As a treating physician, it is
encouraging to see the results of KEYNOTE-001, in which pembrolizumab
showed a five-year overall survival rate of 23.2% in treatment-naïve
patients and 15.5% in previously treated patients.”
After 60.6 months (range, 51.8 to 77.9) of median follow-up, results
from KEYNOTE-001 demonstrated the effect of KEYTRUDA monotherapy across
primary and secondary endpoints, including OS, objective response rate
(ORR) and duration of response (DOR).
|
Events |
Median OS, mo |
60-mo OS |
|||||||
| Treatment-naïve | 75/101* | 22.3 (17.1-32.3) | 23.2 | ||||||
| TPS ≥50% | 17/27 | 35.4 (20.3-63.5) | 29.6 | ||||||
| TPS 1%-49% | 43/52 | 19.5 (10.7-26.3) | 15.7 | ||||||
| Previously treated | 375/449† | 10.5 (8.6-13.2) | 15.5 | ||||||
| TPS ≥50% | 104/138 | 15.4 (10.6-18.8) | 25.0 | ||||||
| TPS 1%-49% | 146/168 | 8.5 (6.0-12.6) | 12.6 | ||||||
| TPS <1% | 83/90 | 8.6 (5.5-10.6) | 3.5 |
*PD-L1 TPS <1% group not presented because of small patient numbers
(n=12).
†PD-L1 TPS was unknown in 53 patients.
The investigator-reported ORR was 41.6% (95% CI, 31.9-51.8) in
treatment-naïve patients and 22.9% (95% CI, 19.1-27.1) in previously
treated patients. Median DOR was 16.8 months (range, 2.1+ to 55.7+) and
38.9 months (range, 1.0+ to 71.8+), respectively.
Among the 60 patients who received two or more years of treatment with
KEYTRUDA, the five-year OS rate was 78.6% in treatment-naïve patients
and 75.8% in previously treated patients. The ORR in these patients was
86% and 91%, respectively. Median DOR was 52.0 months (range, 10.2 to
55.7+) in treatment-naïve patients and was not reached (range, 12.5 to
71.8+) in previously treated patients.
The safety profile of KEYTRUDA was consistent with what has been seen in
previously reported studies among patients with advanced NSCLC.
Treatment-related adverse events (TRAEs) of any grade occurred in 71%
(n=388) of patients receiving KEYTRUDA; grade 3-5 TRAEs occurred in 13%
(n=69) of patients. Immune-mediated adverse events were reported in 17%
(n=92) of patients. Hypothyroidism was the most commonly reported
immune-mediated adverse event, followed by pneumonitis, hyperthyroidism
and skin toxicities.
“Five-year survival is a significant milestone for patients with
advanced non-small cell lung cancer, and it is encouraging to see the
long-term overall survival rates from our first KEYNOTE study,” said Dr.
Roy Baynes, senior vice president and chief medical officer, Merck
Research Laboratories. “These five-year data provide important insights
into the long-term safety and efficacy of KEYTRUDA in patients with
advanced non-small cell lung cancer.”
Additional Lung Cancer Data from KEYNOTE-189 (Abstract #9013)
New and updated data from the Phase 3 KEYNOTE-189 trial evaluating
KEYTRUDA in combination with ALIMTA® (pemetrexed) and
platinum (cisplatin or carboplatin) for the first-line treatment of
metastatic nonsquamous NSCLC compared with pemetrexed plus platinum
alone, will also be presented on Sunday, June 2 at ASCO (Abstract
#9013). An updated analysis of the OS endpoint showed that after a
median follow-up of 18.7 months (range, 0.2 to 30.9), KEYTRUDA in
combination with pemetrexed-platinum chemotherapy reduced the risk of
death by 44% compared with chemotherapy alone (HR=0.56 [95% CI,
0.45-0.70]; median OS 22.0 months vs. 10.7 months). An improvement in
progression-free survival (PFS) was also observed, with a 52% reduction
in the risk of progression or death compared with chemotherapy alone
(HR=0.48 [95% CI, 0.40-0.58]; median PFS 9.0 months vs. 4.9 months).
Fifty four percent of patients in the chemotherapy alone arm received
subsequent immunotherapy, including 41% who received in-study crossover.
