Market Overview

New Data from Merck's Leading Immuno-Oncology Clinical Development Program in Over 25 Tumor Types to Be Presented at 2018 ASCO Annual Meeting

Share:

New and Long-term Overall Survival Data for KEYTRUDA®
(pembrolizumab) in Lung Cancer and Melanoma, Plus New Data in Renal
Cell, Cervical, Merkel Cell, and Other Cancers

First-Time Lynparza® (olaparib) Data in
Combination with Abiraterone in Metastatic Prostate Cancer Under Merck
and AstraZeneca Strategic Collaboration

New Data in Four Tumor Types Evaluating LENVIMA®
(lenvatinib) in Combination with KEYTRUDA Under Merck and Eisai
Strategic Collaboration

Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced that new combination and monotherapy data from Merck's
oncology portfolio, anchored by anti-PD-1 therapy KEYTRUDA, will be
presented at the 54th Annual Meeting of the American Society
of Clinical Oncology (ASCO) in Chicago from June 1-5. More than 140
abstracts in over 25 tumor types have been accepted, including new and
long-term data for KEYTRUDA across multiple types of cancer.

"With more data and longer follow-up across tumors and treatment
settings, evidence continues to support the role of KEYTRUDA as a
foundational treatment for many types of cancer," said Dr. Roger M.
Perlmutter, president, Merck Research Laboratories. "At ASCO, we will
present new and long-term overall survival data for KEYTRUDA in advanced
lung cancer and melanoma – as well as studies across our growing
oncology portfolio in a number of new tumor types where we have adduced
clinically meaningful results."

The abstracts accepted for the 2018 ASCO Annual Meeting include data for
approved and investigational uses of KEYTRUDA, investigational uses of
PARP inhibitor Lynparza and MEK inhibitor selumetinib (in collaboration
with AstraZeneca), and investigational uses of kinase inhibitor LENVIMA
(in collaboration with Eisai). Highlights to be presented at ASCO
include:

Select Lung Cancer Presentations

  • New overall survival (OS) data from the pivotal Phase 3 KEYNOTE-042
    trial with KEYTRUDA monotherapy compared to chemotherapy alone as
    first-line treatment in patients with locally advanced or metastatic
    nonsquamous or squamous non-small cell lung cancer (NSCLC) with a
    PD-L1 tumor proportion score (TPS) of ≥1 percent are to be presented
    in the ASCO opening plenary session and press program on Sunday, June
    3 (Abstract #LBA4). As previously announced, an interim
    analysis conducted by the independent Data Monitoring Committee (DMC)
    demonstrated that treatment with KEYTRUDA monotherapy resulted in
    significantly longer overall survival (OS) than that achieved with
    platinum-based chemotherapy (carboplatin plus paclitaxel or
    carboplatin plus pemetrexed) in patients with a PD-L1 TPS of ≥1
    percent.
  • First-time data of an early patient cohort (n=204) from the
    randomized, double-blind, placebo-controlled, Phase 3 KEYNOTE-407
    trial investigating KEYTRUDA in combination with
    carboplatin-paclitaxel or nab-paclitaxel, compared with
    carboplatin-paclitaxel or nab-paclitaxel alone as first-line treatment
    in patients with metastatic squamous NSCLC (Abstract #105) are to be
    presented. An interim analysis of pre-specified secondary endpoints
    showed an alpha-controlled, overall response rate (ORR) of 58.4
    percent for KEYTRUDA plus chemotherapy (n=101) compared to 35 percent
    for chemotherapy alone (n=103) (p-value, 0.0004) [(7.7 months median
    follow-up (range 0.4, 13.9)]. The duration of response (DOR) was ≥6
    months in 65.8 percent of patients receiving KEYTRUDA plus
    chemotherapy compared to 45.6 percent receiving chemotherapy alone.
    Adverse events (grade ≥3) were 64.4 percent for KEYTRUDA plus
    chemotherapy and 74.5 percent for chemotherapy alone. No new safety
    concerns were reported. The primary endpoints of the study are OS and
    progression-free survival (PFS). As previously announced, based on
    these data, Merck has recently submitted a supplemental Biologics
    License Application (sBLA) to the U.S. Food and Drug Administration
    (FDA).

Select Combination Data Presentations

  • First-time data from a Phase 2 trial in post-chemotherapy, metastatic
    castration-resistant prostate cancer with Lynparza in combination with
    standard of care, abiraterone, regardless of HRRm status (Abstract
    #5003) are to be featured as an oral presentation. This is the first
    data for a PARP inhibitor in combination with standard of care,
    abiraterone, in the treatment of prostate cancer.
  • New and updated data for KEYTRUDA in combination with LENVIMA are to
    be presented including in advanced hepatocellular carcinoma (HCC),
    endometrial carcinoma, head and neck squamous cell carcinoma (HNSCC)
    and renal cell carcinoma (RCC) from the KEYNOTE-524 (Study 111) and
    Phase 1b/2 KEYNOTE-526 (Study 116) studies (Abstracts #4076, #5596,
    #6016 and #4560, respectively). KEYTRUDA in combination with LENVIMA
    was previously granted Breakthrough Therapy Designation for the
    potential treatment of advanced and/or metastatic RCC.

