sEphB4-HSA(sEphB4-HSA) - 药物靶点：EphB4_在研适应症：转移性尿路上皮癌，肌层浸润性膀胱癌，卡波西肉瘤_专利_临床

概要

基本信息

药物类型

融合蛋白

别名

EphB4-Human Serum Albumin、Human Serum Albumin-EphB4 conjugate、RECOMBINANT EPHB4-HSA FUSION PROTEIN

+ [3]

靶点

EphB4

作用方式

拮抗剂

作用机制

EphB4拮抗剂(B型肝配蛋白受体-4拮抗剂)

治疗领域

肿瘤感染泌尿生殖系统疾病+ [1]

在研适应症

转移性尿路上皮癌肌层浸润性膀胱癌卡波西肉瘤

非在研适应症

复发性急性淋巴细胞白血病伴有骨髓发育不良相关变化的急性髓系白血病晚期恶性实体瘤+ [26]

原研机构

VasGene Therapeutics, Inc.

在研机构

VasGene Therapeutics, Inc.

非在研机构

University of Southern California

权益机构-

最高研发阶段临床2/3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

Sequence Code 6571

Sequence Code 28895

关联

14

项与 sEphB4-HSA 相关的临床试验

NCT06493552

/ Recruiting临床2/3期

A Modular, Open Label, Randomized Phase II/III Trial to Assess Efficacy of Combining sEphB4-HSA (EphrinB2 Inhibitor) With Immunotherapy Regimens in Patients With EphrinB2-High Solid Tumors

Patients with solid tumors that have high expression levels of EphrinB2 are treated with regimens that include EphrinB2 inhibitor, sEphB4-HSA. The primary objective of this study is to demonstrate additive therapeutic benefit for sEphB4-HSA. The secondary objectives are to determine whether the sEphB4-HSA containing regimen is safe and whether the oncological endpoints of importance in each cohort improve as a result of treatment with sEphB4-HSA containing regimen relative to a predefined threshold or to a control arm in the cohort where available. Treatment continues until progression of disease or unacceptable toxicities arise.

开始日期2025-03-15

申办/合作机构

VasGene Therapeutics, Inc.

NCT03552796

/ Withdrawn临床1期IIT

A First-in-Human Phase I Study of Intravesical sEphB4-HSA in Patients With "BCG-Unresponsive" Bladder Carcinoma In Situ (CIS), Completely Resected High Grade Ta/T1, to Establish the Maximum Tolerated Dose (MTD) or Recommended Phase II Dose (RP2D)

This phase I trial studies the side effects and best dose of recombinant EphB4-HSA fusion protein (sEphB4-HSA), and to see how well it works in treating participants with bladder cancer that has come back or that isn't responding to bacillus Calmette-Guerin (BCG) vaccine treatment. sEphB4-HAS prevents tumor cells from multiplying and blocks several compounds that promote the growth of blood vessels that bring nutrients to the tumor. Giving sEphB4-HSA may work better in treating participants with bladder cancer.

开始日期2023-08-01

申办/合作机构

University of Southern California

[+1]

NCT03993106

/ Recruiting临床2期

A Phase II Study of sEphB4-HSA in Kaposi Sarcoma

sEphB-HSA may prevent tumor cells from multiplying and blocks several compounds that promote the growth of blood vessels that bring nutrients to the tumor. The purpose of this study is to learn if sEphB4-HSA will decrease the number or size of Kaposi sarcoma lesions in people.

开始日期2020-09-17

申办/合作机构

VasGene Therapeutics, Inc.

100 项与 sEphB4-HSA 相关的临床结果

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100 项与 sEphB4-HSA 相关的转化医学

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100 项与 sEphB4-HSA 相关的专利（医药）

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8

项与 sEphB4-HSA 相关的文献（医药）

2024-07-10·Oncotarget

Improved efficacy of pembrolizumab combined with soluble EphB4-albumin in HPV-negative EphrinB2 positive head neck squamous cell carcinoma

Article

作者: Gill, Parkash S. ; Duddalwar, Vinay ; King, Kevin George ; Quinn, David I. ; El-Khoueiry, Anthony B. ; Nieva, Jorge J. ; Gitlitz, Barbara J. ; Jackovich, Alexandra ; Thomas, Jacob Stephen ; Tsao-Wei, Denice ; Tiu-lim, Justin Wayne Wong

