Delving into the Latest Updates on Eribulin mesylate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

eribulin, Eribulin Mesilate, Eribulin mesilate (JAN)

+ [17]

Target

Tubulin

Mechanism

Tubulin inhibitors, Tubulin polymerisation inhibitors

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesOther Diseases+ [2]

Active Indication

SarcomaSoft Tissue NeoplasmsBreast Cancer+ [17]

Inactive Indication

Adenocarcinoma of prostateAdvanced breast cancerAdvanced Lung Non-Small Cell Carcinoma+ [47]

Originator Organization

Japan Agency for Medical Research & Development

Active Organization

+ [10]

Inactive Organization

University of Texas Health Science Center At San Antonio

Drug Highest PhaseApproved

First Approval Date

US (15 Nov 2010),

Metastatic breast cancer

RegulationOrphan Drug (US), Orphan Drug (JP)

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Structure

Molecular FormulaC41H63NO14S

InChIKeyQAMYWGZHLCQOOJ-WRNBYXCMSA-N

CAS Registry441045-17-6

A Phase 3, Randomized, Open-label, Multicenter, Controlled Study to Evaluate the Efficacy and Safety of Zanidatamab in Combination With Physician's Choice Chemotherapy Compared to Trastuzumab in Combination With Physician's Choice Chemotherapy for the Treatment of Participants With Metastatic HER2-positive Breast Cancer Who Have Progressed on, or Are Intolerant to, Previous Trastuzumab Deruxtecan Treatment

The efficacy and safety of zanidatamab in combination with physician's choice of chemotherapy compared with trastuzumab in combination with physician's choice of chemotherapy will be evaluated for the treatment of participants with metastatic HER2-positive breast cancer who have progressed on, or are intolerant to, previous T-DXd treatment.

Start Date16 Jul 2024

Sponsor / Collaborator

Jazz Pharmaceuticals Plc

NCT06387628 / RecruitingPhase 2IIT

A Phase II Single Center Two Cohorts Trial of LM-108 in Combination With PD-1 Based Treatment for Patients With Recurrent or Metastatic Triple - Negative Breast Cancer

To evaluate the efficacy and safety of LM108 plus toripalimab plusnab-paclitaxel or eribulin as first-line or post-line treatment in patients with metastatic triple-negative breast cancer.

Start Date01 Jun 2024

Sponsor / Collaborator

Fudan University

NCT06328738 / RecruitingPhase 1

A Phase 1a/1b Study of ELVN-002 Combined With Trastuzumab in Advanced Stage HER2+ Solid Tumors, and ELVN-002 Combined With Trastuzumab and Chemotherapy in Advanced Stage HER2+ Colorectal Cancer and Breast Cancer

The purpose of this study is to determine the safety, tolerability, and recommended dose of ELVN-002 in combination with trastuzumab in participants with advanced-stage HER2-positive tumors and in combination with trastuzumab, and chemotherapy in participants with advanced-stage HER2-positive colorectal cancer and breast cancer.

Start Date30 May 2024

Sponsor / Collaborator

Enliven Therapeutics, Inc. /US/Startup

100 Clinical Results associated with Eribulin mesylate

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100 Translational Medicine associated with Eribulin mesylate

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100 Patents (Medical) associated with Eribulin mesylate

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934

Literatures (Medical) associated with Eribulin mesylate

01 Feb 2024·Breast cancer research and treatment

Interleukin-6 and C-Reactive protein in metastatic breast cancer patients treated with eribulin

Letter

Author: Altundag, Kadri

29 Jan 2024·Cancer research communications

Phase II Study of the Liposomal Formulation of Eribulin (E7389-LF) in Combination with Nivolumab: Results from the Small Cell Lung Cancer Cohort

