生物医药系列产品
数据
资源
版本对比
免费注册
预约演示
免费注册
Eisai
Showcases Oncology Portfolio and Pipeline at ASCO 2024
2024-05-23
·
交易
·
BioSpace
ASCO会议
临床结果
临床3期
临床1期
临床2期
Biomarker Analyses from Pivotal Phase 3 CLEAR Trial in Patients with
Advanced Renal Cell Carcinoma
Will Be Featured in an Oral Presentation Additional Data From
Eisai
's Pipeline Provide Insights Into
Metastatic Breast Cancer
and Other
Solid Tumors
NUTLEY, N.J., May 23, 2024 /PRNewswire/ --
Eisai Inc.
announced today the presentation of research across multiple types of
cancer
from its oncology portfolio and pipeline during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (#ASCO24), which is taking place virtually and in-person in Chicago, Illinois from May 31 to June 4. Notable data include an oral presentation on biomarker analyses from the pivotal Phase 3 CLEAR (Study 307)/KEYNOTE-581 trial (NCT02811861), which evaluated
lenvatinib
(
LENVIMA
®), the orally available multiple receptor tyrosine kinase inhibitor discovered by
Eisai
, plus
pembrolizumab
(
KEYTRUDA
®),
Merck
's anti-
PD-1
therapy, versus
sunitinib
for the first-line treatment of patients with
advanced renal cell carcinoma
(Abstract #4504). An analysis of patterns of disease progression and subsequent therapy from this trial will also be presented in a poster presentation (Abstract #4524). "At
Eisai
, we let the science drive us to new approaches that accelerate progress in oncology, while also remaining grounded in our human health care concept that reinforces our commitment to prioritize the needs of patients and families impacted by a
cancer
diagnosis," said Dr. Takashi Owa, Chief Scientific Officer, Senior Vice President,
Eisai Co., Ltd.
"With this in mind, we look forward to sharing research that provides further insight into the role of
lenvatinib
plus
pembrolizumab
as a first-line standard of care option in
advanced renal cell carcinoma
, as well as research that explores various modalities in our pipeline for the potential treatment of advanced diseases with the goal of improving patients' lives." Other key research of note from
Eisai
's pipeline include an oral presentation of Phase 3 data from the JBCRG-M06/EMERALD study in Japan evaluating
trastuzumab
and
pertuzumab
in combination with
Eisai
's
eribulin mesylate
or a
taxane
in patients with
HER2-positive, locally advanced or metastatic breast cancer
(NCT03264547; Abstract #1007). Additional pipeline research to be presented in poster sessions include an overview of a Phase 2 study of
BB-1701
, an antibody drug conjugate targeting
HER2
, in previously treated patients with HER2-positive or
HER2-low unresectable or metastatic breast cancer
HER2-low
unresectable or metastatic breast cancer (NCT06188559; Abstract #TPS1122), findings from a Phase 1b trial of
tasurgratinib
(development code: E7090) with or without endocrine therapies for patients with
ER
positive,
HER2
negative recurrent/metastatic breast cancer
after receiving a CDK4/6 inhibitor (NCT04572295; Abstract #3103), as well as the dose-expansion part of a Phase 1b global study of E7386 (a Wnt/β-catenin pathway modulator) in combination with lenvatinib in patients with hepatocellular carcinoma and other solid tumors including endometrial cancer (NCT04008797; Abstract #TPS3169). This release discusses investigational compounds and investigational uses for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational compounds or investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval. The full list of
Eisai
presentations is included below. These abstracts will be made available via the ASCO website on Thursday, May 23, 2024, at 5:00 PM EDT. In March 2018,
Eisai
and
Merck
(known as
MSD
outside the United States and Canada), through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of
lenvatinib
, both as monotherapy and in combination with
Merck
's anti-
PD-1
therapy,
pembrolizumab
.
Eisai
and
Merck
are studying the
lenvatinib
plus
pembrolizumab
combination through the LEAP (
LEnvatinib
And
Pembrolizumab
) clinical program in various
tumor
types across multiple clinical trials. In May 2023,
Eisai
entered into a joint development agreement with
Bliss Biopharmaceutical
(Hangzhou) Co., Ltd. (Headquarters: Zhejiang Province, China, "
BlissBio
"), for
BB-1701
, a
HER2-targeting
antibody drug conjugate (ADC), with option rights for a strategic collaboration.
