sEphB4-HSA for Kaposi's Sarcoma

Recruiting at 2 trial locations

Overseen By Sarah E. Cole, M.S.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vasgene Therapeutics, Inc

Must be taking: Antiretrovirals

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Brain metastases, Recent major infarct, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 months

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called sEphB4-HSA (a recombinant fusion protein) for Kaposi's Sarcoma, a cancer that causes skin lesions. The goal is to determine if this drug can reduce the number or size of these lesions by stopping tumor growth and cutting off their blood supply. Participants will receive the treatment intravenously during an outpatient visit. This trial may suit individuals with biopsy-confirmed Kaposi's Sarcoma on their skin, regardless of previous treatments, who have not seen improvement in the past month. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain treatments like warfarin or full-dose anticoagulation, you may need to stop them 7 days before enrolling. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that sEphB4-HSA is likely to be safe for humans?

Research has shown that sEphB4-HSA has been tested in people with Kaposi sarcoma to assess its safety. The main goal of these studies was to determine if patients could tolerate the treatment without serious side effects. Reports suggest that most people handle the treatment well. However, mild side effects may occur, which is normal since the treatment remains under investigation.

It is important to remember that sEphB4-HSA is still under research, and ongoing trials continue to gather information about its safety and effectiveness. Those considering joining a trial should discuss the potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Kaposi's Sarcoma, which often involve chemotherapy or radiation, sEphB4-HSA works differently by targeting the EphB4 protein involved in the growth of cancer cells. This approach could potentially provide a more direct attack on the cancer, with fewer side effects compared to conventional methods. Researchers are excited about sEphB4-HSA because it is administered intravenously in just two doses per month, which might offer a more convenient and less burdensome treatment schedule for patients.

What evidence suggests that sEphB4-HSA might be an effective treatment for Kaposi's Sarcoma?

Research has shown that sEphB4-HSA might help treat Kaposi's sarcoma by stopping the growth of blood vessels that supply nutrients to tumors. In earlier studies, about 24% of patients responded to sEphB4-HSA, with nearly one in four experiencing a reduction in their cancer. This treatment reduces the number of blood vessels feeding tumors, potentially resulting in smaller or fewer cancer spots. It can also increase factors like VEGF and DLL4, which are linked to tumor shrinkage. These findings suggest that sEphB4-HSA could be a promising option for people with Kaposi's sarcoma. All participants in this trial will receive sEphB4-HSA. ^{2 5 6 7 8}

Who Is on the Research Team?

Carl Millner, M.D.

Principal Investigator

AIDS Healthcare Foundation

Are You a Good Fit for This Trial?

Adults with biopsy-proven Kaposi Sarcoma (skin or visceral) can join this trial. They must be over 18, have a life expectancy of more than 3 months, and be able to follow the study plan. People with HIV are eligible if they've been on stable antiretroviral therapy for at least 12 weeks. Women who can get pregnant and men must use birth control during the study.

Inclusion Criteria

I am committed to using two forms of birth control and agree to regular pregnancy tests if I can become pregnant.

I have skin lesions suitable for biopsy and at least five others that haven't improved in a month.

Your platelet count is at least 75,000 per microliter.

Exclusion Criteria

Participants who are receiving any other investigational agents

I haven't had a serious infection or been treated for one, except for oral thrush or genital herpes, in the last 14 days.

I haven't had cancer treatment for Kaposi's sarcoma in the last 4 weeks, or I've recovered from its side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sEphB4-HSA through intravenous infusion on Days 1 and 15 of each 4-week cycle

6 months

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may continue on study protocol as long as their KS is responding or stable

Indefinite

What Are the Treatments Tested in This Trial?

Interventions

• sEphB4-HSA

Trial Overview The trial is testing sEphB4-HSA, which may stop tumor cells from growing by blocking substances that help tumors get nutrients through blood vessels. The goal is to see if it reduces the number or size of Kaposi sarcoma lesions.

How Is the Trial Designed?

Group I: Study Drug Experimental Treatment 1 Intervention

All study participants will receive sEphB4-HSA through a needle in a vein in their arm for an hour in an outpatient clinic. All study participants will receive two doses of study drug on Days 1 and 15 of each 4 week cycle.