Select Monotherapy Data Presentations

  • Long-term (four- and five-year) OS data from KEYNOTE-006 and
    KEYNOTE-001 in advanced melanoma with KEYTRUDA monotherapy (Abstracts
    #9503 and #9516, respectively) are to be presented.
  • First-time and long-term data for KEYTRUDA monotherapy are to be
    presented in eight tumor types. These data are in esophageal cancer
    (KEYNOTE-180, Abstract #4049), HCC (KEYNOTE-224, Abstract #4020),
    Merkel cell carcinoma (KEYNOTE-017, Abstract #9506), RCC (KEYNOTE-427,
    Abstract #4500), prostate cancer (KEYNOTE-199, Abstract #5007),
    ovarian cancer (KEYNOTE-100, Abstract #5511), cervical cancer
    (KEYNOTE-158, Abstract #5522) and small cell lung cancer (KEYNOTE-158,
    Abstract #8506).

Merck Investor Event

Merck will hold an investor event in conjunction with the 2018 ASCO
Annual Meeting on Monday, June 4 at 5:45 p.m. CT. Those unable to attend
in person will be able to listen to a live audio webcast of the
presentation. Details of the event will be provided at a date closer to
the event at http://investors.merck.com/home/default.aspx.

Details on Merck's Late-Breaking, Oral and Clinical Science Symposium
ASCO Abstracts

Late-Breaking Presentation

  • Abstract #LBA4 Late-Breaking Presentation: Pembrolizumab (pembro)
    versus platinum-based chemotherapy (chemo) as first-line therapy for
    advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥
    1%: Open-label, phase 3 KEYNOTE-042 study. G. Lopes. Sunday, June 3.
    3:10-3:25 p.m. CT. Location: Hall B1.

Oral Presentations

  • Abstract #4062 Oral Session: Pembrolizumab (pembro) vs paclitaxel
    (PTX) for previously treated advanced gastric or gastroesophageal
    junction (G/GEJ) cancer: Phase 3 KEYNOTE-061 trial. C. Fuchs. Monday,
    June 4. 5:24-5:36 p.m. CT. Location: Arie Crown Theater.
  • Abstract #4500 Oral Session: Pembrolizumab monotherapy as first-line
    therapy in advanced clear cell renal cell carcinoma (accRCC): Results
    from cohort A of KEYNOTE-427. D. McDermott. Sunday, June 3. 8-8:12
    a.m. CT. Location: Arie Crown Theater.
  • Abstract #5003 Oral Session: Olaparib combined with abiraterone in
    patients (pts) with metastatic castration-resistant prostate cancer
    (mCRPC): A randomized phase II trial. N. Clarke. Monday, June 4.
    4-4:12 p.m. CT. Location: Hall D1.
  • Abstract #5007 Oral Session: KEYNOTE-199: Pembrolizumab (pembro) for
    docetaxel-refractory metastatic castration-resistant prostate cancer
    (mCRPC). J. De Bono. Monday, June 4. 5:12-5:24 p.m. CT. Location: Hall
    D1.
  • Abstract #8506 Oral Session: Phase 2 study of pembrolizumab in
    advanced small-cell lung cancer (SCLC): KEYNOTE-158. H. Chung. Monday,
    June 4. 10-10:12 a.m. CT. Location: Hall B1.
  • Abstract #9503 Oral Session: 4-year survival and outcomes after
    cessation of pembrolizumab (pembro) after 2-years in patients (pts)
    with ipilimumab (ipi)-naive advanced melanoma in KEYNOTE-006. G. Long.
    Monday, June 4. 9-9:12 a.m. CT. Location: Arie Crown Theater.
  • Abstract #9506 Oral Session: Durable tumor regression and overall
    survival (OS) in patients with advanced Merkel cell carcinoma (aMCC)
    receiving pembrolizumab as first-line therapy. P. Nghiem. Monday, June
    4. 10-10:12 a.m. CT. Location: Arie Crown Theater.
  • Abstract #10503 Oral Session: SPRINT: Phase II study of the MEK 1/2
    inhibitor selumetinib (AZD6244, ARRY-142886) in children with
    neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas
    (PN). A. Gross. Saturday, June 2. 4-4:12 p.m. CT. Location: S504.