Eisai
and
BlissBio
are currently investigating
BB-1701
in a Phase 2 clinical trial in Japan and the United States for
breast cancer
, and a Phase 1/2 clinical trial in the United States and China for
HER2-expressing solid tumors
HER2-expressing
solid tumors. About BB-1701
BB-1701
is an antibody drug conjugate (ADC) that is composed of
Eisai
's in-house developed cytotoxic agent
eribulin
, and an
anti-HER2 antibody
using a linker, and is expected to have anti-
tumor
effects on
breast, lung and other solid tumors
that express
HER2
through direct cytotoxicity (including immunogenic cell death), a bystander effect* and immune response-induced cell death. *Bystander effect: When the cytotoxic agent and antibody parts of an ADC are separated inside a targeted antigen-positive
cancer
cell, the released cytotoxic agent also affects neighboring antigen-negative cancer cells and the component cells of the
cancer
microenvironment. About
E7386
E7386
is a selective inhibitor of the interaction between the
cAMP response element-binding protein (CREB) binding protein (CBP)
/
β-catenin
and a modulator of the Wnt / β-catenin signaling pathway.
E7386
is thought to block the protein-protein interaction between a transcriptional co-activator, CBP and
β-catenin
, resulting in the inhibition of Wnt / β-catenin pathway-dependent gene expression. Since
E7386
is thought to act on the CBP /
β-catenin
transcription complex located at the most downstream of the
Wnt
signaling, it is expected to inhibit not only ligand-dependent activation but also activation caused by gene mutations in Wnt signaling factors such as adenomatous polyposis coli (APC) and
β-catenin
.
E7386
is created through collaboration research between
Eisai
and
PRISM BioLab Co., Ltd.
(Headquarters: Kanagawa) About
HALAVEN
® (
eribulin mesylate
) Injection (0.5 mg/mL)
HALAVEN
(
eribulin mesylate
) Injection is indicated for the treatment of patients with
metastatic breast cancer (mBC)
who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a
taxane
in either the adjuvant or metastatic setting.
HALAVEN
is also indicated for the treatment of patients with
unresectable or metastatic liposarcoma
who have received a prior anthracycline-containing regimen.
Eribulin
is a
microtubule dynamics inhibitor
in the halichondrin class with a novel mechanism of action, developed in-house by
Eisai
. Structurally,
eribulin
is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai.
Eribulin
is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division. In addition, non-clinical studies showed
eribulin
's unique actions in the
tumor
microenvironment such as an increase in vascular perfusion and permeability in
tumor
cores, promotion of the epithelial state, decrease in capacity of
breast cancer
cells to migrate, etc. Important Safety Information for HALAVEN Warnings and Precautions
Neutropenia
: Severe
neutropenia
(ANC <500/mm3) lasting >1 week occurred in 12% of patients with
mBC
.
Febrile neutropenia
occurred in 5% of patients with
mBC
and 2 patients (0.4%) died from complications. Patients with mBC with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of
Grade 4 neutropenia
and
febrile neutropenia
than patients with normal levels. Monitor complete blood cell counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4
cytopenias
. Delay administration and reduce subsequent doses in patients who experience
febrile neutropenia
or
Grade 4 neutropenia
lasting >7 days.
Peripheral Neuropathy
: Grade 3
peripheral neuropathy
occurred in 8% of patients with
mBC
(Grade 4=0.4%) and 22% developed a new or worsening
neuropathy
that had not recovered within a median follow-up duration of 269 days (range 25-662 days).
Neuropathy
lasting >1 year occurred in 5% of patients with
mBC
. Patients should be monitored for signs of
peripheral motor and sensory neuropathy
. Withhold
HALAVEN
in patients who experience Grade 3 or 4
peripheral neuropathy
until resolution to Grade 2 or less. Embryo-Fetal Toxicity:
HALAVEN
can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with
HALAVEN
and for at least 2 weeks following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with
HALAVEN
and for 3.5 months following the final dose. QT Prolongation: Monitor for prolonged QT intervals in patients with
congestive heart failure
,
bradyarrhythmias
, drugs known to prolong the QT interval, and
electrolyte abnormalities
. Correct
hypokalemia
or
hypomagnesemia
prior to initiating
HALAVEN
and monitor these electrolytes periodically during therapy. Avoid in patients with
congenital long QT syndrome
. Adverse Reactions In patients with
mBC
receiving
HALAVEN
, the most common adverse reactions (≥25%) were
neutropenia
(82%),
anemia
(58%),
asthenia
/
fatigue
(54%),
alopecia
(45%),
peripheral neuropathy
(35%),
nausea
(35%), and
constipation
(25%).