OBJECTIVEPatients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) after primary local therapy have low response rates with cetuximab, systemic chemotherapy or check point inhibitor therapy. Novel combination therapies with the potential to improve outcomes for patients with HNSCC is an area of high unmet need.METHODSThis is a phase II single-arm clinical trial of locally advanced or metastatic HNSCC patients treated with a combination of soluble EphB4-human serum albumin (sEphB4-HSA) fusion protein and pembrolizumab after platinum-based chemotherapy with up to 2 prior lines of treatment. The primary endpoints were safety and tolerability and the primary efficacy endpoint was overall response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). HPV status and EphrinB2 expression were evaluated for outcome.RESULTSTwenty-five patients were enrolled. Median follow up was 40.4 months (range 9.8 - 40.4). There were 6 responders (ORR 24%). There were 5 responders in the 11 HPV-negative and EphrinB2 positive patients, (ORR 45%) with 2 of these patients achieving a complete response (CR). The median PFS in HPV-negative/EphrinB2 positive patients was 3.2 months (95% CI 1.1, 7.3). Median OS in HPV-negative/EphrinB2 positive patients was 10.9 months (95% CI 2.0, 13.7). Hypertension, transaminitis and fatigue were the most common toxicities.DISCUSSIONThe combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC.

2023-01-20·Journal of Clinical Oncology

EphrinB2 Inhibition and Pembrolizumab in Metastatic Urothelial Carcinoma

Article

作者: Siddiqi, Imran ; Lara, Primo N. ; Gill, Inderbir S. ; Devitt, Michael ; Sadeghi, Sarmad ; Groshen, Susan ; Pal, Sumanta ; Quinn, David ; Ruel, Nora ; Gill, Parkash S. ; Jackovich, Alexandra ; Parikh, Mamta ; Dreicer, Robert ; Parikh, Rahul ; Dorff, Tanya ; Vogelzang, Nicholas ; Tsao-Wei, Denice ; Burgess, Earle

PURPOSE Patients with metastatic urothelial carcinoma have poor prognosis after failure of standard first-line chemotherapy. Immune check point programmed death 1-programmed death ligand 1 antibodies have low response rates and thus there exists a major unmet need. MATERIALS AND METHODS In this phase II trial, patients with metastatic urothelial carcinoma that recurred or progressed after platinum-based chemotherapy received soluble EphB4-human serum albumin (sEphB4-HSA) in combination with pembrolizumab. The primary end points were tolerability and overall survival (OS). The secondary end points were progression-free survival (PFS), objective response rate (ORR), duration of response, and toxicity. The expression of sEphB4-HSA target EphrinB2 was correlated with outcomes. RESULTS Seventy patients were enrolled. The median follow up was 22.9 months (range, 1.3-54.7). The regimen had acceptable toxicity. In the intent-to-treat analysis (N = 70), the median OS was 14.6 months (95% CI, 9.2 to 21.5). Twenty-six (37%) patients had an objective response (95% CI, 26 to 48). The median PFS was 4.1 (95% CI, 1.5 to 5.7) months. Forty-six (66%) patients expressed EphrinB2, and among them, the median OS was 21.5 months (95% CI, 12.4 to not reached), the ORR was 52% (95% CI, 37 to 67), including a complete response rate of 24% (11 of 46; 95% CI, 12 to 36). The median PFS was 5.7 (95% CI, 2.7 to 27.9) months. Response was maintained at 6, 12, and 24 months in 88%, 74%, and 69% of the patients, respectively. CONCLUSION The combination of sEphB4-HSA and pembrolizumab appears synergistic with improved OS and ORR compared with historical data for programmed death 1/programmed death ligand 1 monotherapy.

2022-12-01·Clinical Genitourinary Cancer

A Phase II Study of sEphB4-HSA in Metastatic Castration-Resistant Prostate Cancer

Article

作者: Sagar, Vinay ; Hussain, Maha ; Stadler, Walter M ; Martone, Brenda ; VanderWeele, David J ; Morgans, Alicia ; Kocherginsky, Masha ; Munir, Sabah ; Abdulkadir, Sarki