Clinical Symposium Presentations

  • Abstract #105 Clinical Science Symposium: Phase 3 study of
    carboplatin-paclitaxel/nab-paclitaxel (Chemo) with or without
    pembrolizumab (Pembro) for patients (Pts) with metastatic squamous
    (Sq) non-small cell lung cancer (NSCLC). L. Paz-Ares. Sunday, June 3.
    10:09-10:21 a.m. CT. Location: Hall D1.
  • Abstract #106 Clinical Science Symposium: TOPACIO/KEYNOTE-162
    (NCT02657889): A phase 1/2 study of niraparib + pembrolizumab in
    patients (pts) with advanced triple-negative breast cancer or
    recurrent ovarian cancer (ROC)—Results from ROC cohort. P.
    Konstantinopoulos. Sunday, June 3. 10:21-10:33 a.m. CT. Location: Hall
    D1.
  • Abstract #108 Clinical Science Symposium: Epacadostat (E) plus
    pembrolizumab (P) versus pembrolizumab alone in patients (pts) with
    unresectable or metastatic melanoma: Results of the phase 3
    ECHO-301/KEYNOTE-252 study. G. Long. Sunday, June 3. 10:33-10:45 a.m.
    CT. Location: Hall D1.
  • Abstract #1011 Clinical Science Symposium: TOPACIO/KEYNOTE-162:
    Niraparib + pembrolizumab in patients (pts) with metastatic
    triple-negative breast cancer (TNBC), a phase 2 trial. S. Vinayak.
    Monday, June 4. 3:36-3:48 p.m. CT. Location: Hall D2.
  • Abstract #5511 Clinical Science Symposium: Antitumor activity and
    safety of pembrolizumab in patients with advanced recurrent ovarian
    cancer: Interim results from the phase 2 KEYNOTE-100 study. U.
    Matulonis. Sunday, June 3. 10:21-10:33 a.m. CT. Location: S406.

For more information, including a complete list of abstract titles and
presentation dates and times for Merck's oncology portfolio, please
visit the ASCO website at https://iplanner.asco.org/am2018.

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, which currently involves 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 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, 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
(pembrolizumab).

KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated
for the first-line treatment of patients with metastatic nonsquamous
NSCLC. This indication is approved under accelerated approval based on
tumor response rate and progression-free survival. Continued approval
for this indication may be contingent upon verification and description
of clinical benefit in the confirmatory trials.

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.

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 (pembrolizumab) 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 who are not eligible for
cisplatin-containing chemotherapy. 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 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 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 (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases.
Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA,
including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%)
pneumonitis, 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.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48
(1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3
(1.1%), and 4 (<0.1%) colitis. 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.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19
(0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3
(0.4%), and 4 (<0.1%) hepatitis. 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.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of
2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%),
and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of
hypophysitis (including hypopituitarism and adrenal insufficiency).
Administer corticosteroids and hormone replacement as clinically
indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for
Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism,
hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%)
of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3
(0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799
patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%)
hypothyroidism. The incidence of new or worsening hypothyroidism was
higher in patients with HNSCC, occurring in 28 (15%) of 192 patients
with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis
occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including
Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid
function (at the start of treatment, periodically during treatment, and
as indicated based on clinical evaluation) and for clinical signs and
symptoms of thyroid disorders. Administer replacement hormones for
hypothyroidism and manage hyperthyroidism with thionamides and
beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade
3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic
ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients.
Monitor patients for hyperglycemia or other signs and symptoms of
diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA
and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9
(0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3
(0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal
function. Administer corticosteroids for Grade 2 or greater nephritis.
Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for
Grade 3 or 4 nephritis.

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.

KEYTRUDA can cause other clinically important immune-mediated adverse
reactions. These immune-mediated reactions may occur in any organ
system. 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, and partial seizures
arising in a patient with inflammatory foci in brain parenchyma. In
addition, myelitis and myocarditis were reported in other clinical
trials, including classical Hodgkin lymphoma, and postmarketing use.

Solid organ transplant rejection has been reported in postmarketing use
of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection
in solid organ transplant recipients. Consider the benefit of treatment
with KEYTRUDA vs the risk of possible organ rejection in these patients.

KEYTRUDA can cause severe or life-threatening infusion-related
reactions, including hypersensitivity and anaphylaxis, which have been
reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and
symptoms of infusion-related reactions, including rigors, chills,
wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever.
For Grade 3 or 4 reactions, stop infusion and permanently discontinue
KEYTRUDA.

Immune-mediated complications, including fatal events, occurred in
patients who underwent allogeneic hematopoietic stem cell
transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients
with cHL who proceeded to allogeneic HSCT after treatment with KEYTRUDA
on any trial, 6 patients (26%) developed graft-versus-host disease
(GVHD), one of which was fatal, and 2 patients (9%) developed severe
hepatic veno-occlusive disease (VOD) after reduced-intensity
conditioning, one of which was fatal. 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.

These complications may occur despite intervening therapy between PD-1
blockade and allogeneic HSCT. Follow patients closely for early evidence
of transplant-related complications such as hyperacute GVHD, severe
(Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic
VOD, and other immune-mediated adverse reactions, and intervene promptly.

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.

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.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9%
of 555 patients with advanced melanoma; adverse reactions leading to
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%). Adverse reactions leading to interruption of
KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea
(2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab
were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs
23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are
listed for ipilimumab only for those adverse reactions that occurred at
the same or lower rate than with KEYTRUDA.

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%). Adverse reactions leading to interruption of
KEYTRUDA occurred in 23% of patients; the most common (≥1%) were
diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation
(1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common
adverse reactions (occurring in at least 20% of patients and at a higher
incidence than with docetaxel) were decreased appetite (25% vs 23%),
dyspnea (23% vs 20%), and nausea (20% vs 18%).