Febrile neutropenia
(4%) and
neutropenia
(2%) were the most common serious adverse reactions. The most common adverse reaction resulting in discontinuation was
peripheral neuropathy
(5%). In patients with
liposarcoma
and
leiomyosarcoma
receiving
HALAVEN
, the most common adverse reactions (≥25%) reported in patients receiving
HALAVEN
were
fatigue
(62%),
nausea
(41%),
alopecia
(35%),
constipation
(32%),
peripheral neuropathy
(29%),
abdominal pain
(29%), and
pyrexia
(28%). The most common (≥5%) Grade 3-4 laboratory abnormalities reported in patients receiving
HALAVEN
were
neutropenia
(32%),
hypokalemia
(5.4%), and
hypocalcemia
(5%).
Neutropenia
(4.9%) and
pyrexia
(4.5%) were the most common serious adverse reactions. The most common adverse reactions resulting in discontinuation were
fatigue
and
thrombocytopenia
(0.9% each). Use in Specific Populations Lactation: Because of the potential for serious adverse reactions in breastfed infants from
eribulin mesylate
, advise women not to breastfeed during treatment with
HALAVEN
and for 2 weeks after the final dose.
Hepatic and Renal Impairment
: A reduction in starting dose is recommended for patients with mild or moderate hepatic impairment and/or moderate or severe
renal impairment
. For more information about
HALAVEN
, click here for the full Prescribing Information.
HALAVEN
® is a registered trademark used by
Eisai Inc.
under license from
Eisai R&D Management Co., Ltd.
About
LENVIMA
® (
lenvatinib
) Capsules
LENVIMA
is indicated: For the treatment of adult patients with locally recurrent or metastatic, progressive, radioactive iodine-
refractory differentiated thyroid cancer (DTC)
In combination with
pembrolizumab
, for the first line treatment of adult patients with
advanced renal cell carcinoma (RCC)
In combination with
everolimus
for the treatment of adult patients with
advanced renal cell carcinoma (RCC)
following one prior anti-angiogenic therapy For the first-line treatment of patients with
unresectable hepatocellular carcinoma (HCC)
In combination with
pembrolizumab
, for the treatment of patients with
advanced endometrial carcinoma (EC)
that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
LENVIMA
, discovered and developed by
Eisai
, is a multiple
receptor tyrosine kinase inhibitor
that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (
FLT1
), VEGFR2 (KDR), and VEGFR3 (FLT4).
LENVIMA
inhibits other kinases 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 (PDGFRA)
,
KIT
, and
RET
.
Lenvatinib
also exhibited antiproliferative activity in
hepatocellular carcinoma
cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2 alpha (FRS2) phosphorylation. In syngeneic mouse
tumor
models, the combination of
lenvatinib
with an
anti-PD-1 monoclonal antibody
decreased
tumor
-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity compared to either treatment alone. The combination of
LENVIMA
and
everolimus
showed increased antiangiogenic and antitumor activity as demonstrated by decreased human endothelial cell proliferation, tube formation, and
VEGF
signaling in vitro and
tumor
volume in mouse xenograft models of human
renal cell cancer
greater than each drug alone. Important Safety Information for LENVIMA Warnings and Precautions
Hypertension
. In DTC (
differentiated thyroid cancer
),
hypertension
occurred in 73% of patients on
LENVIMA
(44% grade 3-4). In
RCC
(
renal cell carcinoma
),
hypertension
occurred in 42% of patients on
LENVIMA
+
everolimus
(13% grade 3). Systolic blood pressure ≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood pressure ≥100 mmHg. In
HCC
(
hepatocellular carcinoma
),
hypertension
occurred in 45% of
LENVIMA
-treated patients (24% grade 3).
