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

NCT06493552 | Recruiting Phase 2 FDA Drug

• 1 other identifier: B2-001
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Muscle-Invasive Bladder Carcinoma; Metastatic Urothelial Carcinoma

Outcome Measures

Primary Outcomes (4)

• 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.

  Through study completion, an average of 6 months

• 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.

  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

• 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.

  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

• 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.

  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)

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

  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

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

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

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

  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

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

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

Study Arms (4)

sEphB4-HSA + Pembrolizumab in MIBC

EXPERIMENTAL

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).

Drug: SEphB4-HSA; Drug: Pembrolizumab

Gemcitabine-Cisplatin (GC) or Pembrolizumab Alone in MIBC

ACTIVE COMPARATOR

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.

Drug: Pembrolizumab; Drug: Gemcitabine; Drug: Cisplatin

sEphB4-HSA + Pembrolizumab in Naive mUC

EXPERIMENTAL

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).

Drug: SEphB4-HSA; Drug: Pembrolizumab

Enfortumab Vedotin (EV) + Pembrolizumab in Naive mUC

ACTIVE COMPARATOR

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.

Drug: Pembrolizumab; Drug: Enfortumab vedotin

Interventions

SEphB4-HSA DRUG

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

Also known as: sB4HSA

sEphB4-HSA + Pembrolizumab in MIBC; sEphB4-HSA + Pembrolizumab in Naive mUC

Pembrolizumab DRUG

Antibody to human PD-1.

Also known as: Keytruda

Enfortumab Vedotin (EV) + Pembrolizumab in Naive mUC; Gemcitabine-Cisplatin (GC) or Pembrolizumab Alone in MIBC; sEphB4-HSA + Pembrolizumab in MIBC; sEphB4-HSA + Pembrolizumab in Naive mUC

Gemcitabine DRUG

A chemotherapy drug used to treat various types of cancer.

Also known as: GEM, Gemzar

Gemcitabine-Cisplatin (GC) or Pembrolizumab Alone in MIBC

Cisplatin DRUG

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

Also known as: CIS

Gemcitabine-Cisplatin (GC) or Pembrolizumab Alone in MIBC

Enfortumab vedotin DRUG

Nectin-4-directed antibody and microtubule inhibitor conjugate.

Also known as: EV, Padcev

Enfortumab Vedotin (EV) + Pembrolizumab in Naive mUC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• o NOTE: Contraception should be continued using two highly effective methods for a period of 120 days after the last dose of treatment.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vasgene Therapeutics, Inc: lead

Study Sites (1)

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

pembrolizumab; Gemcitabine; Cisplatin; enfortumab vedotin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Sarmad Sadeghi, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jon Cogan, MS

CONTACT

323-221-7818; info@vasgene.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2024
• First Posted: July 10, 2024
• Study Start: March 15, 2025
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): August 1, 2034
• Last Updated: April 3, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)