Eisai Delivers New Data ASCO 2023, Highlights Continued Progress of Oncology Portfolio and Pipeline | biospace (2023)

Definitive pre-specified overall survival analysis of the pivotal Phase 3 CLEAR trial in patients withAdvanced renal cell carcinoma will be presented in an oral presentation

NUTLEY, NJ, May 23, 2023 r. /PRNewswire/ --Come ontoday announced the presentation of research on a range of cancers from its oncology portfolio at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting (#ASCO23), which will be held virtually and in person in Chicago, Illinois, June 2-6.

Notable study findings include an oral presentation of the results of the final, pre-specified overall survival analysis of the pivotal phase 3 CLEAR (study 307)/KEYNOTE-581 lenvatinib trial (LENVIMA).^®) plus pembrolizumab (KEYTRUDA^®) compared to sunitinib in the first-line treatment of patients with advanced renal cell carcinoma (Summary No. 4502). A post-hoc analysis of the REFLECT trial evaluating lenvatinib monotherapy versus sorafenib in the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) will also be presented in a poster presentation (Abstract #4078).

"The outlook for advanced renal cell carcinoma has evolved in recent years, and the final analysis of the pivotal CLEAR trial, which will be presented at ASCO, represents further progress for patients and an opportunity to provide long-term data to their physicians," said Dr. Takashi Owa, Chief Scientific Officer, Senior Vice President, Eisai Co., Ltd. "New lenvatinib data from our oncology pipeline demonstrates Eisai's continued commitment to innovation and discovery of new therapies as we strive to achieve our goals."people's healthConcept, our corporate mission to meet the needs of more people facing a cancer diagnosis.

Additional details from Eisai's work include a poster presentation of the results of Phase 1b study E7386, an inhibitor of the CREB-binding protein (CBP)/β-catenin interaction, in combination with lenvatinib in patients with advanced HCC (Excerpt #4075) and a small cohort of lung cancer cells in Phase 1 Study 1b/2 evaluating E7389-LF, a novel liposomal formulation of eribulin, in combination with nivolumab (Extract #8593). Preclinical results of farletuzumab ecteribulin (FZEC), formerly known as MORAb-202 and MORAb-109, antibody-drug conjugates (ADCs), in rare gynecologic cancers are also published online (abstract #e17634).

In addition, Bliss Biopharmaceutical Co., Ltd. (BlissBio) will present a poster at the conference showing the results of the first human study of BB-1701, an ADC targeting HER2 (Abstract No. 3029). Eisai entered into a joint development agreement with BlissBio for BB-1701 in April 2023 with option rights for a strategic partnership. A phase 1/2 clinical trial of BB-1701 for HER2-expressing solid tumors is underway in the US and China.

This press release discusses investigational drugs and research uses of FDA-approved products. It is not the intention to draw conclusions about efficacy and safety. There is no guarantee that investigational or experimental drug use of FDA-approved products will successfully complete clinical development or receive FDA approval.

Below is the full list of speeches. These summaries will be available on Thursday, May 25, 2023 at 5:00 PM EDT.

In March 2018, Eisai and Merck (known as MSD outside the U.S. and Canada), through a subsidiary, entered into a strategic partnership to jointly develop and commercialize lenvatinib globally, both alone and in combination with Merck's antibiotic -PD- 1 therapy. pembrolizumab. Eisai and Merck explore combination of LENVIMA and KEYTRUDA under LEAP (NASTYnwatynibAzdPEmbrolizumab) in different cancers in different clinical trials.

In June 2021, Eisai and Bristol Myers Squibb entered into an exclusive global strategic collaboration agreement to co-develop and co-market farletuzumab ecteribulin (FZEC, formerly known as MORAb-202), a folic acid receptor alpha (FRα) ADC. Eisai and Bristol Myers Squibb are currently investigating FZEC in a number of studies, including: US and European Phase 1/2 clinical trial for solid tumors, including endometrial cancer, US and European Phase 2 clinical trial for non-small cell tumors Lung cancer and clinical trial Phase 2- studies in the US, Europe and Japan for ovarian, peritoneal and fallopian tube cancer.

