Modular Trial of sEphB4-HSA in EphrinB2-High Solid Tumors
NCT Number: NCT06493552
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2|PHASE3
Conditions: Muscle-Invasive Bladder Carcinoma|Metastatic Urothelial Carcinoma
Interventions: DRUG: SEphB4-HSA|DRUG: Pembrolizumab|DRUG: Gemcitabine|DRUG: Cisplatin|DRUG: Enfortumab vedotin
Sponsor: Vasgene Therapeutics, Inc
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 700
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2034-08

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.

Primary Outcome Measures: 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 Outcome Measures: 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., 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, 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., 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., 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., 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, 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., From start of study intervention until one week after cessation of study intervention, assessed up to 60 months