Grade 4 hypertension
was not reported in
HCC
. Serious complications of poorly controlled
hypertension
have been reported. Control blood pressure prior to initiation. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at reduced dose when
hypertension
is controlled or permanently discontinue based on severity. Cardiac Dysfunction. Serious and fatal cardiac dysfunction can occur with
LENVIMA
. Across clinical trials in 799 patients with DTC,
RCC
, and
HCC
, grade 3 or higher cardiac dysfunction occurred in 3% of
LENVIMA
-treated patients. Monitor for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity. Arterial Thromboembolic Events. Among patients receiving
LENVIMA
or
LENVIMA
+
everolimus
, arterial thromboembolic events of any severity occurred in 2% of patients in
RCC
and
HCC
and 5% in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials. Among patients receiving
LENVIMA
with
pembrolizumab
,
arterial thrombotic events
of any severity occurred in 5% of patients in CLEAR, including
myocardial infarction
(3.4%) and
cerebrovascular accident
(2.3%). Permanently discontinue following an arterial thrombotic event. The safety of resuming 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. Hepatotoxicity. Across clinical studies enrolling 1327
LENVIMA
-treated patients with
malignancies
other than
HCC
, serious hepatic adverse reactions occurred in 1.4% of patients. Fatal events, including
hepatic failure
,
acute hepatitis
, and
hepatorenal syndrome
, occurred in 0.5% of patients. In
HCC
,
hepatic encephalopathy
occurred in 8% of
LENVIMA
-treated patients (5% grade 3-5). Grade 3-5
hepatic failure
occurred in 3% of
LENVIMA
-treated patients; 2% of patients discontinued
LENVIMA
due to
hepatic encephalopathy
, and 1% discontinued due to
hepatic failure
. Monitor liver function prior to initiation, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with
HCC
closely for signs of
hepatic failure
, including
hepatic encephalopathy
. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.
Renal Failure
or Impairment. Serious including fatal
renal failure
or impairment can occur with
LENVIMA
.
Renal impairment
was reported in 14% and 7% of
LENVIMA
-treated patients in DTC and
HCC
, respectively. Grade 3-5
renal failure
or impairment occurred in 3% of patients with DTC and 2% of patients with
HCC
, including 1 fatal event in each study. In
RCC
,
renal impairment
or
renal failure
was reported in 18% of
LENVIMA
+
everolimus
–treated patients (10% grade 3). Initiate prompt management of
diarrhea
or
dehydration
/
hypovolemia
. Withhold and resume at reduced dose upon recovery or permanently discontinue for
renal failure or impairment
based on severity. Proteinuria. In DTC and
HCC
,
proteinuria
was reported in 34% and 26% of
LENVIMA
-treated patients, respectively.
Grade 3 proteinuria
occurred in 11% and 6% in DTC and
HCC
, respectively. In
RCC
,
proteinuria
occurred in 31% of patients receiving
LENVIMA
+
everolimus
(8% grade 3). Monitor for proteinuria prior to initiation and periodically during treatment. If urine dipstick proteinuria ≥2+ is detected, obtain a 24-hour urine protein. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.
Diarrhea
. Of the 737
LENVIMA
-treated patients in DTC and
HCC
,
diarrhea
occurred in 49% (6% grade 3). In
RCC
,
diarrhea
occurred in 81% of
LENVIMA
+
everolimus
–treated patients (19% grade 3).
Diarrhea
was the most frequent cause of dose interruption/reduction, and
diarrhea
recurred despite dose reduction. Promptly initiate management of
diarrhea
. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity. Fistula Formation and
Gastrointestinal Perforation
. Of the 799 patients treated with
LENVIMA
or
LENVIMA
+
everolimus
in DTC,
RCC
, and
HCC
,
fistula
or
gastrointestinal perforation
occurred in 2%. Permanently discontinue in patients who develop
gastrointestinal perforation
of any severity or grade 3-4 fistula. QT Interval Prolongation. In DTC, QT/QTc interval prolongation occurred in 9% of
LENVIMA