In KEYNOTE-021(G1), when KEYTRUDA was administered in combination with
carboplatin and pemetrexed (carbo/pem) in advanced nonsquamous NSCLC,
KEYTRUDA was discontinued in 10% of 59 patients. The most common adverse
reaction resulting in discontinuation of KEYTRUDA (≥2%) was acute kidney
injury (3.4%). Adverse reactions leading to interruption of KEYTRUDA
occurred in 39% of patients; the most common (≥2%) were fatigue (8%),
neutrophil count decreased (8%), anemia (5%), dyspnea (3.4%), and
pneumonitis (3.4%). The most common adverse reactions (≥20%) with
KEYTRUDA compared to carbo/pem alone were fatigue (71% vs 50%), nausea
(68% vs 56%), constipation (51% vs 37%), rash (42% vs 21%), vomiting
(39% vs 27%), dyspnea (39% vs 21%), diarrhea (37% vs 23%), decreased
appetite (31% vs 23%), headache (31% vs 16%), cough (24% vs 18%),
dizziness (24% vs 16%), insomnia (24% vs 15%), pruritus (24% vs 4.8%),
peripheral edema (22% vs 18%), dysgeusia (20% vs 11%), alopecia (20% vs
3.2%), upper respiratory tract infection (20% vs 3.2%), and arthralgia
(15% vs 24%). This study was not designed to demonstrate a statistically
significant difference in adverse reaction rates for KEYTRUDA as
compared to carbo/pem alone for any specified adverse reaction.

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 (reported in at least 20% of patients) 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 (10% all Grades; 2.1% Grades 3 or 4) and new or worsening
hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5%
of 210 patients with cHL, and treatment was interrupted due to adverse
reactions in 26% of patients. Fifteen percent (15%) of patients had an
adverse reaction requiring systemic corticosteroid therapy. Serious
adverse reactions occurred in 16% of patients. The most frequent serious
adverse reactions (≥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 (occurring
in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%),
musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in
11% of 370 patients with locally advanced or metastatic urothelial
carcinoma. The most common adverse reactions (in ≥20% of patients) were
fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%),
constipation (21%), rash (21%), and diarrhea (20%). Eighteen patients
(5%) died from causes other than disease progression. Five patients
(1.4%) who were treated with KEYTRUDA experienced sepsis which led to
death, and 3 patients (0.8%) experienced pneumonia which led to death.
Adverse reactions leading to interruption of KEYTRUDA occurred in 22% of
patients; the most common (≥1%) were liver enzyme increase, diarrhea,
urinary tract infection, acute kidney injury, fatigue, joint pain, and
pneumonia. Serious adverse reactions occurred in 42% of patients, the
most frequent (≥2%) of which were urinary tract infection, hematuria,
acute kidney injury, pneumonia, and urosepsis.

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%). Adverse reactions
leading to interruption of KEYTRUDA occurred in 20% of patients; the
most common (≥1%) were urinary tract infection (1.5%), diarrhea (1.5%),
and colitis (1.1%). The most common adverse reactions (≥20%) in patients
who received KEYTRUDA vs those who received chemotherapy were fatigue
(38% vs 56%), musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%),
decreased appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs
13%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated
patients, the most frequent (≥2%) of which were urinary tract infection,
pneumonia, anemia, and pneumonitis.

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.

There is limited experience in pediatric patients. In a study, 40
pediatric patients (16 children aged 2 years to younger than 12 years
and 24 adolescents aged 12 years to 18 years) with advanced melanoma,
lymphoma, or PD-L1–positive advanced, relapsed, or refractory solid
tumors were administered KEYTRUDA 2 mg/kg every 3 weeks. Patients
received KEYTRUDA for a median of 3 doses (range 1–17 doses), with 34
patients (85%) receiving KEYTRUDA for 2 doses or more. The safety
profile in these pediatric patients 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%).

About Lynparza® (olaparib) tablets, 150mg

Lynparza is a first-in-class poly ADP-ribose polymerase (PARP)
inhibitor and the first targeted treatment to potentially exploit tumor
DNA damage response (DDR)-pathway deficiencies to preferentially kill
cancer cells. Specifically, in vitro studies have shown that
Lynparza-induced cytotoxicity may involve inhibition of PARP enzymatic
activity and increased formation of PARP-DNA complexes, resulting in DNA
damage and cancer cell death.

Indications for Lynparza in the U.S.

Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

For the maintenance treatment of adult patients with recurrent
epithelial ovarian, fallopian tube, or primary peritoneal cancer, who
are in complete or partial response to platinum-based chemotherapy.

For the treatment of adult patients with deleterious or suspected
deleterious germline BRCA-mutated (gBRCAm) advanced
ovarian cancer who have been treated with 3 or more prior lines of
chemotherapy. Select patients for therapy based on an FDA-approved
companion diagnostic for Lynparza.