Via E7386
E7386 is a selective inhibitor of the interaction between the cAMP response element-binding protein (CREB) binding protein (CBP)/β-catenin and modulator of Wnt/β-catenin signaling. E7386 is believed to block the protein-protein interaction between the transcription coactivator, CBP and β-catenin, resulting in inhibition of gene expression dependent on the Wnt/β-catenin pathway. Since E7386 acts on the CBP/β-catenin transcription complex most downstream of Wnt signaling, it is expected to inhibit not only ligand-dependent activation, but also activation mediated by gene mutations in Wnt signaling factors such as inhibition of adenomatous polyposis coli (APC). and β-catenin. E7386 is the result of joint research by Eisai and PRISM BioLab Co., Ltd. (Headquarters: Kanagawa)

Information about E7389-LF
E7389-LF is a novel formulation designed to more efficiently deliver the halichondrin class microtubule dynamics inhibitor, HALAVEN^®(eribulin mesylate) introduced into tumor cells by liposome coating. A phase I clinical trial is currently underway in Japan with selected solid tumours. In addition, it is currently being developed in Japan in collaboration with Ono Pharmaceutical Co., Ltd. conducted a phase 1b/2 clinical trial of the combination therapy of E7389-LF and nivolumab in selected solid tumors.

O farletuzumabie ekteribulinie
Farletuzumab Ecteribulin (FZEC), formerly known as MORAb-202, is Eisai and Bristol Myers Squibb's first antibody-drug conjugate (ADC) consisting of Eisai's patented anti-cancer drug, farletuzumab, a humanized IgG1 monoclonal antibody derived from what is believed to be the folate binding receptor alpha (FRα) and Eisai's patented anti-cancer drug, eribulin, using an enzyme-cleavable linker. Eisai and Bristol Myers Squibb are currently conducting a Phase 1 clinical trial in Japan and a Phase 1/2 clinical trial in the United States of FZEC targeting FRα-positive solid tumors, respectively. It is believed that upon entry of the FZEC into FRa-positive tumor target cells, the linker is enzymatically cleaved, releasing eribulin from the antibody, resulting in its antitumor activity. In addition, in non-clinical studies, FZEC has demonstrated a bystander effect with anticancer activity on FRα-negative cancer cells surrounding FRα-positive cancer cells.

Eribulin Cargo (product name: Halaven) was the first inhibitor of microtubule dynamics of the halichondriin class. Structurally, eribulin is a simplified and synthetically produced version of Halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Its function is to inhibit the growth phase of microtubule dynamics, preventing cell division.

O BB-1701
BB-1701 is an antibody-drug conjugate (ADC) consisting of Eisai's anticancer drug, eribulin, and anti-HER2 antibody via a linker, and is said to have anticancer effects on breast, lung, and other body tumors that express HER2 through direct cytotoxicity ( including immunogenic cell death), bystander effect* and immune-mediated cell death. BlissBio is currently conducting Phase 1 and 2 clinical trials in the US and China in HER2-expressing solid tumors.

* Bystander Effect: When the anticancer agent and ADC antibody portions are separated in an antigen-positive cancer cell, the released anticancer agent also affects adjacent antigen-negative cancer cells and the constituent cells of the cancer microenvironment.

O LENVIMIE^®(lenvatinib) capsules

LENVIMA is indicated:

• For the treatment of patients with locally recurrent or metastatic, progressive, radioiodine-resistant 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 prior anti-angiogenic therapy
• For initial treatment of patients with inoperable hepatocellular carcinoma (HCC)
• In combination with pembrolizumab for the treatment of patients with advanced endometrial cancer (EC) who have remediable linkage errors (pMMR) or are not microsatellite unstable (MSI-H) by an FDA-cleared assay and whose disease has progressed after previous systemic therapy in any setting, not candidates for surgery or radiotherapy.