-treated patients and QT interval prolongation of >500 ms occurred in 2%. In
RCC
, QTc interval increases of >60 ms occurred in 11% of patients receiving
LENVIMA
+
everolimus
and QTc interval >500 ms occurred in 6%. In
HCC
, QTc interval increases of >60 ms occurred in 8% of
LENVIMA
-treated patients and QTc interval >500 ms occurred in 2%. Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with
congenital long QT syndrome
,
congestive heart failure
,
bradyarrhythmias
, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at reduced dose upon recovery based on severity. Hypocalcemia. In DTC, grade 3-4
hypocalcemia
occurred in 9% of
LENVIMA
-treated patients. In 65% of cases,
hypocalcemia
improved or resolved following calcium supplementation with or without dose interruption or dose reduction. In
RCC
, grade 3-4
hypocalcemia
occurred in 6% of
LENVIMA
+
everolimus
–treated patients. In
HCC
, grade 3
hypocalcemia
occurred in 0.8% of
LENVIMA
-treated patients. Monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
. Across clinical studies of 1823 patients who received
LENVIMA
as a single agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity and persistence of neurologic symptoms. Hemorrhagic Events. Serious including fatal hemorrhagic events can occur with
LENVIMA
. In DTC,
RCC
, and
HCC
clinical trials, hemorrhagic events, of any grade, occurred in 29% of the 799 patients treated with
LENVIMA
as a single agent or in combination with
everolimus
. The most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were
epistaxis
and
hematuria
. In DTC,
grade 3-5 hemorrhage
occurred in 2% of
LENVIMA
-treated patients, including 1 fatal
intracranial hemorrhage
among 16 patients who received
LENVIMA
and had
CNS metastases
at baseline. In
RCC
,
grade 3-5 hemorrhage
occurred in 8% of
LENVIMA
+
everolimus
–treated patients, including 1 fatal
cerebral hemorrhage
. In
HCC
,
grade 3-5 hemorrhage
occurred in 5% of
LENVIMA
-treated patients, including 7 fatal hemorrhagic events. Serious
tumor
-related bleeds, including fatal hemorrhagic events, occurred in
LENVIMA
-treated patients in clinical trials and in the postmarketing setting. In postmarketing surveillance, serious and fatal
carotid artery hemorrhages
were seen more frequently in patients with
anaplastic thyroid carcinoma (ATC)
than other
tumors
. Safety and effectiveness of
LENVIMA
in patients with
ATC
have not been demonstrated in clinical trials. Consider the risk of severe or fatal
hemorrhage
associated with
tumor
invasion or infiltration of major blood vessels (eg, carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity. Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction.
LENVIMA
impairs exogenous thyroid suppression. In DTC, 88% of patients had baseline thyroid stimulating hormone (TSH) level ≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH level >0.5 mU/L was observed post baseline in 57% of
LENVIMA
-treated patients. In
RCC
and
HCC
, grade 1 or 2 hypothyroidism occurred in 24% of
LENVIMA
+
everolimus
–treated patients and 21% of
LENVIMA
-treated patients, respectively. In patients with normal or low TSH at baseline, elevation of TSH was observed post baseline in 70% of
LENVIMA
-treated patients in
HCC
and 60% of
LENVIMA
+
everolimus
–treated patients in
RCC
. Monitor thyroid function prior to initiation and at least monthly during treatment. Treat
hypothyroidism
according to standard medical practice. Impaired Wound Healing. Impaired wound healing has been reported in patients who received
LENVIMA
. Withhold
LENVIMA
for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of
LENVIMA
after resolution of wound healing complications has not been established.
Osteonecrosis of the Jaw (ONJ)
. ONJ has been reported in patients receiving
LENVIMA
. Concomitant exposure to other risk factors, such as bisphosphonates,
denosumab
,
dental disease
, or invasive dental procedures, may increase the risk of ONJ. Perform an oral examination prior to treatment with
LENVIMA
and periodically during