Article

Author: Yamamoto, Noboru ; Shiroyama, Takayuki ; Otake, Yohei ; Kobayashi, Haruki ; Sugawara, Shunichi ; Fujimoto, Daichi ; Satouchi, Miyako ; Kaname, Shota ; Murakami, Shuji ; Izumi, Hiroki ; Okishio, Kyoichi ; Matsuoka, Daiko ; Nishio, Makoto ; Tamiya, Motohiro ; Kozuki, Toshiyuki ; Takase, Takao ; Semba, Taro ; Azuma, Koichi ; Oya, Yuko ; Kawakami, Hisato

Abstract:

Purpose::

E7389-LF is a liposomal formulation of eribulin that contributes to tumor vascular remodeling. The phase II part of this phase Ib/II study assessed the efficacy/safety of E7389-LF in combination with nivolumab in several disease cohorts; herein, we report results from the small cell lung cancer (SCLC) cohort.

Experimental Design::

Patients with unresectable/measurable SCLC and disease progression with first-line platinum-based chemotherapy with/without an immune checkpoint inhibitor (ICI) were enrolled to receive E7389-LF 2.1 mg/m2 plus nivolumab 360 mg intravenously every 3 weeks. The primary objective of this part was to assess the objective response rate (ORR). Secondary objectives included assessments of safety and progression-free survival (PFS); exploratory assessments included overall survival (OS) and biomarkers.

Results::

Thirty-four patients were enrolled. By the data cut-off date (May 31, 2022), 29 (85.3%) had discontinued. Efficacy/biomarker analyses included 33 patients (1 had their diagnosis changed postenrollment); the ORR of E7389-LF plus nivolumab was 24.2% [95% confidence interval (CI): 11.1–42.3], the median PFS was 3.98 months (95% CI: 2.63–4.40), and, at a median follow-up of 10.6 months, the median OS was not reached (95% CI: not estimable). Notably, 27 of 33 patients (81.8%) had received an ICI as their prior first-line therapy. Treatment-related, treatment-emergent adverse events occurred in 97.1% (any grade) and 82.4% (grade ≥3) of enrolled patients; the most common event was neutropenia. Changes in vascular and immune-related plasma markers were observed.

Conclusions::

E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg every 3 weeks showed notable antitumor activity as second-line therapy for SCLC; no new safety signals were observed compared with either agent as monotherapy.

Significance::

This phase II part of a phase Ib/II study assessed liposomal eribulin (E7389-LF) plus nivolumab in 34 patients with pretreated SCLC; 8 of 33 evaluable patients (including 6/27 pretreated with ICIs) had objective responses. The combination was tolerable; increases in vasculature-related biomarkers tended to correlate with responses.

01 Jan 2024·Therapeutic advances in medical oncology

Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma

Article

Author: Azinovic, Ignacio ; Fernandéz-Rodríguez, Ricardo ; Alvarez, Cristina ; Hindi, Nadia ; Gutierrez, Antonio ; Sevillano, Alberto ; Olarte-García, Alicia ; Ortega, Justo ; Galvez-Montosa, Fernando ; Salgado, Lurdes ; Guzman-Gomez, Laura ; Carrasco-García, Irene ; Martin-Broto, Javier ; Peinado-Serrano, Javier ; Moura, David S ; Ferreira, Marta Ribeiro ; Rincon-Perez, Inmaculada

Background and objectives::

Dimensional response is an unmet need in second lines of advanced soft tissue sarcomas (STS). Indeed, the three approved drugs, pazopanib, trabectedin, and eribulin, achieved an overall response rate (ORR) of less than 10%. This fact potentially hinders the options for fast symptomatic relief or surgical rescue. The combination of trabectedin plus low-dose radiation therapy (T-XRT) demonstrated a response rate of 60% in phase I/II trial, while real-life data achieved 32.5% ORR, probably due to a more relaxed timing between treatments. These results were obtained in progressing and advanced STS. In this study, the merged databases (trial plus real life) have been analyzed, with a special focus on leiomyosarcoma patients.

Design and methods::

As responses were seen in a wide range of sarcoma histologies (11), this study planned to analyze whether leiomyosarcoma, the largest subtype with 26 cases (30.6%) in this series, exhibited a better clinical outcome with this therapeutic strategy. In addition, four advanced and progressing leiomyosarcoma patients, all with extraordinarily long progression-free survival of over 18 months, were collected.