In patients with deleterious or suspected deleterious gBRCAm, human
epidermal growth factor receptor 2 (HER2)-negative metastatic breast
cancer who have previously been treated with chemotherapy in the
neoadjuvant, adjuvant or metastatic setting. Patients with hormone
receptor (HR)-positive breast cancer should have been treated with a
prior endocrine therapy or be considered inappropriate for endocrine
treatment. Select patients for therapy based on an FDA-approved
companion diagnostic for Lynparza.

Important Safety Information for Lynparza

Contraindications

There are no contraindications for Lynparza.

Warnings and Precautions

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred
in <1.5% of patients exposed to Lynparza monotherapy, and the majority
of events had a fatal outcome. The duration of therapy in patients who
developed secondary MDS/AML varied from <6 months to >2 years. All of
these patients had previous chemotherapy with platinum agents and/or
other DNA-damaging agents, including radiotherapy, and some also had a
history of more than one primary malignancy or of bone marrow dysplasia.

Do not start Lynparza until patients have recovered from hematological
toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete
blood count for cytopenia at baseline and monthly thereafter for
clinically significant changes during treatment. For prolonged
hematological toxicities, interrupt Lynparza and monitor blood count
weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer
the patient to a hematologist for further investigations, including bone
marrow analysis and blood sample for cytogenetics. Discontinue Lynparza
(olaparib) if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to Lynparza, and
some cases were fatal. If patients present with new or worsening
respiratory symptoms such as dyspnea, cough, and fever, or a
radiological abnormality occurs, interrupt Lynparza treatment and
initiate prompt investigation. Discontinue Lynparza if pneumonitis is
confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and
findings in animals, Lynparza can cause fetal harm. A pregnancy test is
recommended for females of reproductive potential prior to initiating
treatment.

Females

Advise females of reproductive potential of the potential risk to a
fetus and to use effective contraception during treatment and for 6
months following the last dose.

Males

Advise male patients with female partners of reproductive potential or
who are pregnant to use effective contraception during treatment and for
3 months following the last dose of Lynparza and to not donate sperm
during this time.

Adverse Reactions—Maintenance Setting

Most common adverse reactions (Grades 1-4) in ≥20% of patients in
clinical trials of Lynparza in the maintenance setting for SOLO-2:
nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting
(37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza
(36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%),
headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%),
vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract
infection (22%), constipation (22%), headache (21%), and decreased
appetite (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in
clinical trials of Lynparza in the maintenance setting (SOLO-2/Study
19
) were: increase in mean corpuscular volume (89%/82%), decrease in
hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in
lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%),
increase in serum creatinine (44%/45%), and decrease in platelets
(42%/36%).

Adverse Reactions—Advanced gBRCAm Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in
clinical trials of Lynparza for advanced gBRCAm ovarian cancer
after 3 or more lines of chemotherapy
(pooled from 6 studies) were:
fatigue (including asthenia) (66%), nausea (64%), vomiting (43%), anemia
(34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection
(URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%),
and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in
clinical trials of Lynparza for advanced gBRCAm ovarian cancer (pooled
from 6 studies) were: decrease in hemoglobin (90%), increase in mean
corpuscular volume (57%), decrease in lymphocytes (56%), increase in
serum creatinine (30%), decrease in platelets (30%), and decrease in
absolute neutrophil count (25%).

Adverse Reactions—gBRCAm, HER2-Negative Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in OlympiAD
were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%),
vomiting (30%), neutropenia (27%), respiratory tract infection (27%),
leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in OlympiAD
were: decrease in hemoglobin (82%), decrease in lymphocytes (73%),
decrease in leukocytes (71%), increase in mean corpuscular volume (71%),
decrease in absolute neutrophil count (46%), and decrease in platelets
(33%).

Drug Interactions

Anticancer Agents: Clinical studies of Lynparza in combination
with other myelosuppressive anticancer agents, including DNA-damaging
agents, indicate a potentiation and prolongation of myelosuppressive
toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate
CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be
co-administered, reduce the dose of Lynparza. Advise patients to avoid
grapefruit, grapefruit juice, Seville oranges, and Seville orange juice
during Lynparza treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A
inducers when using Lynparza (olaparib). If a moderate inducer cannot be
avoided, there is a potential for decreased efficacy of Lynparza.

Use in Specific Populations

Lactation: No data are available regarding the presence of
olaparib in human milk, its effects on the breastfed infant or on milk
production. Because of the potential for serious adverse reactions in
the breastfed infant, advise a lactating woman not to breastfeed during
treatment with Lynparza and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of Lynparza have not been
established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is
required in patients with mild hepatic impairment (Child-Pugh
classification A). There are no data in patients with moderate or severe
hepatic impairment.

Renal Impairment: No adjustment to the starting dose is necessary
in patients with mild renal impairment (CLcr=51-80 mL/min). In patients
with moderate renal impairment (CLcr=31-50 mL/min), reduce the dose to
200 mg twice daily. There are no data in patients with severe renal
impairment or end-stage renal disease (CLcr ≤30 mL/min).

