Delving into the Latest Updates on sEphB4-HSA with Synapse

Overview

Basic Info

Drug Type

Fusion protein

Synonyms

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

+ [3]

Target

EphB4

Mechanism

EphB4 antagonists(Ephrin type-B receptor 4 antagonists)

Therapeutic Areas

NeoplasmsInfectious DiseasesUrogenital Diseases+ [1]

Active Indication

Metastatic urothelial carcinomaMuscle Invasive Bladder CarcinomaKaposi Sarcoma

Inactive Indication

Acute lymphoblastic leukemia recurrentAcute Myeloid Leukemia with Myelodysplasia-Related ChangesAdvanced Malignant Solid Neoplasm+ [26]

Originator Organization

VasGene Therapeutics, Inc.

Active Organization

VasGene Therapeutics, Inc.

Inactive Organization

University of Southern California

Drug Highest PhasePhase 2/3

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 6571

Sequence Code 28895

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.

Start Date01 Nov 2024

Sponsor / Collaborator

VasGene Therapeutics, Inc.

NCT03552796 / WithdrawnPhase 1IIT

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.

Start Date01 Aug 2023

Sponsor / Collaborator

University of Southern California

[+1]

NCT03993106 / RecruitingPhase 2

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.

Start Date17 Sep 2020

Sponsor / Collaborator

VasGene Therapeutics, Inc.

100 Clinical Results associated with sEphB4-HSA

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100 Translational Medicine associated with sEphB4-HSA

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100 Patents (Medical) associated with sEphB4-HSA

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8

Literatures (Medical) associated with sEphB4-HSA

10 Jul 2024·Oncotarget

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

Article

Author: Gill, Parkash S. ; Duddalwar, Vinay ; El-Khoueiry, Anthony B. ; King, Kevin George ; Quinn, David I. ; 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.

20 Jan 2023·Journal of Clinical Oncology

EphrinB2 Inhibition and Pembrolizumab in Metastatic Urothelial Carcinoma

Article

Author: Siddiqi, Imran ; Lara, Primo N. ; Gill, Inderbir S. ; Devitt, Michael ; Sadeghi, Sarmad ; Groshen, Susan ; Pal, Sumanta ; Quinn, David ; Ruel, Nora ; Gill, Parkash S. ; Parikh, Mamta ; Jackovich, Alexandra ; 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.

01 Dec 2022·Clinical Genitourinary Cancer

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

Article

Author: 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 Deals associated with sEphB4-HSA

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14797

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic urothelial carcinoma	Phase 3	-	VasGene Therapeutics, Inc.	01 Nov 2024
Muscle Invasive Bladder Carcinoma	Phase 3	-	VasGene Therapeutics, Inc.	01 Nov 2024
Metastatic castration-resistant prostate cancer	Phase 2	US	VasGene Therapeutics, Inc.	20 Sep 2019
Metastatic Prostate Carcinoma	Phase 2	US	VasGene Therapeutics, Inc.	20 Sep 2019
Kaposi Sarcoma	Phase 2	US	VasGene Therapeutics, Inc.	13 Feb 2018
Squamous Cell Carcinoma of Head and Neck	Phase 2	US	University of Southern California	03 Sep 2015
Advanced Malignant Solid Neoplasm	Phase 2	US	VasGene Therapeutics, Inc.	06 Sep 2012
Advanced Malignant Solid Neoplasm	Phase 2	US	University of Southern California	06 Sep 2012
Relapsed Solid Neoplasm	Phase 2	US	VasGene Therapeutics, Inc.	06 Sep 2012
Relapsed Solid Neoplasm	Phase 2	US	University of Southern California	06 Sep 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Pubmed	Phase 2	Metastatic castration-resistant prostate cancer	-	sEphB4-HSA 1000 mg IV	(wjjlsyxqty) = 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 zjyigkurpu (fpaaekispv )	Negative	07 Sep 2022
NCT04033432 (CTgov)	Phase 2	Metastatic Prostate Carcinoma \| Metastatic castration-resistant prostate cancer	14	Recombinant EphB4-HSA Fusion Protein	hujvwbkoux(lokqgybsui) = kdjfhzgqkx bczntskomi (omlulqtgyr, lzkuyqvafi - leipsfqvxk) View more	-	27 Apr 2022
NCT04033432 (ASCO_GU2022) Manual	Phase 2	Metastatic castration-resistant prostate cancer Second line	14	EphB4-HSA	xtnpfpzksv(rlmltalzlz) = tbwxnyrpkx rfyreyoonf (qbjefvukjy ) View more	Negative	16 Feb 2022
NCT02717156 (ESMO2021) Manual	Phase 2	Metastatic urothelial carcinoma	62	sEphB4-HSA+pembrolizumab	ogfnefdiir(vmzhntzjgy) = 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) adikthrgev (uqqwyjetot ) View more	Positive	17 Sep 2021
NCT02717156 (ESMO2021) Manual	Phase 2	Metastatic urothelial carcinoma	62	sEphB4-HSA+pembrolizumab (expressed B2)		Positive	17 Sep 2021
NCT02495896 (ASCO2020) Manual	Phase 1	Advanced Pancreatic Adenocarcinoma \| Biliary Tract Neoplasms First line	44	gemcitabine+nab-paclitaxel+sEphB4-HSA (pancreatic cancers)	(crbjstitce) = hypertension (n = 16; 36%), neutropenia (n = 15; 34%), anemia (n = 14; 32%), thrombocytopenia (n = 7, 16%), fatigue (n = 7, 16%). jzcbngkmol (eazaeeoooi )	Positive	25 May 2020
NCT02495896 (ASCO2020) Manual	Phase 1		44	gemcitabine+cisplatin+sEphB4-HSA (biliary cancers)		Positive	25 May 2020