Results::

A total of 847 cycles of trabectedin were administered to 85 patients, with the median number of cycles per patient being 7 (1–45+). A trend toward a longer progression-free survival (PFS) was observed in leiomyosarcoma patients with median PFS (mPFS) of 9.9 months [95% confidence interval (CI): 1.1–18.7] versus 5.6 months (95% CI: 3.2–7.9) for the remaining histologies, p = 0.25. When leiomyosarcoma and liposarcoma were grouped, this difference reached statistical significance, probably due to the special sensitivity of myxoid liposarcoma. The mPFS for L-sarcomas was 12.7 months (95% CI: 7–18.5) versus 4.3 months (95% CI: 3.3–5.3) for the remaining histologies, p = 0.001. Cases with long-lasting disease control are detected among leiomyosarcoma patients.

Conclusion::

Even when extraordinarily long-lasting responses do exist among leiomyosarcoma patients treated with T-XR, we were unable to demonstrate a significant difference favoring leiomyosarcoma patients in clinical outcomes.

66

News (Medical) associated with Eribulin mesylate

01 Jul 2024

·pipelinereview.com

Eisai announces move to solo development and commercialization of farletuzumab ecteribulin (Fzec) antibody drug conjugate (ADC)

Strategic collaboration with Bristol Myers Squibb ended TOKYO, Japan I July 01, 2024 I Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has agreed to end its global strategic collaboration with Bristol Myers Squibb for the co-development and co-commercialization of farletuzumab ecteribulin (FZEC), formerly known as MORAb-202, a folate receptor alpha (FRα)-targeting antibody drug conjugate (ADC) due to ongoing portfolio prioritization efforts within Bristol Myers Squibb. Based on the agreement, Eisai now owns all rights to FZEC and will solely conduct the global development and commercialization of the agent. Eisai will accelerate the development of the agent as a high priority with the hope to deliver it to patients as early as possible. Eisai plans to refund a part of the unused portion of the $200 million payment it received towards research and development expenses from Bristol Myers Squibb under the collaboration agreement and record the remaining as other income. FZEC is Eisai’s first ADC and is composed of Eisai’s in-house developed farletuzumab, a humanized IgG1 monoclonal antibody that binds to the FRα, and Eisai’s in-house developed anticancer agent eribulin, using an enzymatically cleavable linker. Currently, three clinical studies are ongoing: Eisai’s Phase 1/2 study for solid tumors (NCT04300556), and Bristol Myers Squibb’s Phase 2 studies for ovarian, peritoneal and fallopian tube cancers (NCT05613088) and non-small cell lung cancer (NCT05577715). Eisai positions oncology as a key franchise area and aims to contribute toward the cure of cancers by exploring the depths of human biology. FZEC development for refractory cancers is a testament of our dedication to addressing the unmet medical needs of patients with cancer. Eisai will make continuous efforts to increase the benefits provided to patients with cancer and their families. [Notes to editors] 1. Farletuzumab ecteribulin (FZEC, formerly known as MORAb-202) FZEC is Eisai’s first antibody drug conjugate (ADC) and that is composed of Eisai’s in-house developed farletuzumab, a humanized IgG1 monoclonal antibody that binds to the folate receptor alpha (FRα), and Eisai’s in-house developed anticancer agent eribulin, using an enzymatically cleavable linker. After FZEC enters the target FRα-positive cancer cells, it is thought that the linker is enzymatically cleaved, releasing eribulin from the antibody leading to its antitumor activity. When the anticancer agent and antibody components of an ADC are separated inside a targeted antigen-positive cancer cell, it is theorized that the released anticancer agent also has a bystander effect on neighboring antigen-negative cancer cells and the component cells of the tumor microenvironment. In pre-clinical studies, FZEC demonstrated a bystander effect*, with antitumor activity on the FRα-negative cancer cells surrounding the FRα-positive cancer cells. The payload eribulin was the first in the halichondrin class of microtubule dynamics inhibitor. Structurally, eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai, and functions by inhibiting the growth phase of microtubule dynamics which prevents cell division. Eribulin has been approved in countries including Japan, the United States, China, in Europe and in Asia for use in the treatment of advanced breast cancer and liposarcoma (soft tissue sarcoma in Japan). *Bystander effect: When the anticancer agent and antibody parts of an ADC are separated inside a targeted antigen-positive cancer cell, the released anticancer agent also affects neighboring antigen-negative cancer cells and the component cells of the cancer microenvironment. SOURCE: Eisai

