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Muscle-Invasive Bladder CarcinomaPhase 2/3NCT06493552

Modular Trial of sEphB4-HSA in EphrinB2-High Solid Tumors

A Phase 2/3 study testing SEphB4-HSA, Pembrolizumab and Gemcitabine in people with Muscle-Invasive Bladder Carcinoma and Metastatic Urothelial Carcinoma, run by Vasgene Therapeutics, Inc at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
SEphB4-HSA, Pembrolizumab and Gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
700 participants
Where
1 siteUnited States
Study dates
15 Mar 2025to Aug 2034
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • General Inclusion Criteria for Both Arms
  • Willing and able to provide informed consent.
  • Men and women 18 years of age, or older.
  • Must provide the cell block or a minimum of 15 slides from the diagnostic biopsy or archival tissue.
  • Tumor tissue must be submitted for molecular profile through a commercial service such as Tempus, CARIS, Foundation One, etc. This must include a PD-L1 assay.
  • Tumor must express EphrinB2 as assessed by USC Norris Core Lab.
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  • Zubrod performance status of less than or equal to 1.
  • Women of childbearing potential must use method(s) of contraception. The individual methods of contraception should be determined in consultation with the treating physician or investigator.
  • Women of childbearing potential are eligible if serum pregnancy test obtained during screening is negative. Women are also eligible if one of the following criteria is met:
  • Have undergone a documented hysterectomy and/or bilateral oophorectomy; OR
  • Have medically confirmed ovarian failure; OR
  • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; OR
  • A serum follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal women.
  • Women must not be breastfeeding.
  • Men who are sexually active with women of childbearing potential must agree to use 2 contraceptive methods with a failure rate of less than 1% per year.
  • o NOTE: Contraception should be continued using two highly effective methods for a period of 120 days after the last dose of treatment.
  • Adequate organ function as defined below using baseline laboratory requirements obtained within 14 days prior to randomization:
  • Measured or calculated creatinine clearance (CrCl) greater than or equal to 30 mL/min using the Cockcroft-Gault formula using actual weight (NOT ideal or adjusted weights).
  • WBC ≥2000/uL
  • Neutrophils ≥1500/uL
  • Platelets ≥100x103/uL
  • Hemoglobin ≥9g/dL
  • AST ≤3 x ULN
  • ALT ≤3 x ULN
  • Bilirubin ≤1.5 x ULN
  • 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.
  • Module B inclusion Criteria
  • Urothelial carcinoma, variant components and differentiations allowed. Pure small cell not allowed.
  • Tumor must be Nectin4 non-amplified- testing performed during pre-screening assessment.
  • No systemic therapy for cancer in the previous 12 months.
  • Measurable disease as defined by RECIST1.1 criteria

Who cannot join

  • Patients with known symptomatic brain metastases requiring systemic corticosteroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable. Mild neurological deficit is allowed, if it does not interfere with the ability to judge the safety on the trial.
  • History of or active autoimmune disorders (including but not limited to: Crohn's Disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Grave's disease) and other conditions that compromise or impair the immune system.
  • Known active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) -related illness. Routine testing is not required; however, treating physicians may use their discretion to determine whether testing is necessary.
  • Uncontrolled adrenal insufficiency.
  • Any known active chronic liver disease.
  • Concurrent or active second malignancy requiring systemic therapy is excluded.
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  • Known medical condition (eg, a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
  • Major surgery less than 6 weeks prior to the first dose of study drug. Minor surgery less than 4 weeks prior to the first dose of study drug. Insertion of vascular access device ≥ 7 days prior to 1st dose of study drug is allowed.
  • History of severe hypersensitivity reaction to any monoclonal antibody.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jon Cogan, MS contact

323-221-7818

info@vasgene.com

United States1 site, 1 recruiting

  • Sarcoma Oncology Center

    Santa Monica, California, 90403

    Victoria Chua, 310-552-9999, vchua@sarcomaoncology.com

    Sant Chawla, M.D.

    Recruiting

Other trials in United States

About this study

Official title: 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.

Read the detailed description

The investigators hypothesize that the inhibition of EphrinB2 overcomes the negative prognostic impact of this biomarker and improves the treatment outcomes. It is further hypothesized that this higher level of activity is attributable to the synergistic immune-stimulatory effect of sEphB4-HSA when combined with pembrolizumab.

Cohort A is designed to treat patients with MIBC whose tumors express EphrinB2. Patients in this cohort will be randomized to receive sEphB4-HSA + Pembrolizumab or Gemcitabine-Cisplatin (GC) regimen per standard of care of 4 cycle. Patients ineligible for cisplatin-based chemotherapy or refusing such chemotherapy will be able to receive pembrolizumab alone for 4 cycles based on PURE-01 data showing comparable response rate to chemotherapy with GC regimen.

Cohort B will study the combination of sEphB4-HSA + Pembrolizumab in previously treated mUC, in EphrinB2-high subgroup, a group that in previous studies demonstrated a 52% response rate. In the multi-institutional retrospective series reported by the study team, the expected response rate for anti-PD-L1/PD-1 antibodies is 12% among tumors with high EphrinB2 expression. This represents more than 4-fold improvement in efficacy of immunotherapy if EphrinB2 is inhibited with a mild toxicity profile for the combination. In contrast, EV + Pembrolizumab while effective, has a significant and at times prohibitive toxicity profile. It is also unclear whether EV + Pembrolizumab can deliver the published results in patients with high EphrinB2 expression. Therefore, Cohort B is designed to explore this question.

Upon study entry, participants in either Cohort will be randomly assigned to either sEphB4-HSA + Pembrolizumab or Standard of Care (Control). Study interventions will be administered according to the protocol and participants will be monitored and assessed for safety and efficacy at designated times throughout the study.