Who Is Running the Clinical Trial?

Vasgene Therapeutics, Inc

Lead Sponsor

Trials

9

Recruited

1,000+

Published Research Related to This Trial

Blocking EphrinB2 with a specially designed protein (sEphB4-HSA) significantly inhibited the migration and invasion of Kaposi sarcoma (KS) cells in laboratory tests, suggesting a potential therapeutic target.

The combination of sEphB4-HSA and a VEGF antibody showed enhanced effects, reducing blood vessel density and increasing hypoxia, indicating a promising new treatment strategy for KS that warrants further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Ephs, Ephrins, and growth factors in Kaposi sarcoma and implications of EphrinB2 blockade. Scehnet, JS., Ley, EJ., Krasnoperov, V., et al.[2021]

The study presents a novel cancer immunotherapy that combines high-affinity antibody fragments with CD8 T lymphocytes to effectively target and kill tumor cells, regardless of their self peptide-MHC expression.

In experiments with nude mice bearing human tumor xenografts, the recombinant fusion proteins demonstrated strong antitumor activity, suggesting a promising new approach to enhance cancer treatment by linking antibody and T cell responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-specific Ab-mediated targeting of MHC-peptide complexes induces regression of human tumor xenografts in vivo. Lev, A., Noy, R., Oved, K., et al.[2018]

The novel fusion protein Sm3E-TNF effectively targets tumors expressing carcinoembryonic antigen (CEA), achieving a remarkable tumor-to-blood accumulation ratio of 56:1, indicating high selectivity for cancer cells.

Combining Sm3E-TNF with oxaliplatin resulted in prolonged tumor stabilization and complete eradication in 40% of treated mice, suggesting a promising therapeutic strategy for colorectal cancer, while the combination with 5-fluorouracil reduced effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Antibody-Tumor Necrosis Factor Fusion Protein that Synergizes with Oxaliplatin for Treatment of Colorectal Cancer. Bajic, D., Chester, K., Neri, D.[2021]

The study developed a fusion protein (H2Kd/scPSMA) that combines a single chain antibody against prostate specific membrane antigen (PSMA) with a mouse MHC molecule, enhancing the immune recognition of tumor cells.

In animal models, expressing this fusion protein in melanoma cells significantly inhibited tumor growth and improved overall survival, suggesting a promising strategy for enhancing anti-tumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting foreign major histocompatibility complex molecules to tumors by tumor cell specific single chain antibody (scFv). Li, J., Franek, KJ., Patterson, AL., et al.[2018]

Immunization with the wildtype gH/gL complex was the most effective method for generating neutralizing antibodies against KSHV, as it inhibited both viral infection and receptor binding in mice.

Different vaccine formulations, including a gL-gHecto fusion protein and a ferritin construct, showed varying levels of efficacy, with the wildtype gH/gL and the fusion protein being equally effective in neutralizing KSHV, while the ferritin construct was less effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibodies Targeting KSHV gH/gL Reveal Distinct Neutralization Mechanisms. Fricke, T., Großkopf, AK., Ensser, A., et al.[2022]

The antigens ORF 65 and K8.1 of human herpesvirus 8 (HHV8) showed the highest reactivity (71%) in sera from HIV-dependent Kaposi's sarcoma patients, indicating their importance for HHV8 diagnostics.

PCR testing revealed that 48% of Kaposi's sarcoma patients had detectable HHV8 in their blood, and specific regions of the ORF 65 and K8.1 proteins were identified as crucial for eliciting immune responses, suggesting potential targets for diagnostic and therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the immunoglobulin-G-specific seroreactivity of different recombinant antigens of the human herpesvirus 8. Lang, D., Hinderer, W., Rothe, M., et al.[2006]

Synovial sarcoma (SS) shows high levels of cancer testis antigens (CTAs), making it a promising target for immunotherapy aimed at activating the immune system against these proteins, which are typically not found in normal tissues.