License out/inADCPhase 2Drug ApprovalPhase 1

01 Jul 2024

·www.biopharmadive.com

Eisai and Bristol Myers cancel cancer ADC deal

Dive Brief:Eisai and Bristol Myers Squibb will cancel a collaboration on a dual-acting drug being developed to treat lung and ovarian cancer, Eisai said Monday. The termination is the result of the U.S. drugmakers portfolio prioritization efforts, Eisai said, likely referring to actions announced by Bristol Myers in April.The Japan-based drugmaker will refund part of a $200 million payment Bristol Myers paid upfront to finance research and development costs for farletuzumab ecteribulin.The two companies inked the collaboration deal in 2021, which included a total of $650 million in upfront payments and up to $2.5 billion in milestone payments. It signaled Bristol Myers interest in antibody-drug conjugates, or ADCs, which other drugmakers have brought to market. Bristol Myers has yet to follow.Dive Insight:Like all other ADCs, farletuzumab ecteribulin combines the targeting capabilities of engineered antibodies with the tumor-killing potency of chemotherapy. Eisais drug the first of this type its developed uses an antibody that homes in on a protein called folate receptor alpha, found in high concentration in lung, ovarian and other types of cancer. Its linked to a chemotherapy based on Eisais marketed breast cancer drug Halaven.The partners have advanced it as far as Phase 2 trials in chemotherapy-resistant ovarian cancer and non-small cell lung cancer that has spread beyond the lungs, both sponsored by Bristol Myers. Eisai still has its first-in-human Phase 1 trial in solid tumors underway, where its being studied in breast and endometrial cancer in addition to lung and ovarian disease.In the wake of the deals termination, Eisai said it will now accelerate the development of the agent as a high priority with the hope to deliver it to patients as early as possible.For Bristol Myers, it has since signed ADC deals with SystImmune, for $800 million upfront, and Orum Therapeutics, for $100 million upfront. The second of those two deals involves an antibody paired with a protein degrader drug rather than a chemotherapeutic.But like other large drugmakers, Bristol Myers has recently undertaken a review of its business ahead of expected patent expirations for many of its biggest products. In its April restructuring announcement, the company said it will lay off 2,200 employees, or 6% of its workforce, and had discontinued 12 experimental drugs. '