Dosing and Administration

To avoid substitution errors and overdose, do not substitute Lynparza
tablets with Lynparza capsules on a milligram-to-milligram basis
due to differences in the dosing and bioavailability of each
formulation. Recommended tablet dose is 300 mg, taken orally twice
daily, with or without food. Continue treatment until disease
progression or unacceptable toxicity. For adverse reactions, consider
dose interruption or dose reduction.

About LENVIMA® (lenvatinib)

LENVIMA® (lenvatinib) is a kinase inhibitor that is indicated
for:

  • Differentiated Thyroid Cancer (DTC): single agent for patients with
    locally recurrent or metastatic, progressive, radioactive
    iodine-refractory DTC.
  • Renal Cell Cancer (RCC): in combination with everolimus for patients
    with advanced RCC following one prior anti-angiogenic therapy.

Lenvatinib, discovered and developed by Eisai, is a receptor tyrosine
kinase (RTK) inhibitor that inhibits the kinase activities of vascular
endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR),
and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been
implicated in pathogenic angiogenesis, tumor growth, and cancer
progression in addition to their normal cellular functions, including
fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived
growth factor receptor alpha (PDGFRα), KIT, and RET

Important Safety Information

Warnings and Precautions

  • In DTC, hypertension was reported in 73% of patients on LENVIMA vs 16%
    with placebo (44% vs 4% grade ≥3). In RCC, hypertension was reported
    in 42% of patients on LENVIMA + everolimus vs 10% with everolimus
    alone (13% vs 2% grade 3). Serious complications of poorly controlled
    hypertension, including aortic dissection, have been reported.
    Systolic blood pressure ≥160 mmHg occurred in 29% of patients, and 21%
    of patients had a diastolic blood pressure ≥100 mmHg in the LENVIMA +
    everolimus–treated group. Blood pressure should be controlled prior to
    treatment and monitored throughout. Withhold dose for grade 3
    hypertension despite optimal antihypertensive therapy; resume at
    reduced dose when controlled at grade ≤2. Discontinue for
    life-threatening hypertension
  • In DTC, cardiac dysfunction was reported in 7% of patients on LENVIMA
    vs 2% with placebo (2% vs 0% grade ≥3). In RCC, decreased ejection
    fraction and cardiac failure were reported in 10% of patients on
    LENVIMA + everolimus vs 6% with everolimus alone (3% vs 2% grade 3).
    Monitor for signs/symptoms of cardiac decompensation. Withhold LENVIMA
    for development of grade 3 cardiac dysfunction until improvement to
    grade 0, 1, or baseline. Resume at reduced dose or discontinue based
    on severity and persistence of cardiac dysfunction. Discontinue for
    grade 4 cardiac dysfunction
  • In DTC, arterial thromboembolic events were reported in 5% of patients
    on LENVIMA vs 2% with placebo (3% vs 1% grade ≥3). In RCC, arterial
    thromboembolic events were reported in 2% of patients on LENVIMA +
    everolimus vs 6% with everolimus alone (2% vs 4% grade ≥3).
    Discontinue following an arterial thrombotic event. The safety of
    resuming LENVIMA after an arterial thromboembolic event has not been
    established, and LENVIMA has not been studied in patients who have had
    an arterial thromboembolic event within the previous 6 months
  • Across clinical studies in which 1,160 patients received LENVIMA
    monotherapy, hepatic failure (including fatal events) was reported in
    3 patients and acute hepatitis in 1 patient. In DTC, ALT and AST
    increases (grade ≥3) occurred in 4% and 5% of patients on LENVIMA,
    respectively, vs 0% with placebo. In RCC, ALT and AST increases (grade
    ≥3) occurred in 3% of patients on LENVIMA + everolimus vs 2% and 0%
    with everolimus alone, respectively. Monitor liver function before
    initiation, then every 2 weeks for the first 2 months, and at least
    monthly thereafter during treatment. Withhold dose for liver
    impairment grade ≥3 until resolved to grade 0, 1, or baseline. Resume
    at reduced dose or discontinue based on severity/persistence of
    hepatotoxicity. Discontinue for hepatic failure
  • In DTC, proteinuria was reported in 34% of patients on LENVIMA vs 3%
    with placebo (11% vs 0% grade 3). In RCC, proteinuria was reported in
    31% of patients on LENVIMA + everolimus vs 14% with everolimus alone
    (8% vs 2% grade 3). Monitor for proteinuria before and during
    treatment. Withhold dose for proteinuria ≥2 g/24 h. Resume at reduced
    dose when proteinuria is <2 g/24 h. Discontinue for nephrotic syndrome
  • In RCC, diarrhea was reported in 81% of patients on LENVIMA +
    everolimus vs 34% with everolimus alone (19% vs 2% grade ≥3). Initiate
    prompt medical management for the development of diarrhea. Monitor for
    dehydration. Withhold dose for diarrhea grade ≥3. Resume at a reduced
