NCT06493552

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

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

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 700 (estimated)
• Sponsor: Vasgene Therapeutics, Inc · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Muscle-Invasive Bladder Carcinoma
• Metastatic Urothelial Carcinoma

Interventions

Type	Name	Description
DRUG	SEphB4-HSA	A recombinant protein comprised of the soluble form of human receptor EphB4 fused to human serum albumin.
DRUG	Pembrolizumab	Antibody to human PD-1.
DRUG	Gemcitabine	A chemotherapy drug used to treat various types of cancer.
DRUG	Cisplatin	A type of chemotherapy drug called an alkylating agent used to treat various types of cancer.
DRUG	Enfortumab vedotin	Nectin-4-directed antibody and microtubule inhibitor conjugate.

Timeline

• Start date: 2025-03-15
• Primary completion: 2029-09-01
• Completion: 2034-08-01
• First posted: 2024-07-10
• Last updated: 2025-04-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study