Discovered and developed by Eisai, LENVIMA is a multi-receptor tyrosine kinase inhibitor that inhibits the kinase activity of the vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases involved in the pathogenesis of angiogenesis, tumor growth and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, platelet-derived growth factor receptor alpha (PDGFRα), and KIT and RET. Lenvatinib also demonstrated antiproliferative activity in hepatocellular carcinoma cell lines mediated by activated FGFR signaling with concomitant inhibition of FGF receptor substrate 2α (FRS2α) phosphorylation. In syngeneic mouse tumor models, the combination of lenvatinib with an anti-PD-1 monoclonal antibody reduced the number of tumor-associated macrophages, increased the number of activated cytotoxic T cells, and showed greater antitumor activity compared to either treatment alone. The combination of LENVIMA and everolimus demonstrated enhanced anti-angiogenic and anti-tumor activity, as evidenced by reduced proliferation of human endothelial cells, reduced tube formation and reduced VEGF signaling in vitro, and greater tumor volume in mouse xenograft models of human renal cell carcinoma than either drug alone.

important safety instructions

Warnings and Measures

Hypertension.In DTC (differentiated thyroid cancer), hypertension occurred in 73% of LENVIMA-treated patients (44% Grade 3-4). In RCC (renal cell carcinoma), hypertension occurred in 42% of patients receiving LENVIMA + everolimus (13% Grade 3). Twenty-nine percent of patients had systolic blood pressure ≥ 160 mmHg 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 has not been reported in HCC.

Serious complications of poorly controlled hypertension have been reported. Check your blood pressure before you start. Check your blood pressure after one week, then every two weeks for the first two months and then at least monthly during treatment. Once the high blood pressure is controlled, treatment should be discontinued and restarted at a reduced dose or permanently discontinued, depending on severity.

dysfunction of the heart.LENVIMA can cause serious and fatal heart problems. In clinical studies of 799 patients with DTC, RCC, and HCC, 3% of patients treated with LENVIMA had Grade 3 or greater cardiac dysfunction. Watch for clinical signs or signs of cardiac dysfunction. Discontinue treatment and resume treatment at a reduced dose upon recovery, or discontinue treatment permanently, depending on severity.

Arterial thromboembolic events.Of patients receiving LENVIMA or LENVIMA + everolimus, arterial thromboembolic events of any grade occurred in 2% of patients in RCC and HCC and 5% of patients in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% in all clinical trials.

Among patients receiving LENVIMA with pembrolizumab, arterial thrombotic events of any grade, including myocardial infarction (3.4%) and cerebrovascular accident (2.3%), occurred in 5% of patients in the CLEAR study.

Permanently discontinue use after arterial thrombosis. The safety of re-treatment after arterial thromboembolism has not been established and LENVIMA has not been studied in patients who had an arterial thromboembolism within the previous 6 months.

hepatotoxicity.In clinical trials of 1,327 patients treated with LENVIMA with malignancies other than HCC, 1.4% of patients experienced serious hepatic adverse reactions. Fatal events, including liver 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% due to hepatic failure.

Liver function should be monitored prior to treatment, then every 2 weeks for the first 2 months and then at least monthly during treatment. Patients with HCC should be carefully monitored for signs of hepatic impairment, including hepatic encephalopathy. Discontinue treatment and resume treatment at a reduced dose upon recovery, or discontinue treatment permanently, depending on severity.

Renal failure or renal impairment.Severe or fatal renal failure or renal impairment may occur during treatment with LENVIMA. Renal dysfunction was reported in 14% and 7% of patients treated with LENVIMA with DTC and HCC, respectively. Grade 3-5 renal failure or impairment, including one fatal event in each study, occurred in 3% of DTC patients and 2% of HCC patients. In RCC, renal dysfunction or renal failure was reported in 18% of patients treated with LENVIMA + everolimus (10% Grade 3).

