FDA Approves Merck’s KEYTRUDA® (pembrolizumab) as Monotherapy for Patients with Metastatic Small Cell Lung Cancer (SCLC) with Disease Progression on or After Platinum-Based Chemotherapy and at Least One Other Prior Line of Therapy

Marks First Approval for KEYTRUDA in SCLC

KENILWORTH, N.J.–(BUSINESS WIRE)–$MRK #MRK–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 KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the
treatment of patients with metastatic small cell lung cancer (SCLC) with
disease progression on or after platinum-based chemotherapy and at least
one other prior line of therapy. This accelerated approval is 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. This marks the first
indication for KEYTRUDA in SCLC.

KEYTRUDA is already an established treatment option for non-small cell
lung cancer, and today’s approval in small cell lung cancer demonstrates
our commitment to bringing forward new treatment options for patients
with advanced, difficult-to-treat cancers,” said Dr. Jonathan Cheng,
vice president, oncology clinical research, Merck Research Laboratories.
We look forward to continuing to advance important clinical research in
small cell lung cancer.”

Immune-mediated adverse reactions, which may be severe or fatal, can
occur with KEYTRUDA, including pneumonitis, colitis, hepatitis,
endocrinopathies, nephritis and renal dysfunction, 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.

Small cell lung cancer, which accounts for 10 to 15% of all lung
cancers, is often diagnosed at an advanced stage where the prognosis is
very poor and there have historically been limited treatment options,”
said Dr. Patrick Ott, MD, PhD, clinical director, Center for
Immuno-Oncology, Dana-Farber Cancer Institute. “The approval of KEYTRUDA
in small cell lung cancer provides an additional treatment option for
patients based on the clinical response rates from KEYNOTE-158 and
KEYNOTE-028.”

About KEYNOTE-158 and KEYNOTE-028

The approval was based on pooled data from KEYNOTE-158 (cohort G) and
KEYNOTE-028 (cohort C1), two multicenter, multi-cohort, non-randomized,
open-label trials evaluating KEYTRUDA in patients with SCLC who had
disease progression on or after platinum-based chemotherapy and at least
one other prior line of therapy. The trials excluded patients with
autoimmune disease or a medical condition that required
immunosuppression. Among the 83 patients enrolled in the trials and who
were evaluated for efficacy, 64% received two prior lines of therapy and
36% received three or more lines of therapy; 60% received prior thoracic
radiation therapy; 51% received prior radiation therapy to the brain.

Patients evaluated for efficacy received either KEYTRUDA 200 mg
intravenously every three weeks (n=64) or 10 mg/kg intravenously every
two weeks (n=19). Treatment with KEYTRUDA continued until documented
disease progression, unacceptable toxicity or a maximum of 24 months.
Patients with initial radiographic disease progression could receive
additional doses of KEYTRUDA during confirmation of progression unless
disease progression was symptomatic, was rapidly progressive, required
urgent intervention or occurred with a decline in performance status.
The major efficacy outcome measures were objective response rate (ORR)
and duration of response (DOR) as assessed by BICR according to 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.

KEYTRUDA demonstrated an ORR of 19% (95% CI, 11-29), with a complete
response rate of 2% and a partial response rate of 17%. Among the 16
responding patients, 94% had a DOR of six months or longer, 63% had a
DOR of 12 months or longer and 56% had a DOR of 18 months or longer.
Responses ranged from 4.1 to 35.8+ months.

Among the patients with SCLC enrolled in KEYNOTE-158 (cohort G) (n=107)
and KEYNOTE-028 (cohort C1) (n=24) who were included in the safety
analysis, the adverse reactions that occurred were similar to those
occurring in patients with other solid tumors who received KEYTRUDA as a
single agent.

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 benefiting
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.

Non-Small Cell 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 NSCLC expressing PD-L1 [tumor proportion score (TPS)
≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic
tumor aberrations, and is stage III where patients are not candidates
for surgical resection or definitive chemoradiation, or metastatic.

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.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic
small cell lung cancer (SCLC) with disease progression on or after
platinum-based chemotherapy and at least one other prior line 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. In SCLC, 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.

Head and Neck Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is
indicated for the first-line treatment of patients with metastatic or
with unresectable, recurrent head and neck squamous cell carcinoma
(HNSCC).

KEYTRUDA, as a single agent, is indicated for the first line treatment
of patients with metastatic or unresectable, recurrent HNSCC whose
tumors express PD-L1 [combined positive score (CPS) ≥1] as determined by
an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients
with recurrent or metastatic HNSCC with disease progression on or after
platinum-containing chemotherapy.

In HNSCC, the recommended dose of KEYTRUDA is 200 mg administered as an
intravenous infusion over 30 minutes every 3 weeks until disease
progression, unacceptable toxicity, or up to 24 months in patients
without disease progression.

When administering KEYTRUDA in combination with chemotherapy, administer
KEYTRUDA prior to chemotherapy when given on the same day. Refer to the
Prescribing Information for the chemotherapy agents administered in
combination with KEYTRUDA for recommended dosing information, as
appropriate.

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 [
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 (RCC). In RCC,
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

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%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving
KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients,
and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in
combination with platinum and FU as first-line therapy for advanced
disease, including Grade 3-5 in 1.5% of patients.

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) and Hepatotoxicity (KEYTRUDA 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.

Hepatotoxicity in Combination with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with
higher than expected frequencies of Grades 3 and 4 ALT and AST
elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA
and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%)
were seen. Monitor liver enzymes before initiation of and periodically
throughout treatment. Consider more frequent monitoring of liver enzymes
as compared to when the drugs are administered as single agents. For
elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider
administering corticosteroids as needed.

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 1185 patients with HNSCC (16%), receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. 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.

Contacts

Media:
Pamela Eisele
(267) 305-3558

Justine Moore
(347) 281-3754

Investors:
Teri Loxam
(908) 740-1986

Michael DeCarbo
(908) 740-1807

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