    dose when diarrhea resolves to grade 1 or baseline. Permanently
    discontinue LENVIMA for grade 4 diarrhea despite medical management
  • In DTC, events of renal impairment were reported in 14% of patients on
    LENVIMA vs 2% with placebo (3% vs 1% grade ≥3). In RCC, events of
    renal impairment were reported in 18% of patients on LENVIMA +
    everolimus vs 12% with everolimus alone (10% vs 2% grade ≥3). Withhold
    LENVIMA for grade 3 or 4 renal failure/impairment. Resume at reduced
    dose or discontinue, depending on severity/persistence of renal
    impairment. Active management of diarrhea and any other
    gastrointestinal (GI) symptoms should be initiated for grade 1 events
  • In DTC, events of GI perforation or fistula were reported in 2% of
    patients on LENVIMA vs 0.8% with placebo. In RCC, events of GI
    perforation, abscess, or fistula (grade ≥3) were reported in 2% of
    patients on LENVIMA + everolimus vs 0% with everolimus alone.
    Discontinue in patients who develop GI perforation or life-threatening
    fistula
  • In DTC, QT/QTc interval prolongation was reported in 9% of patients on
    LENVIMA vs 2% with placebo (2% vs 0% >500 ms). In RCC, QTc interval
    increases >60 ms were reported in 11% of patients on LENVIMA +
    everolimus (6% >500 ms) vs 0% with everolimus alone. Monitor
    electrocardiograms in patients with congenital long QT syndrome,
    congestive heart failure, bradyarrhythmias, or patients taking drugs
    known to prolong the QT interval. Monitor and correct electrolyte
    abnormalities in all patients. Withhold dose for QTc interval
    prolongation >500 ms. Resume at reduced dose when QTc prolongation
    resolves to baseline
  • In DTC, hypocalcemia (grade ≥3) was reported in 9% of patients on
    LENVIMA vs 2% with placebo. In RCC, hypocalcemia (grade ≥3) was
    reported in 6% of patients on LENVIMA + everolimus vs 2% with
    everolimus alone. Monitor blood calcium levels at least monthly and
    replace calcium as necessary. Interrupt and adjust LENVIMA as necessary
  • Across clinical studies in which 1,160 patients received LENVIMA
    monotherapy, reversible posterior leukoencephalopathy syndrome (RPLS)
    was reported in 4 patients. Withhold LENVIMA for RPLS until fully
    resolved. Resume at reduced dose or discontinue based on the severity
    and persistence of neurologic symptoms
  • Across clinical studies in which 1,160 patients received LENVIMA
    monotherapy, hemorrhage (grade ≥3) was reported in 2% of patients. In
    DTC, hemorrhagic events occurred in 35% of patients on LENVIMA vs 18%
    with placebo (2% vs 3% grade ≥3). There was 1 fatal intracranial
    hemorrhage case among 16 patients who received LENVIMA and had central
    nervous system metastases at baseline. The most frequently reported
    hemorrhagic event was epistaxis (11% grade 1, 1% grade 2).
    Discontinuation due to hemorrhagic events occurred in 1% of patients
    on LENVIMA. In RCC, hemorrhagic events occurred in 34% of patients on
    LENVIMA + everolimus vs 26% with everolimus alone (8% vs 2% grade ≥3).
    The most frequently reported hemorrhagic event was epistaxis (23% for
    LENVIMA + everolimus vs 24% with everolimus alone). There was 1 fatal
    cerebral hemorrhage case. Discontinuation due to hemorrhagic events
    occurred in 3% of patients on LENVIMA + everolimus. Consider the risk
    of severe or fatal hemorrhage associated with tumor
    invasion/infiltration of major blood vessels (eg, carotid artery).
    Withhold LENVIMA for the development of grade 3 hemorrhage until
    resolved to grade 0 or 1. Resume at reduced dose or discontinue based
    on severity/persistence of hemorrhage. Discontinue for grade 4
    hemorrhage
  • In DTC patients with normal baseline thyroid-stimulating hormone
    (TSH), elevation of TSH level above 0.5 mU/L was observed postbaseline
    in 57% of patients on LENVIMA vs 14% with placebo. In RCC, grade 1 or
    2 hypothyroidism occurred in 24% of patients on LENVIMA + everolimus
    vs 2% with everolimus alone. In RCC patients with normal or low TSH at
    baseline, elevation of TSH was observed postbaseline in 60% of
    patients on LENVIMA + everolimus vs 3% with everolimus alone. Monitor
    thyroid function before initiation of and at least monthly throughout
    treatment. Treat hypothyroidism according to standard medical practice
    to maintain a euthyroid state
  • Impaired wound healing, including fistula formation, has been reported
    in patients receiving LENVIMA. Temporary interruption of LENVIMA
    therapy should be considered in patients undergoing major surgical
    procedures
  • LENVIMA can cause fetal harm when administered to a pregnant woman.
    Advise females of reproductive potential to use effective
    contraception during treatment with LENVIMA and for at least 2 weeks
    following completion of therapy