LENVIMA
treatment. Advise patients regarding good oral hygiene practices and to consider having preventive dentistry performed prior to treatment with
LENVIMA
and throughout treatment with
LENVIMA
. Avoid invasive dental procedures, if possible, while on
LENVIMA
treatment, particularly in patients at higher risk. Withhold
LENVIMA
for at least 1 week prior to scheduled dental surgery or invasive dental procedures, if possible. For patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce the risk of ONJ. Withhold
LENVIMA
if ONJ develops and restart based on clinical judgement of adequate resolution. Embryo-Fetal Toxicity. Based on its mechanism of action and data from animal reproduction studies,
LENVIMA
can cause fetal harm when administered to pregnant women. In animal reproduction studies, oral administration of
lenvatinib
during organogenesis at doses below the recommended clinical doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception during treatment with
LENVIMA
and for 30 days after the last dose. Adverse Reactions In DTC, the most common adverse reactions (≥30%) observed in
LENVIMA
-treated patients were
hypertension
(73%),
fatigue
(67%),
diarrhea
(67%),
arthralgia
/
myalgia
(62%),
decreased appetite
(54%), decreased weight (51%),
nausea
(47%),
stomatitis
(41%),
headache
(38%),
vomiting
(36%),
proteinuria
(34%),
palmar-plantar erythrodysesthesia syndrome
(32%),
abdominal pain
(31%), and dysphonia (31%). The most common serious adverse reactions (≥2%) were
pneumonia
(4%),
hypertension
(3%), and
dehydration
(3%). Adverse reactions led to dose reductions in 68% of
LENVIMA
-treated patients; 18% discontinued
LENVIMA
. The most common adverse reactions (≥10%) resulting in dose reductions 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 (≥20%) observed in
LENVIMA
+
pembrolizumab
-treated patients were
fatigue
(63%),
diarrhea
(62%),
musculoskeletal pain
(58%),
hypothyroidism
(57%),
hypertension
(56%),
stomatitis
(43%),
decreased appetite
(41%),
rash
(37%),
nausea
(36%), decreased weight (30%),
dysphonia
(30%),
proteinuria
(30%), palmar-plantar erythrodysesthesia syndrome (29%), abdominal pain (27%), hemorrhagic events (27%), vomiting (26%), constipation (25%), hepatotoxicity (25%), headache (23%), and acute kidney injury (21%). The most common serious adverse reactions (≥2%) were hemorrhagic events (5%),
diarrhea
(4%),
hypertension
(3%),
myocardial infarction
(3%),
pneumonitis
(3%),
vomiting
(3%),
acute kidney injury
(2%),
adrenal insufficiency
(2%),
dyspnea
(2%), and
pneumonia
(2%). Fatal adverse reactions occurred in 4.3% of patients receiving
LENVIMA
in combination with
pembrolizumab
, including
cardio-respiratory arrest
(0.9%),
sepsis
(0.9%), and one case (0.3%) each of
arrhythmia
,
autoimmune hepatitis
,
dyspnea
, hypertensive crisis, increased blood creatinine,
multiple organ dysfunction syndrome
,
myasthenic syndrome
,
myocarditis
,
nephritis
,
pneumonitis
,
ruptured aneurysm
and
subarachnoid hemorrhage
. Serious adverse reactions occurred in 51% of patients receiving
LENVIMA
and
pembrolizumab
. Serious adverse reactions in ≥2% of patients were hemorrhagic events (5%),
diarrhea
(4%),
hypertension
(3%),
myocardial infarction
(3%),
pneumonitis
(3%),
vomiting
(3%),
acute kidney injury
(2%),
adrenal insufficiency
(2%),
dyspnea
(2%), and
pneumonia
(2%). Permanent discontinuation of
LENVIMA
,
pembrolizumab
, or both due to an adverse reaction occurred in 37% of patients; 26%
LENVIMA
only, 29%
pembrolizumab
only, and 13% both drugs. The most common adverse reactions (≥2%) leading to permanent discontinuation of
LENVIMA
,
pembrolizumab
, or both were
pneumonitis
(3%),
myocardial infarction
(3%), hepatotoxicity (3%),
acute kidney injury
(3%),
rash
(3%), and
diarrhea
(2%). Dose interruptions of
LENVIMA
,
pembrolizumab
, or both due to an adverse reaction occurred in 78% of patients receiving
LENVIMA
in combination with
pembrolizumab
.
LENVIMA
was interrupted in 73% of patients and both drugs were interrupted in 39% of patients.