Current clinical trials are exploring vaccine and T-cell receptor-based therapies targeting specific CTAs like NY-ESO-1 and MAGE-A4, which could significantly improve treatment options for SS compared to existing standards of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting cancer testis antigens in synovial sarcoma. Mitchell, G., Pollack, SM., Wagner, MJ.[2021]

EphA4 has been identified as a new entry receptor for Kaposi's sarcoma-associated herpesvirus (KSHV), enhancing the virus's ability to fuse and infect target cells, particularly in HEK293T cells.

Both EphA2 and EphA4 are important for KSHV infection, with double-knockout cells showing the greatest reduction in fusion activity, suggesting that targeting these receptors could lead to new therapeutic strategies against KSHV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ephrin Receptor A4 is a New Kaposi's Sarcoma-Associated Herpesvirus Virus Entry Receptor. Chen, J., Zhang, X., Schaller, S., et al.[2021]

The novel biopharmaceutical, IL2-F8-TNFmut, effectively targets and eradicates solid tumors and hematologic malignancies in mice, showing selectivity for cancerous tissues while sparing healthy adult tissues, which suggests a promising safety profile.

This treatment not only eliminated tumors but also provided protective immunity against future tumor growth, indicating its potential for long-lasting therapeutic effects in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potency-matched Dual Cytokine-Antibody Fusion Proteins for Cancer Therapy. De Luca, R., Soltermann, A., Pretto, F., et al.[2022]

Kaposi sarcoma herpesvirus (KSHV) is linked to several serious diseases, including Kaposi sarcoma and primary effusion lymphoma, and its pathogenic potential is often triggered by immune deficiencies and inflammation.

Understanding KSHV's life cycle and its role in disease could lead to new treatments targeting viral proteins and pathways, as well as the potential development of a vaccine to prevent its transmission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kaposi sarcoma herpesvirus pathogenesis. Mariggiò, G., Koch, S., Schulz, TF.[2023]

Citations

1. georgiacancerinfo.org georgiacancerinfo.org/clinical-trials/detail/5231?cancerType=sarcoma

sEphB4-HSA in Treating Patients with Kaposi Sarcoma sEphB4-HSA protein may block the growth of blood vessels that provide blood to the cancer, and may also prevent cancer cells from growing.

2. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT01642342/

Clinical Trial: NCT01642342 Every 3 Weeks Treatment (sEphB4-HSA), Experimental, Patients receive recombinant EphB4-HSA fusion protein IV over 60 minutes on days 1.

3. synapse.patsnap.com synapse.patsnap.com/drug/c052f78a2e114eab80a3db097249ae72

sEphB4-HSA - Drug Targets, Indications, Patents RESULTS: Twenty-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 ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-09283

A Study of sEphB4-HSA in Kaposi Sarcoma - NCI The purpose of this study is to learn if sEphB4-HSA will decrease the number or size of Kaposi sarcoma lesions in people.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2614637/

The role of Ephs, Ephrins, and growth factors in Kaposi ... sEphB4-HSA reduced blood vessel density, pericyte recruitment, vessel perfusion, and increased hypoxia, with an associated increase in VEGF and DLL4 expression.

6. trial.medpath.com trial.medpath.com/clinical-trial/9a5bbb4ce7c2eea2/nct02799485-sephb4-hsa-treating-kaposi-sarcoma

sEphB4-HSA in Treating Patients With Kaposi Sarcoma SECONDARY OBJECTIVES: I. To assess the safety of sEphB4-HSA in participants with Kaposi sarcoma (KS). II. To determine trough level exposure of sEphB4-HSA and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02495896

NCT02495896 | Recombinant EphB4-HSA Fusion Protein ... This pilot phase Ib trial studies the side effects and best dose of recombinant EphB4-HSA fusion protein when given together with standard chemotherapy ...

8. centerwatch.com centerwatch.com/clinical-trials/listings/NCT02799485/sephb4-hsa-in-treating-patients-with-kaposi-sarcoma

sEphB4-HSA in Treating Patients With Kaposi Sarcoma I. To assess the safety of sEphB4-HSA in participants with Kaposi sarcoma (KS). II. To determine trough level exposure of sEphB4-HSA and ...