Phase 1ADCPhase 2License out/in

01 Jul 2024

·www.biospace.com

Eisai Assumes Sole Responsibility for ADC After Collaboration With BMS Ends

Pictured: 3D illustration of antibody-drug conjugates carrying toxic payloads/iStock, Love Employee Eisai announced on Monday that Bristol Myers Squibb has ended their global strategic agreement and the Japanese pharma will now exclusively own and be responsible for the investigational antibody-drug conjugate farletuzumab ecteribulin. With the termination of the collaboration, Eisai will “solely conduct the global development and commercialization” of farletuzumab ecteribulin, which is currently being assessed in a Phase I/II study in solid tumors. The antibody-drug conjugate (ADC) is also in a Phase II trial for ovarian, peritoneal and fallopian tube cancers, as well as a mid-stage study for non-small cell lung cancer. Eisai will “accelerate” the development of farletuzumab ecteribulin and treat it as a high priority to “deliver it to patients as early as possible,” according to the pharma. As part of the termination, Eisai will also refund BMS $200 million, which represents the unused portion of the initial R&D funds it received under the original agreement. The Japanese multinational will “record the remaining as other income.” Eisai and BMS first announced their global collaboration in June 2021, which saw the New Jersey pharma pay $650 million upfront plus the $200 million sum meant to shoulder Eisai’s R&D expenses. Under the deal, Eisai was also eligible for up to $2.45 billion in development, regulatory and commercial milestones. In return, BMS received the right to jointly develop and commercialize farletuzumab ecteribulin—which at the time was still called MORAb-202—in selected territories including the U.S., Canada, Europe, Japan and China. The decision to assume sole responsibility for farletuzumab ecteribulin is due to BMS’ “ongoing portfolio prioritization efforts,” according to Eisai’s announcement. In its first quarter 2024 business report, BMS announced that it was launching a sweeping “strategic productivity initiative” aimed at cost savings of $1.5 billion by the end of 2025. The strategic realignment includes around 2,200 layoffs, optimizing operations and pipeline cuts, though at the time farletuzumab ecteribulin wasn’t among the candidates that the pharma decided to drop. Farletuzumab ecteribulin is an investigational ADC that uses a humanized IgG1 monoclonal antibody targeting the FRα protein, which is highly expressed in several types of cancers. The ADC’s toxic payload is eribulin, an inhibitor of microtubule dynamics. When released inside cancer cells, eribulin prevents cell division and can trigger cell death. Eisai’s ADC also exerts a bystander effect on nearby cancer cells, providing an anti-tumor effect on neighboring malignant cells that might not express FRα. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

ADCLicense out/inPhase 2Phase 1

100 Deals associated with Eribulin mesylate

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External Link

KEGG	Wiki	ATC	Drug Bank
D08914	Eribulin mesylate	L01XX41	DB08871

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Sarcoma	JP	Eisai Co., Ltd.	29 Feb 2016
Soft Tissue Neoplasms	JP	Eisai Co., Ltd.	29 Feb 2016
Breast Cancer	JP	Eisai Co., Ltd.	22 Apr 2011
Liposarcoma	EU	Eisai GmbH	17 Mar 2011
Liposarcoma	IS	Eisai GmbH	17 Mar 2011
Liposarcoma	LI	Eisai GmbH	17 Mar 2011
Liposarcoma	NO	Eisai GmbH	17 Mar 2011
Locally advanced breast cancer	EU	Eisai GmbH	17 Mar 2011
Locally advanced breast cancer	IS	Eisai GmbH	17 Mar 2011
Locally advanced breast cancer	LI	Eisai GmbH	17 Mar 2011
Locally advanced breast cancer	NO	Eisai GmbH	17 Mar 2011
Metastatic breast cancer	US	Eisai, Inc.	15 Nov 2010

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast cancer recurrent	Phase 3	US	National Cancer Institute	17 Jan 2014
Invasive Mammary Carcinoma	Phase 3	US	National Cancer Institute	17 Jan 2014
HER2-negative breast cancer	Phase 3	CN	Eisai Co., Ltd.	26 Sep 2013
Triple Negative Breast Cancer	Phase 3	CN	Eisai Co., Ltd.	26 Sep 2013
Advanced Lung Non-Small Cell Carcinoma	Phase 3	US	Eisai, Inc.	09 Dec 2011
Advanced Lung Non-Small Cell Carcinoma	Phase 3	JP	Eisai, Inc.	09 Dec 2011
Advanced Lung Non-Small Cell Carcinoma	Phase 3	AU	Eisai, Inc.	09 Dec 2011
Advanced Lung Non-Small Cell Carcinoma	Phase 3	FR	Eisai, Inc.	09 Dec 2011
Advanced Lung Non-Small Cell Carcinoma	Phase 3	DE	Eisai, Inc.	09 Dec 2011
Advanced Lung Non-Small Cell Carcinoma	Phase 3	HK	Eisai, Inc.	09 Dec 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