Treat diarrhea or dehydration/hypovolaemia immediately. Discontinue use and resume treatment at a reduced dose upon recovery, or permanently discontinue treatment in case of renal insufficiency or renal dysfunction, depending on the severity.

proteinuria.For DTC and HCC, proteinuria was reported in 34% and 26% of patients treated with LENVIMA, respectively. Grade 3 proteinuria occurred in 11% and 6% of DTC and HCC patients, respectively. In RCC, proteinuria occurred in 31% of patients receiving LENVIMA + everolimus (8% Grade 3). Proteinuria should be monitored before starting treatment and regularly during treatment. If ≥2+ proteinuria is detected with a urine dipstick test, a 24-hour urine protein test should be performed. Discontinue treatment and resume treatment at a reduced dose upon recovery, or discontinue treatment permanently, depending on severity.

Diarrhea.Of the 737 patients treated with LENVIMA with DTC and HCC, 49% developed diarrhea (6% Grade 3). In RCC, 81% of patients treated with LENVIMA + everolimus experienced diarrhea (19% Grade 3). Diarrhea was the most common reason for dose interruption/reduction, with recurrent diarrhea despite dose reduction. Treat diarrhea immediately. Discontinue treatment and resume treatment at a reduced dose upon recovery, or discontinue treatment permanently, depending on severity.

fistula formation and perforation of the digestive tract.Of the 799 patients treated with LENVIMA or LENVIMA + everolimus for DTC, RCC, and HCC, 2% developed a GI fistula or perforation. Treatment should be permanently discontinued in patients who develop a Grade 3-4 gastrointestinal perforation or Grade 3-4 fistula.

QT prolongation.In the DTC, 9% of LENVIMA-treated patients experienced QT/QTc prolongation and 2% experienced QT prolongation > 500 msec. In renal cell carcinoma, 11% of patients receiving LENVIMA + everolimus had QTc prolongation > 60 msec and 6% of patients receiving QTc > 500 msec. In HCC, 8% of LENVIMA-treated patients had QTc prolongation > 60 msec and 2% > 500 msec.

Monitor and correct electrolyte abnormalities at the start and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, heart failure, bradyarrhythmias, or patients taking drugs that prolong the QT interval, including class Ia and III antiarrhythmics. Discontinue treatment and, upon recovery, resume treatment at reduced dose, depending on severity.

hypocalcemia.In the DTC, grade 3-4 hypocalcaemia occurred in 9% of LENVIMA-treated patients. In 65% of cases, hypocalcaemia improved or resolved with calcium supplementation with or without dose interruption or reduction. In RCC, Grade 3-4 hypocalcaemia occurred in 6% of patients treated with LENVIMA + everolimus. In HCC, Grade 3 hypocalcaemia occurred in 0.8% of LENVIMA-treated patients. Check your blood calcium levels at least once a month and supplement with calcium if necessary during treatment. Discontinue use and resume dose upon recovery or discontinue permanently depending on severity.

Reversible posterior leukoencephalopathy syndrome (RPLS).In clinical trials of 1,823 patients receiving LENVIMA alone, the incidence of RPLS was 0.3%. Confirm the diagnosis of RPLS with an MRI. Depending on the severity and persistence of neurological symptoms, interrupt and resume treatment at a reduced dose or discontinue completely upon recovery.

Hemorrhagic events.Serious bleeding, including fatal, can occur with the use of LENVIMA. In the DTC, RCC and HCC clinical trials, bleeding of any grade occurred in 29% of 799 patients treated with LENVIMA alone or in combination with everolimus. The most commonly reported haemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and haematuria. In the DTC, Grade 3-5 bleeds occurred in 2% of patients treated with LENVIMA, including 1 fatal intracranial bleed in 16 patients receiving LENVIMA who had CNS metastases at baseline. In RCC, grade 3-5 haemorrhage, including 1 fatal cerebral haemorrhage, occurred in 8% of patients treated with LENVIMA + everolimus. In HCC, grade 3-5 bleeding occurred in 5% of LENVIMA-treated patients, including 7 fatal bleeding events. Serious tumor-related bleeding events, including fatal bleeding events, have occurred in patients treated with LENVIMA in clinical trials and post-marketing experience. In post-marketing experience, serious and fatal carotid artery haemorrhages were more frequently observed in patients with anaplastic thyroid carcinoma (ATC) than in other malignancies. The safety and efficacy of LENVIMA in patients with ATC have not been established in clinical trials.