LENVIMA
was dose reduced in 69% of patients. The most common adverse reactions (≥5%) resulting in dose reduction or interruption of
LENVIMA
were
diarrhea
(26%),
fatigue
(18%),
hypertension
(17%),
proteinuria
(13%),
decreased appetite
(12%),
palmar-plantar erythrodysesthesia
(11%),
nausea
(9%),
stomatitis
(9%),
musculoskeletal pain
(8%),
rash
(8%), increased
lipase
(7%),
abdominal pain
(6%), and
vomiting
(6%), increased ALT (5%), and increased amylase (5%). In
RCC
, the most common adverse reactions (≥30%) observed in
LENVIMA
+
everolimus
–treated patients were
diarrhea
(81%),
fatigue
(73%),
arthralgia
/
myalgia
(55%),
decreased appetite
(53%),
vomiting
(48%),
nausea
(45%),
stomatitis
(44%),
hypertension
(42%),
peripheral edema
(42%),
cough
(37%),
abdominal pain
(37%),
dyspnea
(35%),
rash
(35%), decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%). The most common serious adverse reactions (≥5%) were
renal failure
(11%),
dehydration
(10%),
anemia
(6%),
thrombocytopenia
(5%),
diarrhea
(5%),
vomiting
(5%), and
dyspnea
(5%). Adverse reactions led to dose reductions or interruption in 89% of patients. The most common adverse reactions (≥5%) resulting in dose reductions 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
HCC
, the most common adverse reactions (≥20%) observed in
LENVIMA
-treated patients were
hypertension
(45%),
fatigue
(44%),
diarrhea
(39%),
decreased appetite
(34%),
arthralgia
/
myalgia
(31%), decreased weight (31%),
abdominal pain
(30%),
palmar-plantar erythrodysesthesia syndrome
(27%),
proteinuria
(26%),
dysphonia
(24%), hemorrhagic events (23%),
hypothyroidism
(21%), and
nausea
(20%). The most common serious adverse reactions (≥2%) were
hepatic encephalopathy
(5%),
hepatic failure
(3%),
ascites
(3%), and
decreased appetite
(2%). Adverse reactions led to dose reductions or interruption in 62% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were
fatigue
(9%),
decreased appetite
(8%),
diarrhea
(8%),
proteinuria
(7%),
hypertension
(6%), and
palmar-plantar erythrodysesthesia syndrome
(5%). Treatment discontinuation due to an adverse reaction occurred in 20% of patients. The most common adverse reactions (≥1%) resulting in discontinuation of
LENVIMA
were
fatigue
(1%),
hepatic encephalopathy
(2%),
hyperbilirubinemia
(1%), and
hepatic failure
(1%). In EC, the most common adverse reactions (≥20%) observed in
LENVIMA
and
pembrolizumab
–treated patients were
hypothyroidism
(67%),
hypertension
(67%),
fatigue
(58%),
diarrhea
(55%),
musculoskeletal disorders
(53%),
nausea
(49%),
decreased appetite
(44%),
vomiting
(37%),
stomatitis
(35%), decreased weight (34%),
abdominal pain
(34%),
urinary tract infection
(31%),
proteinuria
(29%),
constipation
(27%),
headache
(26%), hemorrhagic events (25%), palmar‐plantar erythrodysesthesia (23%), dysphonia (22%), and rash (20%). Fatal adverse reactions occurred in 4.7% of those treated with
LENVIMA
and
pembrolizumab
, including 2 cases of
pneumonia
, and 1 case of the following:
acute kidney injury
,
acute myocardial infarction
,
colitis
,
decreased appetite
,
intestinal perforation
,
lower gastrointestinal hemorrhage
,
malignant gastrointestinal obstruction
,
multiple organ dysfunction syndrome
,
myelodysplastic syndrome
,
pulmonary embolism
, and
right ventricular dysfunction
. Serious adverse reactions occurred in 50% of patients receiving
LENVIMA
and
pembrolizumab
. Serious adverse reactions with frequency ≥3% were
hypertension
(4.4%), and
urinary tract infection
(3.2%). Discontinuation of
LENVIMA
due to an adverse reaction occurred in 26% of patients. The most common (≥1%) adverse reactions leading to discontinuation of
LENVIMA
were
hypertension
(2%),
asthenia
(1.8%),
diarrhea
(1.2%),
decreased appetite
(1.2%),
proteinuria
(1.2%), and
vomiting
(1.2%). Dose reductions of
LENVIMA
due to adverse reactions occurred in 67% of patients. The most common (≥5%) adverse reactions resulting in dose reduction of
LENVIMA
were
hypertension
(18%),
diarrhea
(11%),
palmar-plantar erythrodysesthesia syndrome
(9%),
proteinuria
(7%),
fatigue
(7%),
decreased appetite
(6%),
asthenia
(5%), and weight decreased (5%). Dose interruptions of
LENVIMA
due to an adverse reaction occurred in 58% of these patients. The most common (≥2%) adverse reactions leading to interruption of
LENVIMA
were
hypertension
(11%),
diarrhea
(11%),
proteinuria
(6%),
decreased appetite
(5%),
vomiting
(5%), increased alanine aminotransferase (3.5%),
fatigue
(3.5%),
nausea
(3.5%),
abdominal pain
(2.9%), weight decreased (2.6%),
urinary tract infection
(2.6%), increased aspartate aminotransferase (2.3%), asthenia (2.3%), and palmar-plantar erythrodysesthesia (2%). Use in Specific Populations Because of the potential for serious adverse reactions in breastfed children, advise women to discontinue breastfeeding during treatment and for 1 week after the last dose.
