sEphB4-HSA / VasGene, National Cancer Institute - LARVOL DELTA

Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=61 | Active, not recruiting | Sponsor: University of Southern California | Terminated ➔ Active, not recruiting | Trial completion date: May 2019 ➔ Apr 2026

Enrollment closed • Trial completion date • Biliary Cancer • Cholangiocarcinoma • Gallbladder Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Multicohort Phase II Trial of sEphB4-HSA+Pembrolizumab in Solid Tumors (clinicaltrials.gov) - P2 | N=103 | Active, not recruiting | Sponsor: University of Southern California | Recruiting ➔ Active, not recruiting | N=170 ➔ 103

Enrollment change • Enrollment closed • Bladder Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

sEphB4-HSA in Treating Patients With Kaposi Sarcoma (clinicaltrials.gov) - P2 | N=23 | Completed | Sponsor: AIDS Malignancy Consortium | Active, not recruiting ➔ Completed | Trial completion date: Feb 2026 ➔ Feb 2025 | Trial primary completion date: Feb 2026 ➔ Feb 2025

Trial completion • Trial completion date • Trial primary completion date • Kaposi Sarcoma • Oncology • Sarcoma • Solid Tumor • EPHB4

sEphB4-HSA in Treating Patients With Kaposi Sarcoma (clinicaltrials.gov) - P2 | N=23 | Active, not recruiting | Sponsor: AIDS Malignancy Consortium | Trial completion date: Jun 2026 ➔ Feb 2026

Trial completion date • Kaposi Sarcoma • Oncology • Sarcoma • Solid Tumor • EPHB4

Modular Trial of sEphB4-HSA in EphrinB2-High Solid Tumors (clinicaltrials.gov) - P2/3 | N=700 | Recruiting | Sponsor: Vasgene Therapeutics, Inc | Not yet recruiting ➔ Recruiting | Initiation date: Nov 2024 ➔ Mar 2025

Enrollment open • Trial initiation date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • EPHB4

The effect of a topical curcumin formulation (VAS101) on knee pain in adults with knee osteoarthritis (ANZCTR) - P=N/A | N=60 | Recruiting | Sponsor: Clinical Research Australia | Initiation date: Feb 2025

Trial initiation date • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

P30CA014089: Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475 (clinicaltrials.gov) - P2 | N=42 | Completed | Sponsor: University of Southern California | Active, not recruiting ➔ Completed | Trial completion date: Mar 2026 ➔ Sep 2024 | Trial primary completion date: Mar 2025 ➔ Sep 2024

Trial completion • Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • BRAF • PD-1 • PD-L1 • ROS1

The effect of a topical curcumin formulation (VAS101) on knee pain in adults with knee osteoarthritis (ANZCTR) - P=N/A | N=60 | Not yet recruiting | Sponsor: Clinical Research Australia

New trial • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Novel biomarker, ephrinB2 (B2), predicts resistance to treatment and poor overall survival (OS) metastatic urothelial carcinoma (mUC) (ESMO 2024) - "Our phase II trial of sEphB4-HSA- a B2 inhibitor- plus pembrolizumab in pre-treated mUC (N=70) showed an objective response rate (ORR) of 37%...PD1/L1 Ab included pembrolizumab (n=121, 76%), atezolizumab (n=30, 19%) and nivolumab, avelumab, and durvalumab, 3%, 1%, and 1%, respectively... B2 Hi was associated with poor OS and ORR to PD1/L1 Ab monotherapy in mUC. These data propose B2-B4 pathway as a mechanism of resistance to PD1/L1 Ab, a biomarker of outcome, and a therapeutic target."

Biomarker • Clinical • IO biomarker • Metastases • Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer • EPHB4

Improved efficacy of pembrolizumab combined with soluble EphB4-albumin in HPV-negative EphrinB2 positive head neck squamous cell carcinoma. (PubMed, Oncotarget) - "The combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC."

Journal • Cardiovascular • Fatigue • Head and Neck Cancer • Hypertension • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EPHB4

Combination of sEphB4-HSA and pembrolizumab shows promise in HPV-negative EphrinB2 positive HNSCC (News-Medical) - P2a | N=42 | NCT03049618 | "In this new study, researchers...conducted a phase II single-arm clinical trial of locally advanced or metastatic HNSCC patients treated with a combination of soluble EphB4-human serum albumin (sEphB4-HSA) fusion protein and pembrolizumab after platinum-based chemotherapy with up to 2 prior lines of treatment...Twenty-five patients were enrolled. Median follow up was 40.4 months (range 9.8 – 40.4). There were 6 responders (ORR 24%). There were 5 responders in the 11 HPV-negative and EphrinB2 positive patients, (ORR 45%) with 2 of these patients achieving a complete response (CR). The median PFS in HPV-negative/EphrinB2 positive patients was 3.2 months (95% CI 1.1, 7.3). Median OS in HPV-negative/EphrinB2 positive patients was 10.9 months (95% CI 2.0, 13.7)...The combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC."