The risk of serious or fatal bleeding associated with tumor invasion or infiltration of major blood vessels (e.g. carotid artery) should be considered. Discontinue treatment and resume treatment at a reduced dose upon recovery, or discontinue treatment permanently, depending on severity.

Decreased thyroid stimulating hormone suppression/thyroid dysfunction.LENVIMA interferes with exogenous thyroid suppression. In the DTC study, 88% of patients had baseline thyroid stimulating hormone (TSH) levels ≤ 0.5 mU/L. In patients with normal baseline TSH levels, 57% of LENVIMA-treated patients had post-baseline elevations in TSH levels > 0.5 mIU/L. In RCC and HCC, Grade 1 or 2 hypothyroidism occurred in 24% of patients treated with LENVIMA + everolimus and 21% of patients treated with LENVIMA, respectively. In patients with normal or low TSH levels at baseline, post-baseline TSH elevations were observed in 70% of HCC patients treated with LENVIMA and 60% of RCC patients treated with LENVIMA + everolimus.

Thyroid function should be checked before starting treatment and at least monthly during treatment. Hypothyroidism should be treated according to standard medical practice.

Decreased wound healing.Impaired wound healing has been reported in patients receiving LENVIMA. Discontinue administration of LENVIMA for at least 1 week before elective surgery. Do not administer for at least 2 weeks after major surgery and until the wound is sufficiently healed. The safety of resuming LENVIMA treatment 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.

An oral examination should be performed prior to treatment with LENVIMA and periodically during treatment with LENVIMA. Patients should be educated on good oral hygiene practices and preventive dental care should be considered prior to and during treatment with LENVIMA.

If possible, invasive dental procedures should be avoided during treatment with LENVIMA, especially in high-risk patients. If possible, you should stop using LENVIMA at least 1 week before a scheduled dental or invasive dental procedure. In patients requiring invasive dental procedures, discontinuation of bisphosphonate therapy may reduce the risk of ONJ.

Discontinue LENVIMA if ONJ develops and resume based on clinical assessment of adequate resolution.

Embryo-Fetal Toxicity.Based on the mechanism of action and data from animal reproduction studies, LENVIMA may cause fetal harm in pregnant women. In animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended clinical dose in rats and rabbits resulted in embryotoxicity, foetotoxicity and teratogenicity. Pregnant women should be advised of the potential risk to the fetus and women of childbearing potential to use effective contraception during treatment with LENVIMA and for 30 days after the last dose.

side effects
For 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 %). %)). %), weight decreased (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 events resulted in dose reductions in 68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most common adverse reactions (≥10%) leading to dose reduction were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); The most common adverse reactions (≥1%) leading to discontinuation of LENVIMA were hypertension (1%) and asthenia (1%).