INTRODUCTIONEphrin receptors and their membrane-localized ligands induce bidirectional signaling and facilitate tumor-stroma interactions. Blocking the EphB4-EphrinB2 pathway, which can be accomplished by soluble EphB4 conjugated to human serum albumin (sEphB4-HSA), promotes cell death in preclinical models of aggressive prostate cancer. We hypothesized that targeting the EphB4-EphrinB2 pathway may serve as a therapeutic target in the treatment of metastatic castration resistant prostate cancer (mCRPC).PATIENTS AND METHODSWe conducted a single arm, phase II trial in patients with progressive mCRPC who had received no more than 3 prior therapies for mCRPC. sEphB4-HSA 1000 mg IV was administered every 2 weeks, extending to 3 weeks starting from cycle 7. The primary endpoint was confirmed prostate specific antigen (PSA) response rate. We employed a Simon 2-stage Minimax design with 15 patients in the first stage and 10 additional patients in the second stage.RESULTSFourteen eligible patients enrolled in the study with median age of 73.5 years (range: 52-83) and median baseline PSA of 65.11 ng/mL (range: 7.77-2850 ng/mL). Most patients received 3 prior therapies for mCRPC. The median treatment duration with sEphB4-HSA was 6.5 weeks (range: 2-35 weeks). Three patients experienced a serious adverse event potentially related to therapy, including 1 patient with a grade 5 event (cerebral vascular accident) possibly related to the study drug. No patient had a confirmed PSA response, and the study was stopped for futility. Thirteen patients had PSA progression. The median time to PSA progression was 28 days (90% CI: 28-42 days), and median time to radiologic progression was 55 days (90% CI: 54-72 days). Of 3 patients with measurable disease, 2 had stable disease and one had progressive disease.CONCLUSIONIn patients with mCRPC who progressed on prior second generation AR-targeted therapy, sEphB4-HSA monotherapy had no discernable anti-tumor activity.

100 项与 sEphB4-HSA 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14797

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
转移性尿路上皮癌	临床3期	美国	VasGene Therapeutics, Inc.	2025-03-15
肌层浸润性膀胱癌	临床3期	美国	VasGene Therapeutics, Inc.	2025-03-15
转移性去势抵抗性前列腺癌	临床2期	美国	VasGene Therapeutics, Inc.	2019-09-20
转移性前列腺癌	临床2期	美国	VasGene Therapeutics, Inc.	2019-09-20
卡波西肉瘤	临床2期	美国	VasGene Therapeutics, Inc.	2018-02-13
转移性非小细胞肺癌	临床前	美国	University of Southern California	2015-09-03
晚期恶性实体瘤	临床前	美国	VasGene Therapeutics, Inc.	2012-09-06
晚期恶性实体瘤	临床前	美国	University of Southern California	2012-09-06
复发性实体肿瘤	临床前	美国	VasGene Therapeutics, Inc.	2012-09-06
复发性实体肿瘤	临床前	美国	University of Southern California	2012-09-06

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04033432 (CTgov)	临床2期	转移性前列腺癌 \| 转移性去势抵抗性前列腺癌	14	Recombinant EphB4-HSA Fusion Protein	網廠範壓蓋製鑰窪簾鏇(齋鹽齋鏇淵襯鬱簾淵範) = 積廠顧遞網鬱壓膚觸壓鬱繭憲積糧積顧糧顧遞 (齋膚構觸餘製獵醖餘夢, 艱構蓋願鹹鹹範構餘遞 ~ 鹹顧壓網廠夢衊繭鹽憲) 更多	-	2022-04-27
NCT04033432 (ASCO_GU2022) 人工标引	临床2期	转移性去势抵抗性前列腺癌二线	14	EphB4-HSA	網糧鏇憲糧遞鹽艱範醖(鬱衊鏇獵艱選憲齋糧衊) = 鹹鹹築糧網構窪餘淵範廠觸鹽獵餘廠齋淵窪製 (醖鏇衊鏇築鏇獵繭繭窪 ) 更多	不佳	2022-02-16
NCT02717156 (ESMO 12021 \| ESMO 22021) 人工标引	临床2期	转移性尿路上皮癌	62	sEphB4-HSA+pembrolizumab	壓壓淵衊鏇願製夢繭鹽(夢繭窪艱構蓋積餘醖顧) = Median cycles of treatment 5 (range 1-36). 6 pts still on treatment , 5 pts off treatment without PD. 36 (52%) off treatment due to PD, 4 toxicities 1 grade (G) 3 arthralgia, 1 G3 edema, 1 G3 abdominal pain and 1 G3 supraventricular tachycardia, 4 died on treatment (1 organ failure attributed to P, 1 aspiration pneumonia, 2 decline in health status) 範鬱鏇網鑰繭鹹憲築蓋 (蓋艱膚願築網繭遞壓淵 ) 更多	积极	2021-09-17
				sEphB4-HSA+pembrolizumab (expressed B2)
NCT02495896 (ASCO 12020 \| ASCO 22020) 人工标引	临床1期	晚期胰腺腺癌 \| 胆道癌一线	44	gemcitabine+nab-paclitaxel+sEphB4-HSA (pancreatic cancers)	(淵獵鹹憲獵網遞簾醖鑰) = hypertension (n = 16; 36%), neutropenia (n = 15; 34%), anemia (n = 14; 32%), thrombocytopenia (n = 7, 16%), fatigue (n = 7, 16%). 夢顧蓋選窪壓衊夢蓋膚 (餘廠簾獵淵網製壓衊蓋 )	积极	2020-05-25
				gemcitabine+cisplatin+sEphB4-HSA (biliary cancers)