LENVIMA
may impair fertility in males and females of reproductive potential. No dose adjustment is recommended for patients with mild (CLcr 60-89 mL/min) or moderate (CLcr 30-59 mL/min)
renal impairment
.
LENVIMA
concentrations may increase in patients with DTC,
RCC
, or EC and severe (CLcr 15-29 mL/min)
renal impairment
. Reduce the dose for patients with DTC,
RCC
, or EC and severe
renal impairment
. There is no recommended dose for patients with
HCC
and severe
renal impairment
.
LENVIMA
has not been studied in patients with
end-stage renal disease
. No dose adjustment is recommended for patients with
HCC
and mild hepatic impairment (Child-Pugh A). There is no recommended dose for patients with
HCC
with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. No dose adjustment is recommended for patients with DTC,
RCC
, or EC and mild or moderate hepatic impairment.
LENVIMA
concentrations may increase in patients with DTC,
RCC
, or EC and severe hepatic impairment. Reduce the dose for patients with DTC,
RCC
, or EC and severe hepatic impairment.
LENVIMA
(
lenvatinib
) is available as 10 mg and 4 mg capsules. Please see Prescribing Information for
LENVIMA
(
lenvatinib
) at About the
Eisai
and
Merck
Strategic Collaboration In March 2018,
Eisai
and
Merck
, known as
MSD
outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of
LENVIMA
. Under the agreement, the companies jointly develop, manufacture and commercialize
LENVIMA
, both as monotherapy and in combination with
Merck
's anti-
PD-1
therapy
KEYTRUDA
.
Eisai
and
Merck
are studying the
KEYTRUDA
plus
LENVIMA
combination through the LEAP (
LEnvatinib
And
Pembrolizumab
) clinical program in various
tumor
types across multiple clinical trials. About
Eisai
Eisai
's Corporate Concept is "to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides." Under this Concept [also known as our human health care (hhc) Concept], we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology. In addition, our continued commitment to the elimination of
neglected tropical diseases (NTDs)
, which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), is demonstrated by our work on various activities together with global partners. For more information about
Eisai
, please visit (for global headquarters:
Eisai Co., Ltd.
), us.eisai.com (for U.S. headquarters:
Eisai Inc.
) or (for Europe, Middle East, Africa, Russia, Australia, and New Zealand headquarters:
Eisai Europe Ltd.
), and connect with us on Twitter (U.S. and global) and LinkedIn (for U.S. and EMEA).
LENVIMA
® is a registered trademark used by
Eisai Inc.
under license from
Eisai R&D Management Co., Ltd.
©2024
Eisai Inc.
All Rights Reserved.
KEYTRUDA
® is a registered trademark of
Merck Sharp & Dohme LLC
, a subsidiary of
Merck & Co., Inc.
, Rahway, N.J., U.S.A.
更多内容,
请访问原始网站
文中所述内容并不反映新药情报库及其所属公司任何意见及观点,如有版权侵扰或错误之处,请及时联系我们,我们会在24小时内配合处理。
机构
Eisai Co., Ltd.
Eisai, Inc.
Merck & Co., Inc.
[+6]
适应症
晚期肾细胞癌
转移性乳腺癌
实体瘤
[+102]
靶点
PD-1
HER2
ER
[+10]
药物
甲磺酸仑伐替尼
帕博利珠单抗
苹果酸舒尼替尼
[+13]
标准版
¥
16800
元/账号/年
新药情报库 | 省钱又好用!
立即使用
来和芽仔聊天吧
热门报告
特应性皮炎深度解析:药物开发、专利分析与风险评估
智慧芽生物医药
2024年7月全球首批及特殊审评药物报告
智慧芽生物医药
GPRC5D靶点专利调研报告
智慧芽生物医药
立即开始免费试用!
智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台,助您全方位提升您的研发与决策效率。
开始免费试用
立即开始数据试用!
智慧芽新药库数据也通过智慧芽数据服务平台,以API或者数据包形式对外开放,助您更加充分利用智慧芽新药情报信息。
试用数据服务