In the RCC, the most common adverse reactions (≥20%) observed in patients treated with LENVIMA + pembrolizumab were fatigue (63%), diarrhea (62%), musculoskeletal pain (58%), hypothyroidism (57%), hypertension (56%) %). ). %), stomatitis (43%), decreased appetite (41%), rash (37%), nausea (36%), weight decreased (30%), dysphonia (30%), proteinuria (30%), hand-foot syndrome erythrodysaesthesia syndrome (29%), abdominal pain (27%), bleeding (27%), vomiting (26%), constipation (25%), hepatotoxicity (25%), headache (23%), and acute kidney injury (21%). % . The most common serious adverse reactions (≥2%) were bleeding (5%), diarrhea (4%), hypertension (3%), myocardial infarction (3%), pneumonia (3%), vomiting (3%), acute renal failure ( 2%), adrenal insufficiency (2%), shortness of breath (2%), and pneumonia (2%). Fatal adverse events, including cardiac arrest (0.9%), sepsis (0.9%), and one case each (0.3%) of arrhythmias, autoimmune hepatitis, dyspnea and hypertensive crisis, blood creatinine increased, multi-organ dysfunction syndrome, myasthenic syndrome , myocarditis, nephritis, pneumonia, ruptured aneurysm and subarachnoid hemorrhage. Serious adverse reactions occurred in 51% of patients receiving LENVIMA and pembrolizumab. Serious adverse reactions occurring in ≥2% of patients were bleeding (5%), diarrhea (4%), hypertension (3%), myocardial infarction (3%), pneumonia (3%), vomiting (3%), acute trauma (2%), adrenal insufficiency (2%), shortness of breath (2%), and pneumonia (2%). 37% of patients permanently discontinued LENVIMA, pembrolizumab, or both due to an adverse reaction; 26% LENVIMA alone, 29% pembrolizumab alone, and 13% both drugs. The most common adverse reactions (≥2%) leading to permanent discontinuation of LENVIMA, pembrolizumab, or both were pneumonia (3%), myocardial infarction (3%), hepatotoxicity (3%), acute kidney injury (3%), and rash (3%) ) and diarrhea (2%). 78% of patients receiving LENVIMA in combination with pembrolizumab experienced interruptions in LENVIMA, pembrolizumab, or both due to an adverse reaction. 73% of patients discontinued LENVIMA and 39% of patients discontinued both drugs. The dose of LENVIMA was reduced in 69% of patients. The most common adverse reactions (≥5%) leading to dose reduction or discontinuation of LENVIMA were: diarrhea (26%), fatigue (18%), hypertension (17%), proteinuria (13%), decreased appetite (12%) erythrodysaesthesia hand-plantar (11%), nausea (9%), stomatitis (9%), musculoskeletal pain (8%), rash (8%), lipase increased (7%), abdominal pain (6%), and vomiting (6% ), increased ALT (5%) and increased amylase (5%).

In the RCC, the most common adverse reactions (≥30%) observed in patients treated with LENVIMA + everolimus 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%), dyspnoea (35%) , rash (35%), weight loss (34%), bleeding (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%). Dyspnea (5%). Adverse reactions led to dose reduction or discontinuation in 89% of patients. The most common adverse reactions (≥5%) leading to dose reduction were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%) and proteinuria (5%). . ). Discontinuation of treatment 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 %). ). . %), weight decreased (31%), abdominal pain (30%), palmar-plantar erythrodysaesthesia syndrome (27%), proteinuria (26%), dysphonia (24%), hemorrhage (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 reduction or discontinuation in 62% of patients. The most common adverse reactions (≥ 5%) leading to dose reduction were fatigue (9%), decreased appetite (8%), diarrhea (8%), proteinuria (7%), hypertension (6%), and hand-foot discomfort. Erythrodysaesthesia syndrome (5%). Discontinuation of treatment due to an adverse reaction occurred in 20% of patients. The most common adverse reactions (≥1%) leading to discontinuation of LENVIMA were fatigue (1%), hepatic encephalopathy (2%), hyperbilirubinaemia (1%), and hepatic failure (1%).

