Eisai Announces Data at ASCO 2018 Annual Meeting Showcasing LENVIMA® (lenvatinib) and KEYTRUDA® (pembrolizumab) Combination Therapy Under Strategic Oncology Collaboration with Merck
Eisai Announces Data at ASCO 2018 Annual Meeting Showcasing LENVIMA® (lenvatinib) and KEYTRUDA® (pembrolizumab) Combination Therapy Under Strategic Oncology Collaboration with Merck
- Data highlights continued investigation of LENVIMA as monotherapy and in combination with Merck's KEYTRUDA across multiple cancer types under global collaboration to co-develop and co-commercialize LENVIMA
- LENVIMA/KEYTRUDA combination has already been granted U.S. FDA Breakthrough Therapy Designation for renal cell carcinoma (RCC) with updated results to be presented at ASCO
WOODCLIFF LAKE, N.J., May 17, 2018 /PRNewswire/ -- Eisai Inc. today announced the presentation of new data and analyses at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting from June 1-5 in Chicago. The data to be presented include five abstracts on combination studies of lenvatinib (marketed as LENVIMA(®)), an orally available kinase inhibitor discovered by Eisai, in combination with Merck's anti-PD-1 therapy, pembrolizumab (marketed as KEYTRUDA(®)), in four different tumor types: unresectable hepatocellular carcinoma (Abstract #4076), advanced endometrial carcinoma (Abstract #5596 and Abstract #5597), squamous cell carcinoma of the head and neck (Abstract #6016) and renal cell carcinoma (Abstract #4560).
"This year's ASCO annual meeting marks the first time Eisai and Merck will share exciting developments from combination studies of lenvatinib and pembrolizumab under our new collaboration," said Alton Kremer, MD, PhD, Chief Clinical Officer and Chief Medical Officer, Oncology Business Group at Eisai. "Our data at ASCO include early insights into the potential of lenvatinib and of the lenvatinib+pembrolizumab combination across a variety of difficult-to-treat cancers with limited therapeutic options. Given the clinical activity observed with lenvatinib and when it is combined with pembrolizumab, we have great hope that this is just the start of how this collaboration may begin to provide more options for patients in need."
This release discusses investigational uses for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval.
The full list of Eisai presentations along with the time and location of each session is included below.
Abstract Name Session (All times are Central)
------------- ------------------------------
A phase 1b trial of lenvatinib
(LEN) plus pembrolizumab (PEM)
in patients (pts) with
unresectable hepatocellular
carcinoma (uHCC) Abstract #4076 / Poster Board #265
Poster presentation
Sunday, June 3, 2018
8:00 a.m. - 11:30 a.m.
Location: Hall A
Masafumi Ikeda, MD
--- ------------------
Lenvatinib + Pembrolizumab in
Patients With Advanced
Endometrial Cancer: Updated
Results Abstract #5596 / Poster Board #323
Poster presentation
Monday, June 4, 2018
1:15 p.m. - 4:45 p.m.
Location: Hall A
Vicky Makker, MD
--- ----------------
A phase 1b/2 trial of lenvatinib
plus pembrolizumab in patients
with squamous cell carcinoma of
the head and neck Abstract #6016 / Poster Board #4
Poster discussion session
Saturday, June 2, 2018
4:45 p.m. - 6:00 p.m.
Location: S100a
Poster presentation
Saturday, June 2, 2018
1:15 p.m. - 4:45 p.m.
Location: Hall A
Matthew Taylor, MD
--- ------------------
Lenvatinib + pembrolizumab in
patients with renal cell
carcinoma: updated results Abstract #4560 / Poster Board #386
Poster presentation
Saturday, June 2, 2018
8:00 a.m. - 11:30 a.m.
Location: Hall A
Chung-Han Lee, MD, PhD
--- ----------------------
Biomarker results and preclinical
rationale for combination
lenvatinib and pembrolizumab in
advanced endometrial carcinoma Abstract #5597 / Poster Board #324
Poster presentation
Monday, June 4, 2018
1:15 p.m. - 4:45 p.m.
Location: Hall A
Vicky Makker, MD
--- ----------------
Single-agent expansion cohort of
lenvatinib (LEN) and combination
dose-finding cohort of
LEN+etoposide (ETP)+ifosfamide
(IFM) in patients (Pts) aged 2
to <=25 years with relapsed/
refractory osteosarcoma (OS) Abstract #11527 / Poster Board #272
Poster presentation
Saturday, June 2, 2018
8:00 a.m. - 11:30 a.m.
Location: Hall A
Nathalie Gaspar, MD, PhD
--- ------------------------
Understanding Quality Of Life In
Hepatocellular Carcinoma
Patients Abstract #4093 / Poster Board #282
Poster presentation
Sunday, June 3, 2018
8:00 a.m. - 11:30 a.m.
Location: Hall A
Stacie Hudgens, MA
--- ------------------
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.
LENVIMA, 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). LENVIMA 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 (PDGFR ), KIT, and RET.
Important Safety Information
Warnings and Precautions
-- In DTC, hypertension was reported in 73% of patients on LENVIMA
(lenvatinib) 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 (lenvatinib) + 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 (lenvatinib) 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 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 LENVIMA/KEYTRUDA to support 11 potential indications in six types of cancer (endometrial cancer, non-small cell lung cancer, hepatocellular carcinoma, head and neck cancer, bladder cancer and melanoma), as well as a basket trial targeting six additional cancer types. The LENVIMA/KEYTRUDA combination is not approved in any cancer types today.
About Eisai Inc.
At Eisai Inc., human health care (hhc) is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.
Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Each group functions as an end-to-end global business with discovery, development, manufacturing and marketing capabilities. Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at eisai.com/us.
CONTACT: Media Inquiries: Michele Randazzo, Eisai Inc., (201) 746-2979; Investor Inquiries: Ivor MacLeod, Eisai Inc., (201) 746-2660
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