RECRUITING

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

Conditions

Muscle-Invasive Bladder Carcinoma Metastatic Urothelial Carcinoma

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2025-03-15

Study Completion:2034-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06493552

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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. * 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. * 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 * 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. * 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	* 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. * 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.

Inclusion Criteria

Exclusion Criteria

* 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.
* 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.
* 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
* 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.
* 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

* 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.
* 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.

Contacts and Locations

Study Contact

Jon Cogan, MS

CONTACT

323-221-7818

info@vasgene.com

Principal Investigator

Sarmad Sadeghi, MD

PRINCIPAL_INVESTIGATOR

University of Southern California

Study Locations (Sites)

Sarcoma Oncology Center

Santa Monica, California, 90403

United States

Collaborators and Investigators

Sponsor: Vasgene Therapeutics, Inc

Sarmad Sadeghi, MD, PRINCIPAL_INVESTIGATOR, University of Southern California

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-03-15

Study Completion Date2034-08

Study Record Updates

Study Start Date2025-03-15

Study Completion Date2034-08

Terms related to this study

Additional Relevant MeSH Terms

Muscle-Invasive Bladder Carcinoma
Metastatic Urothelial Carcinoma