In EC countries, the most common adverse reactions (≥20%) observed in patients treated with LENVIMA and pembrolizumab were hypothyroidism (67%), hypertension (67%), fatigue (58%), diarrhea (55%), musculoskeletal disorders (53). %), nausea (49%), decreased appetite (44%), vomiting (37%), stomatitis (35%), weight loss (34%), abdominal pain (34%), urinary tract infection (31%) %), proteinuria ( 29%), constipation (27%), headache (26%), bleeding (25%), palmar-plantar erythrodysaesthesia (23%), dysphonia (22%), and rash (20%). Fatal adverse events occurred in 4.7% of patients 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, abdominal bleeding Gastro -Intestinal Cancer, Gastrointestinal Cancer - Disease 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 an incidence of ≥3% were hypertension (4.4%) and urinary tract infection (3.2%). 26% of patients discontinued LENVIMA treatment due to an adverse reaction. The most common adverse reactions (≥1%) leading to discontinuation of LENVIMA were hypertension (2%), asthenia (1.8%), diarrhea (1.2%), decreased appetite (1.2%), proteinuria (1 .2%), 2%). and vomiting (1.2%). %). In 67% of patients, the dose of LENVIMA was reduced due to side effects. The most common adverse reactions (≥5%) leading to dose reduction of LENVIMA were hypertension (18%), diarrhea (11%), palmar-plantar erythrodysaesthesia syndrome (9%), proteinuria (7%), and fatigue (7%). . decreased appetite (6%), asthenia (5%) and weight loss (5%). Dose interruptions of LENVIMA due to an adverse reaction occurred in 58% of these patients. The most common adverse reactions (≥2%) leading to LENVIMA treatment discontinuation were hypertension (11%), diarrhea (11%), proteinuria (6%), decreased appetite (5%), vomiting (5%), alanine aminotransferase increased (3.5%), fatigue (3.5%), nausea (3.5%), abdominal pain (2.9%), weight loss (2.6%), urinary tract infection (2.6%), increased aspartate aminotransferase (2.3%), weakness (2.3). %) and palmar-plantar erythrodysaesthesia (2%).

Use in specific populations
Since serious side effects can occur in breastfed babies, we recommend that women stop breastfeeding during treatment and for one week after the last dose. LENVIMA may impair fertility in men and women of childbearing potential.

No dose adjustment is recommended in patients with mild (CLcr 60-89 ml/min) or moderate (CLcr 30-59 ml/min) renal impairment. LENVIMA levels may be elevated in patients with DTC, RCC or EC and severe renal impairment (CLcr 15-29 ml/min). Reduce the dose in 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 in HCC patients with mild hepatic impairment (Child-Pugh A). There is no recommended dose for HCC patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. No dose adjustment is recommended in patients with DTC, RCC or EC and mild or moderate hepatic impairment. LENVIMA levels may be elevated in patients with DTC, RCC or EC and severe hepatic impairment. Reduce the dose in patients with DTC, RCC or EC and severe hepatic impairment.

LENVIMA (lenvatinib) is available in 10 mg and 4 mg capsules.

See prescribing information for LENVIMA (lenvatinib) below.http://www.lenvima.com/pdfs/precribing-information.pdf.

About the strategic partnership between Eisai and Merck
In March 2018, Eisai and Merck, known outside the United States and Canada as MSD, entered into a strategic partnership through a subsidiary to jointly develop and commercialize LENVIMA globally. Under the terms of the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA alone or in combination with Merck's anti-PD-1 therapy KEYTRUDA.

In addition to ongoing clinical trials of the combination of LENVIMA and KEYTRUDA in a variety of cancers, the companies have jointly initiated new clinical trials under LEAP (NASTYnwatynibAzdPThe "Embrolizumab" clinical program is investigating the combination in several cancer types in several clinical trials.

Eisai
Eisai's business concept is "putting patients and people first in their daily lives and increasing the benefits of healthcare". According to this concept [also known as ourpeople's health(hhk) Concept], we strive to achieve social well-being effectively by alleviating health problems and reducing health inequalities. With a global network of research and development centers, manufacturing facilities and marketing offices, we strive to develop and deliver innovative products to treat diseases with unmet medical needs, with a focus on our strategic areas of neurology and oncology.

Additionally,our continued commitment to eradicating neglected tropical diseases (NTDs),This is the goal (3.3) of the Sustainable Development Goals (SDGs) of the United Nations., is reflected in our work on various activities together with global partners.

For more information on Eisai, seewww.eisai.com(for Global Headquarters: Eisai Co., Ltd.),us.eisai.com(for US headquarters: Eisai Inc.) orwww.eisai.eu(Headquarters for Europe, Middle East, Africa, Russia, Australia and New Zealand: Eisai Europe Ltd.) and connect with us on Twitter (NAS.Iglobal) ILinkedin(DoingNAS.IEMEA).

HIS^®is a registered trademark of Eisai Inc. under license from Eisai R&D Management Co., Ltd. It's being used.

KEYTRUDA^®is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, N.J., USA.

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