Adverse Reactions

  • In DTC, the most common adverse reactions (≥30%) observed in
    LENVIMA-treated patients vs placebo-treated patients were hypertension
    (73% vs 16%), fatigue (67% vs 35%), diarrhea (67% vs 17%),
    arthralgia/myalgia (62% vs 28%), decreased appetite (54% vs 18%),
    weight decrease (51% vs 15%), nausea (47% vs 25%), stomatitis (41% vs
    8%), headache (38% vs 11%), vomiting (36% vs 15%), proteinuria (34% vs
    3%), palmar-plantar erythrodysesthesia syndrome (32% vs 1%), abdominal
    pain (31% vs 11%), and dysphonia (31% vs 5%)
  • In DTC, adverse reactions led to dose reductions in 68% of patients
    receiving LENVIMA and in 5% of patients receiving placebo; 18% of
    patients discontinued LENVIMA and 5% discontinued placebo for adverse
    reactions. The most common adverse reactions (≥10%) resulting in dose
    reductions of LENVIMA were hypertension (13%), proteinuria (11%),
    decreased appetite (10%), and diarrhea (10%); the most common adverse
    reactions (≥1%) resulting in discontinuation of LENVIMA were
    hypertension (1%) and asthenia (1%)
  • In RCC, the most common adverse reactions (>30%) observed in patients
    treated with LENVIMA + everolimus vs everolimus alone were diarrhea
    (81% vs 34%), fatigue (73% vs 40%), arthralgia/myalgia (55% vs 32%),
    decreased appetite (53% vs 18%), vomiting (48% vs 12%), nausea (45% vs
    16%), stomatitis/oral inflammation (44% vs 50%),
    hypertension/increased blood pressure (42% vs 10%), peripheral edema
    (42% vs 20%), cough (37% vs 30%), abdominal pain (37% vs 8%),
    dyspnea/exertional dyspnea (35% vs 28%), rash (35% vs 40%), weight
    decreased (34% vs 8%), hemorrhagic events (32% vs 26%), and
    proteinuria/urine protein present (31% vs 14%). The most common
    serious adverse reactions (≥5%) were renal failure (11%), dehydration
    (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting
    (5%), and dyspnea (5%)
  • In RCC, adverse reactions led to dose reductions or interruption in
    89% of patients receiving LENVIMA + everolimus and in 54% of patients
    receiving everolimus alone. The most common adverse reactions (≥5%)
    resulting in dose reductions in the LENVIMA + everolimus–treated group
    were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting
    (6%), nausea (5%), and proteinuria (5%). Treatment discontinuation due
    to an adverse reaction occurred in 29% of patients in the
    LENVIMA + everolimus–treated group and in 12% of patients in the
    everolimus-treated group

Use in Specific Populations

  • Because of the potential for serious adverse reactions in nursing
    infants, advise women to discontinue breastfeeding during treatment
  • LENVIMA may result in reduced fertility in females of reproductive
    potential and may result in damage to male reproductive tissues,
    leading to reduced fertility of unknown duration

For more information about LENVIMA, click here for
the full Prescribing Information.

About the AstraZeneca and Merck Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck (known as MSD outside the United
States and Canada) announced a global strategic oncology collaboration
to co-develop and co-commercialize Lynparza, the world's first PARP
inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for
multiple cancer types. The collaboration is based on increasing evidence
that PARP and MEK inhibitors can be combined with PD-L1/PD-1 inhibitors
for a range of tumor types. Working together, the companies will develop
Lynparza and selumetinib in combination with other potential new
medicines and as a monotherapy. Independently, the companies will
develop Lynparza and selumetinib in combination with their respective
PD-L1 and PD-1 medicines.

About the Eisai and Merck Strategic Collaboration

In March 2018, Eisai and Merck, through an affiliate, entered into a
strategic collaboration for the worldwide co-development and
co-commercialization of LENVIMA® (lenvatinib). Under the
agreement, the companies will jointly develop and commercialize LENVIMA,
both as monotherapy and in combination with Merck's anti-PD-1 therapy
KEYTRUDA® (pembrolizumab). In addition to ongoing
clinical studies of the combination, the companies will jointly initiate
new clinical studies evaluating the combination to support 11 potential
indications in six types of cancer, including bladder cancer endometrial
cancer, hepatocellular carcinoma, head and neck cancer, melanoma and
non-small cell lung cancer, as well as a basket trial targeting six
additional cancer types. The LENVIMA/KEYTRUDA combination is not
approved in any cancer types today.

Merck's Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology
medicines to help people with cancer worldwide. At Merck, helping people
fight cancer is our passion and supporting accessibility to our cancer
medicines is our commitment. Our focus is on pursuing research in
immuno-oncology and we are accelerating every step in the journey – from
lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the fastest-growing development
programs in the industry across more than 30 tumor types. We also
continue to strengthen our immuno-oncology portfolio through strategic
acquisitions and are prioritizing the development of several promising
immunotherapeutic 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 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 TwitterFacebookInstagram,
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 Patient Information/Medication Guide for KEYTRUDA at
http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.

Please see complete Prescribing
Information
for Lynparza, including Patient Information
(Medication Guide).

For more information about Lenvima, click here
for the full Prescribing Information.

View Comments and Join the Discussion!