Being tested
SEphB4-HSA, Pembrolizumab, Gemcitabine, Cisplatin, Enfortumab vedotin
Medical subject headings
Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SEphB4-HSADrug

    Also called sB4HSA

    A recombinant protein comprised of the soluble form of human receptor EphB4 fused to human serum albumin.

  • PembrolizumabDrug

    Also called Keytruda

    Antibody to human PD-1.

  • GemcitabineDrug

    Also called GEM, Gemzar

    A chemotherapy drug used to treat various types of cancer.

  • CisplatinDrug

    Also called CIS

    A type of chemotherapy drug called an alkylating agent used to treat various types of cancer.

  • Enfortumab vedotinDrug

    Also called EV, Padcev

    Nectin-4-directed antibody and microtubule inhibitor conjugate.

Study groups in NCT06493552
Study groupRoleWhat they receive
sEphB4-HSA + Pembrolizumab in MIBCExperimentalsEphB4-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).
Receives: Drug: SEphB4-HSA; Drug: Pembrolizumab
Gemcitabine-Cisplatin (GC) or Pembrolizumab Alone in MIBCActive comparatorDose 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.
Receives: Drug: Pembrolizumab; Drug: Gemcitabine; Drug: Cisplatin
sEphB4-HSA + Pembrolizumab in Naive mUCExperimentalsEphB4-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).
Receives: Drug: SEphB4-HSA; Drug: Pembrolizumab
Enfortumab Vedotin (EV) + Pembrolizumab in Naive mUCActive comparatorDose 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.
Receives: Drug: Pembrolizumab; Drug: Enfortumab vedotin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Improved pathological response (pCR) in sEphB4-HSA+Pembro vs. Standard of Care for MIBC

    Pathologic complete response (pCR), a binary outcome. pCR is defined as absence of the muscle invasive component of the tumor in the radical cystectomy specimen by pathologic review. CIS (pTis), pT1, and pTa are considered to be pCR. All patients with pCR must have pN0/M0. Patients don't have pCR due to refusal of radical cystectomy, dropout prior to radical cystectomry, or pathologic evaluation results are inconclusive or unknown will be classified as non-responders in the ITT.

    Measured: Through study completion, an average of 6 months

  2. Improved Overall Survival (OS) in sEphB4-HSA+Pembro vs. Standard of Care for MIBC

    Overall survival (OS) defined as period from randomization to death from any cause. OS will be censored at the last follow-up if patients are known to be alive. OS is a time to event variable of the primary interest.

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

  3. Improved Radiographic Objective Response Rate (ORR) in sEphB4+Pembro vs. Control in mUC

    Using RECIST 1.1 on CT or MR imaging of chest, MR imaging of Chest, Abdomen and Pelvis every 6 weeks for the first 3 months and then every 12 weeks.

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

  4. Non-inferior Overall Survival (OS) of sEphB4+Pembro vs. Control in mUC

    Overall survival (OS) defined as period from randomization to death from any cause. OS will be censored at the last follow-up if patients are known to be alive. OS is a time to event variable of the primary interest.

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Secondary outcomes (4)

  1. Improved Disease Free Survival and/or Event Free Survival in sEphB4 vs. control for MIBC arm.

    Event free survival (EFS): defined as time from randomization to any of the following events: documented disease progression precluding surgery, progression or recurrence diasease after surgery, or death due to any cause. Progresssion/recurrence will be assessed per RECIST 1.1. Patients who undego surgery with incomplete resection will be considered to have an event. Patients who start any subsequent anti-cancer therapy without a prior reported progression/recurrence will be censored at the last evaluable tumor assessment prior to initiation of the subsequent anticancer therapy. Patients who remain free of abovementioned events will be censored at the last follow-up time.

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

  2. Improved toxicity of EphB4-HSA + Pembro in MIBC vs. control

    Toxicity, as measured by the CTCAE v5.0, will be evaluated from start of study treatment to 7 days after the end of the study treatment.

    Measured: From start of study intervention until one week after cessation of study intervention, assessed up to 60 months

  3. Improved Duration of Response and/or Progression Free Survival in sEphB4 vs. control for mUC arm.

    Disease free survival is defined as the time from the date of surgery to the earlier of disease recurrence, or death from any cause. Disease recurrence includes muscle-invasive recurrences specifically in the bladder, metastatic disease outside the bladder, or death. Patients alive without documented disease recurrence will be censored at the date of last disease assessment. Measured using RECIST 1.1 on CT or MR imaging of chestMR imaging of Chest, Abdomen and Pelvis every 6 weeks for the first 3 months and then every 12 weeks.

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

  4. Improved toxicity of sEphB4-HSA + Pembro in mUC vs. control

    Toxicity, as measured by the CTCAE v5.0, will be evaluated from start of study treatment to 7 days after the end of the study treatment.

    Measured: From start of study intervention until one week after cessation of study intervention, assessed up to 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jul 2024
  2. Study start15 Mar 2025
  3. Primary completionSep 2029 (estimated)
  4. Study completionAug 2034 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
700 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06493552
Sponsor's protocol ID
B2-001
Status last verified
Mar 2025
First submitted
25 Jun 2024
Last updated
3 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing SEphB4-HSA, Pembrolizumab and Gemcitabine in people with Muscle-Invasive Bladder Carcinoma and Metastatic Urothelial Carcinoma, run by Vasgene Therapeutics, Inc at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jon Cogan, MS (323-221-7818, info@vasgene.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Improved pathological response (pCR) in sEphB4-HSA+Pembro vs. Standard of Care for MIBC (time frame: Through study completion, an average of 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06493552.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2025.

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