New findings at ASCO from KEYNOTE-189 also include the first-time
presentation of the progression-free survival 2 (PFS2) study endpoint, a
clinical endpoint used to assess the impact of next-line treatment on
disease control, in the entire study population and different PD-L1
subgroups. Among patients who received KEYTRUDA in combination with
chemotherapy, findings showed a 51% reduction in risk from time of
randomization to objective tumor progression on next-line treatment or
death from any cause, whichever comes first, compared with patients who
received chemotherapy alone (HR=0.49 [95% CI, 0.40-0.59]; median PFS2
17.0 months vs. 9.0 months). Results were consistent across all three
PD-L1 categories evaluated – with a 54% reduction in patients with a TPS
<1% (HR=0.46 [95% CI, 0.33-0.66]), a 41% reduction in patients with a
TPS of 1-49% (HR=0.59 [95% CI, 0.41-0.86]), and a 53% reduction in
patients with a TPS ≥50% (HR=0.47 [95% CI, 0.33-0.69]).
Grade 3-5 adverse events from any cause occurred in 71.9% (n=291) of
patients who received KEYTRUDA in combination with chemotherapy and
66.8% (n=135) in the chemotherapy alone arm. Adverse events leading to
discontinuation of any treatment component occurred in 33.6% (n=136) of
patients who received KEYTRUDA in combination with chemotherapy and
16.3% (n=33) in the chemotherapy alone arm. There were two deaths in the
KEYTRUDA combination arm from immune-mediated adverse events and
infusion reactions. KEYNOTE-189 was conducted in collaboration with Eli
Lilly and Company, the makers of pemetrexed (ALIMTA®).
Study Design of KEYNOTE-001 (Abstract #LBA9015)
KEYNOTE-001 (ClinicalTrials.gov, NCT01295827)
is a Phase 1b multicenter, open-label, multi-cohort trial evaluating
KEYTRUDA in various advanced cancers, including 550 patients with either
treatment-naïve or previously treated advanced NSCLC. Patients received
2 mg/kg or 10 mg/kg of KEYTRUDA every three weeks (Q3W) or 10 mg/kg of
KEYTRUDA every two weeks until unacceptable toxicity or disease
progression. The primary endpoint was ORR; secondary endpoints included
PFS, OS and DOR.
Study Design of KEYNOTE-189 (Abstract #9013)
KEYNOTE-189 (ClinicalTrials.gov, NCT02578680)
is a pivotal Phase 3, randomized, double-blind, placebo-controlled trial
of 616 untreated patients with metastatic nonsquamous NSCLC and no EGFR
or ALK genomic tumor aberrations 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 were randomized 2:1 to receive KEYTRUDA 200 mg,
cisplatin or carboplatin, and pemetrexed intravenously Q3W for four
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 four cycles followed by pemetrexed Q3W (n=206). Treatment
continued until progression of disease or unacceptable toxicity. The
dual primary endpoints were OS and PFS; secondary endpoints included ORR
and DOR.
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% of all cases.
Small cell lung cancer (SCLC) accounts for about 10 to 15% of all lung
cancers. Between 2008 and 2014, the five-year survival rate for patients
diagnosed in the U.S. with advanced NSCLC was only 5%. Moreover,
approximately 50% of metastatic NSCLC patients in the U.S. will not
receive second-line therapy.
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 1,000 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
paclitaxel protein-bound, 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 stage III NSCLC who are not candidates for surgical
resection or definitive chemoradiation, or metastatic NSCLC, and whose
tumors express PD-L1 [tumor proportion score (TPS) ≥1%] 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 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 200 mg
is 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.
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 200 mg is 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. 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 200 mg is 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. 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 200 mg
is 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.
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 200 mg is 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. In pediatric patients 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 200 mg 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.
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 200 mg 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.
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 200 mg 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.
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.
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line
treatment of patients with advanced renal cell carcinoma. In renal cell
carcinoma, KEYTRUDA 200 mg is administered as an intravenous infusion
over 30 minutes every 3 weeks in combination with 5 mg axitinib orally
twice daily until disease progression, unacceptable toxicity, or for
KEYTRUDA, up to 24 months in patients without disease progression. When
axitinib is used in combination with KEYTRUDA, dose escalation of
axitinib above the initial 5 mg dose may be considered at intervals of
six weeks or longer. See also the Prescribing Information for
recommended axitinib dosing information.
Selected Important Safety Information for KEYTRUDA (pembrolizumab)
Injection, 100mg
Immune-Mediated Pneumonitis
KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases.
Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers
receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4
(0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC
patients receiving KEYTRUDA as a single agent, including Grades 3-4 in
3.2% of patients, and occurred more frequently in patients with a
history of prior thoracic radiation (17%) compared to those without
(7.7%).
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, or Hepatoxicity (in Combination With
Axitinib)
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.
Contacts
Media Contacts:
Pamela Eisele
(267) 305-3558
Justine Moore
(347) 281-3754
Investor Contacts:
Teri Loxam
(908) 740-1986
Michael DeCarbo
(908) 740-1807