sEphB4-HSA for Bladder Cancer

Overseen By Jon Cogan, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Vasgene Therapeutics, Inc

Must not be taking: Corticosteroids

Disqualifiers: Brain metastases, Autoimmune disorders, Infections, 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

Compensation: Varies

Number of Visits: 1

Duration: 4 cycles

700 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that you should not have had systemic therapy for cancer in the previous 12 months.

How does the drug sEphB4-HSA work for bladder cancer?

sEphB4-HSA is unique because it targets the EphB4 receptor, which is overexpressed in bladder cancer cells, leading to tumor cell death and reduced blood vessel formation in tumors. This approach is different from traditional chemotherapy as it directly targets cancer cell survival mechanisms and has shown significant tumor regression in studies. ^{1 2 3 4 5}

Research Team

Sarmad Sadeghi, MD

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for men and women over 18 with thyroid, bladder, or urothelial cancer that's high in EphrinB2. They must provide biopsy tissue, not be breastfeeding, use contraception if applicable, and have a good performance status (able to carry out daily activities).

Inclusion Criteria

Women must not be breastfeeding

Module A Inclusion Criteria: Urothelial carcinoma, variant components and differentiations allowed. Pure small cell not allowed; cT2 to cT4a N0M0, by TURBT or imaging; No systemic therapy for cancer in the previous 12 months; Choice of treatment if randomized to the control arm must be declared prior to randomization. If cisplatin ineligible or refusing, pembrolizumab must be approved by patient's insurance prior to randomization

Willing and able to provide informed consent

Exclusion Criteria

History of severe hypersensitivity reaction to any monoclonal antibody

My adrenal glands are not working properly and it's not under control.

I have an ongoing liver disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sEphB4-HSA + Pembrolizumab or other regimens based on cohort assignment. Treatment continues until disease progression or unacceptable toxicities.

4 cycles

Visits on days 1 and 8 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment. Imaging assessments every 6 weeks for the first 3 months, then every 12 weeks.

Up to 60 months

Extension

Participants may continue to receive treatment if they benefit and tolerate it well, as per protocol.

Long-term

Treatment Details

Interventions

• sEphB4-HSA

Trial Overview The study tests sEphB4-HSA combined with other drugs like Enfortumab vedotin and Pembrolizumab against solid tumors high in EphrinB2. It aims to see if adding sEphB4-HSA improves treatment outcomes compared to standard options.

Participant Groups

Group I: sEphB4-HSA + Pembrolizumab in Naive mUC Experimental Treatment 2 Interventions

sEphB4-HSA shall be started at a dose of 10mg/kg using actual body weight and administered IV over 60 minutes on days 1 and 8 of each cycle as outlined under section 7.1.3. Trial treatment may be administered up to 3 days before or after the scheduled Day 1 of each cycle due to administrative reasons. All trial treatments will be administered on an outpatient basis unless the patient has been admitted for another reason and meets all criteria for further therapy. Pembrolizumab dose, schedule, delays, and discontinuation of therapy shall be determined by the treating physician in accordance with product label(s), standard of care and institutional policies. Treatment will continue until the prespecified number of cycle of therapy are completed or until progression of disease or unacceptable toxicities where specified by the protocol for specific cohort(s).

Group II: sEphB4-HSA + Pembrolizumab in MIBC Experimental Treatment 2 Interventions

sEphB4-HSA shall be started at a dose of 10mg/kg using actual body weight and administered IV over 60 minutes on days 1 and 8 of each cycle as outlined under section 7.1.3. Trial treatment may be administered up to 3 days before or after the scheduled Day 1 of each cycle due to administrative reasons. All trial treatments will be administered on an outpatient basis unless the patient has been admitted for another reason and meets all criteria for further therapy. Pembrolizumab dose, schedule, delays, and discontinuation of therapy shall be determined by the treating physician in accordance with product label(s), standard of care and institutional policies. Treatment will continue until the prespecified number of cycle of therapy are completed or until progression of disease or unacceptable toxicities where specified by the protocol for specific cohort(s).

Group III: Enfortumab Vedotin (EV) + Pembrolizumab in Naive mUC Active Control 2 Interventions

Dose modification, delays and discontinuation of therapy shall be determined by the treating physician in accordance with product label(s), standard of care and institutional policies.

Group IV: Gemcitabine-Cisplatin (GC) or Pembrolizumab Alone in MIBC Active Control 3 Interventions

Dose modification, delays and discontinuation of therapy shall be determined by the treating physician in accordance with product label(s), standard of care and institutional policies.

Who Is Running the Clinical Trial?

Vasgene Therapeutics, Inc

Lead Sponsor

Trials

9

Recruited

1,000+

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Targeted Inhibition of P4HB Promotes Cell Sensitivity to Gemcitabine in Urothelial Carcinoma of the Bladder. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB. [2023]

3. England pubmed.ncbi.nlm.nih.gov

EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

B7-Homolog 4 Promotes Epithelial-Mesenchymal Transition and Invasion of Bladder Cancer Cells via Activation of Nuclear Factor-κB. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The differential expression of EphB2 and EphB4 receptor kinases in normal bladder and in transitional cell carcinoma of the bladder. [2022]