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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for bladder cancer, focusing on a protein called EphrinB2 found in some solid tumors. The treatment, sEphB4-HSA (a potential new drug), is being tested for effectiveness when combined with Pembrolizumab. Researchers aim to determine if this combination can effectively treat bladder cancer and ensure its safety for patients. Individuals with bladder cancer expressing EphrinB2 who have not received cancer treatment in the past year might be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to potentially groundbreaking advancements in bladder cancer therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of sEphB4-HSA and pembrolizumab is generally well-tolerated. Studies have found that this treatment, which targets specific proteins in cancer cells, is safe for most patients. In individuals with various solid tumors, including bladder cancer, this combination has not caused major safety issues.

One study found that pembrolizumab alone produced good results with minimal side effects in many patients. When combined with sEphB4-HSA, it continues to show promise. Another study reported that the combination is both well-tolerated and may work well together, especially in certain types of cancer.

In trials with previously untreated individuals, the combination also appears safe. Patients reported manageable side effects, indicating the treatment did not cause severe or unexpected health problems. Researchers believe this combination might be more effective than using each treatment alone.

Overall, evidence suggests that sEphB4-HSA and pembrolizumab together are safe for people with bladder cancer, with side effects that are usually mild and manageable. This makes it a potential option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sEphB4-HSA for bladder cancer because it targets the EphB4 receptor, which plays a role in tumor growth and blood vessel formation. Unlike traditional chemotherapy, which broadly attacks rapidly dividing cells, sEphB4-HSA offers a more targeted approach, potentially leading to fewer side effects. Additionally, when combined with pembrolizumab, an immunotherapy drug, it might enhance the body's immune response against bladder cancer cells, offering a promising new avenue for treatment.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

This trial will evaluate the combination of sEphB4-HSA with pembrolizumab for treating bladder cancer. Research has shown that this combination may help treat bladder cancer, with studies finding that 37% of patients experienced a reduction or disappearance of their cancer after this treatment. Additionally, this combination appears to extend patient survival compared to past data on pembrolizumab alone. The treatment targets a protein called EphrinB2, found in many solid tumors, and works well when this protein is present. Overall, it is generally well tolerated and could offer a new option for people with certain types of bladder cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Sarmad Sadeghi, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. urotoday.com urotoday.com/conference-highlights/esmo-2021/esmo-2021-bladder-cancer/132176-esmo-2021-phase-ii-trial-of-pembrolizumab-p-in-combination-with-sephb4-hsa-b4-in-previously-treated-metastatic-urothelial-carcinoma-muc.html

ESMO 2021: Phase II Trial of Pembrolizumab (P) in ... The combination of sEphB4-HSA and pembrolizumab demonstrated impressive activity. The ORR was 37% in the overall cohort with a complete response ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)02261-4/pdf

651O Phase II trial of pembrolizumab (P) in ... Conclusions: B4 + P is well tolerated and may have synergistic efficacy in mUC. B2 was expressed in the majority of pts and predicted for improved tx outcome.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02717156

Multicohort Phase II Trial of sEphB4-HSA+Pembrolizumab ... This is a multi-cohort single arm phase II/screening trial of the combination of a fusion protein that binds EphrinB2 and blocks interaction with cell surface ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11181698/

Clinical Trials Corner Issue 7(4) - PMC This trial evaluates the combination of pembrolizumab in combination with sEphB4-HSA in previously treated metastatic urothelial cancer with ...

5. studypages.com studypages.com/s/a-study-of-experimental-combination-therapy-with-pembrolizumab-and-sephb4-hsa-for-urothelial-carcinoma-bladder-cancer-843276/

A Study of Experimental Combination Therapy With ... This study is testing the combination of two experimental drugs: Pembrolizumab (by Merck & Co, Inc) and; sEphB4-HAS (by VasGene Therapeutics, Inc).

6. trialx.com trialx.com/clinical-trials/listings/317615/modular-trial-of-sephb4-hsa-in-ephrinb2-high-solid-tumors/

Modular Trial of sEphB4-HSA in EphrinB2-High Solid Tumors Cohort B will study the combination of sEphB4-HSA + Pembrolizumab in previously treated mUC, in EphrinB2-high subgroup, a group that in ...

7. withpower.com withpower.com/trial/sephb4-hsa-pembrolizumab-for-cancer-4652c

sEphB4-HSA + Pembrolizumab for Cancer In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06493552

Modular Trial of sEphB4-HSA in 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.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37806844/

Analysis of Safety and Efficacy of the PCR-MIB Phase 2 ... This study investigates the combination of pembrolizumab and chemoradiation (CRT) for muscle-invasive bladder cancer (MIBC).