JPRN-UMIN000027938 \| JPRN-jRCTs021180027 \| NCT03264547 (EMERALD, ASCO2024) Manual	Phase 3	HER2 Positive Breast Cancer First line HER2 Positive	446	Eribulin + HP	iokdibnsfl(egwyvfbood) = vemqdnaoqb kjiqvodxvl (xwgludaohd ) View more	Positive	24 May 2024
	Phase 3	HER2 Positive Breast Cancer First line HER2 Positive	446	Docetaxel/paclitaxel + HP	iokdibnsfl(egwyvfbood) = pgawridejs kjiqvodxvl (xwgludaohd ) View more	Positive	24 May 2024
ASCO2024	Not Applicable	Advanced breast cancer Ki67 \| HR+/HER2− \| triple-negative BC ... View more	89	Eribulin monotherapy	lnjhyycgjw(brrzbiowkj) = ikqrsbmipg bexzzdefnu (uxglvqtrfl, 3.5 - 8.5) View more	Positive	24 May 2024
ASCO2024	Not Applicable	Recurrent Ewing Sarcoma Second line	17	Eribulin and irinotecan	hmeprngqyu(guitmuoiqg) = pgpwoyilic pykxrawocx (eaazqhjkqn ) View more	Negative	24 May 2024
NCT05263882 (ASCO2024)	Phase 2	Second line HER2-negative	70	Eribulin plus gemcitabine	jgbzzilojt(pdmpuhtvkj) = neutropenia (38.6%), leukopenia (31.4%), anemia (24.3%), and thrombocytopenia (15.7%) mpgoudlbbb (cttyzqtjjq ) View more	Positive	24 May 2024
NCT04579224 (SWOG S1937, ASCO2024)	Phase 3	FGFR alterations	184	Eribulin + Gemcitabine	jcumyhfzgs(essqkywiat) = whkabreche mkusiqhwtc (xisyalewpj ) View more	Positive	24 May 2024
ASCO2024	Not Applicable	Metastatic breast cancer Second line	189	Eribulin as 2nd line chemotherapy	ypmipblgsj(sgtuqpzgzj) = mqvervsaki uyenyxikpp (wzweeawxnx ) View more	Positive	24 May 2024
ASCO2024	Not Applicable	Metastatic breast cancer Second line	189	Eribulin as 3rd line chemotherapy	ypmipblgsj(sgtuqpzgzj) = umpptcrkzb uyenyxikpp (wzweeawxnx ) View more	Positive	24 May 2024
ASCO2024	Not Applicable	Hormone Receptor Positive Breast Adenocarcinoma HR-positive	62	Eribulin monotherapy	cqzatsccdj(yfdpuenzqy) = xlsotfwhoo ymwbbpjgts (xxpyssoveq ) View more	Positive	24 May 2024
ASCO2024	Not Applicable	Hormone Receptor Positive Breast Adenocarcinoma HR-positive	62	Eribulin-based combination therapy	lllpssyukl(pgqoumgodj) = adkyfjduth idbngyqxuo (wcksozzusp )	Positive	24 May 2024
EMBRACE (ASCO2024)	Phase 3	Breast Cancer HER2 positive \| triple negative	205	Eribulin	jzphwighgd(lsecgyfmlh) = ljuvaoqowp cyudpilqfc (liaalhqobp ) View more	Negative	24 May 2024
NCT02640508 (NCT02640508, CTgov)	Phase 2	Advanced Malignant Solid Neoplasm	29	eribulin+Lenvatinib	ladajftetu(ttgojybamd) = vlsmwihfkc frtggglygs (sbvmfhuzgp, jqofzibgeu - ndqgujivif) View more	-	09 May 2024
NCT01554371 (A phase Ib/II study of eribulin in combination with cyclophosphamide, Pubmed)	Phase 1/2	Advanced breast cancer hormone receptor-positive (HR +)/HER2- \| HR + /HER2 +	44	Eribulin + Cyclophosphamide	ynxclsqtid(csplhyjrxf) = bsywlcpywp igaqhsfonm (hwxswohanh ) View more	Positive	01 Jan 2024