P2a data • Squamous Cell Carcinoma of Head and Neck

Modular Trial of sEphB4-HSA in EphrinB2-High Solid Tumors (clinicaltrials.gov) - P2/3 | N=700 | Not yet recruiting | Sponsor: Vasgene Therapeutics, Inc

IO biomarker • New P2/3 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

sEphB4-HSA in Treating Patients With Kaposi Sarcoma (clinicaltrials.gov) - P2 | N=23 | Active, not recruiting | Sponsor: AIDS Malignancy Consortium | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2024 ➔ Jun 2026 | Trial primary completion date: Mar 2024 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date • Kaposi Sarcoma • Oncology • Sarcoma • Solid Tumor

Association of ephrinB2 (B2) expression on overall survival (OS) and resistance to PD1/L1 inhibitors (inh) in metastatic urothelial carcinoma (mUC). (ASCO 2024) - "Our phase II trial of sEphB4-HSA, a B2 inhibitor, combined with pembrolizumab in pre-treated mUC (N=70) showed an objective response rate (ORR) of 37%...PD1/L1 inh included pembrolizumab (n = 111, 78%), atezolizumab (n = 25, 17%), nivolumab, avelumab, and durvalumab in 3%, 1%, and 1%, respectively... B2 Hi is associated with poor OS and poor ORR in PD1/L1 inh monotherapy treated mUC acting as a biomarker of disease outcome. These data suggest B2-B4 pathway to be a mechanism of resistance to PD1/L1 inh and a therapeutic target."

Clinical • IO biomarker • Metastases • Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer • EPHB4

P30CA014089: Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475 (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: University of Southern California | Phase classification: P2a ➔ P2 | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2024 ➔ Mar 2025

Combination therapy • IO biomarker • Phase classification • Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • BRAF • PD-1 • PD-L1 • ROS1

Multicohort Phase II Trial of sEphB4-HSA+Pembrolizumab in Solid Tumors (clinicaltrials.gov) - P2 | N=170 | Recruiting | Sponsor: University of Southern California | Trial completion date: Nov 2024 ➔ Nov 2026 | Trial primary completion date: Nov 2023 ➔ Nov 2025

Combination therapy • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=61 | Terminated | Sponsor: University of Southern California | Active, not recruiting ➔ Terminated; Lack of funding

Combination therapy • Metastases • Trial termination • Biliary Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

sEphB4-HSA in Treating Participants With BCG-Unresponsive or Refractory Bladder Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: University of Southern California | N=36 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

EphrinB2 (B2) expression predicts poor response to PD1/L1 antibodies (Ab) in metastatic urothelial carcinoma (mUC). (ASCO 2023) - "Our phase II trial of sEphB4-HSA (JCO PMID 35984996) which targets B2, in combination with pembrolizumab in previously treated mUC (N=70) demonstrated an objective response rate (ORR) of 37%...PD1/L1 Ab were administered in the post-platinum progressive disease (n=95, 79%) and first-line setting (n=25, 21%) and included pembrolizumab (n=88, 73%), atezolizumab (n=26, 22%) and nivolumab, avelumab, and durvalumab, 3%, 1%, and 1%, respectively... In addition to conferring poor prognosis in MIBC, B2 expression is associated with poor ORR to PD1/L1 Ab monotherapy in mUC. Given that the combination of B2 inhibition & pembrolizumab was more active in B2 expressing mUC, these data provide further rationale for investigating B2 as a mechanism of resistance to PD1/L1 ab, biomarker of response and a therapeutic target. >"

IO biomarker • Metastases • Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer • EPHB4

sEphB4-HSA in Treating Participants With BCG-Unresponsive or Refractory Bladder Cancer (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: University of Southern California | Trial completion date: Apr 2025 ➔ Aug 2025 | Trial primary completion date: Apr 2024 ➔ Aug 2024

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

EphrinB2 Inhibition and Pembrolizumab in Metastatic Urothelial Carcinoma. (PubMed, J Clin Oncol) - "The combination of sEphB4-HSA and pembrolizumab appears synergistic with improved OS and ORR compared with historical data for programmed death 1/programmed death ligand 1 monotherapy."

Journal • Oncology • Solid Tumor • Urothelial Cancer • EPHB4 • PD-L1

A phase II study of sEphB4-HSA in metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2020) - P2; " Eligibility criteria include mCRPC with disease progression after second generation AR targeted therapy (i.e., abiraterone or enzalutamide), ECOG PS ≤ 2, and adequate renal, hepatic and hematological functions. Clinical trial information: NCT04033432. Research Funding: U.S. National Institutes of Health, Pharmaceutical/Biotech Company."

P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • EPHB4 • PTEN

sEphB4-HSA in Treating Participants With BCG-Unresponsive or Refractory Bladder Cancer (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: University of Southern California | Trial completion date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Dec 2023 ➔ Apr 2024

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

sEphB4-HSA With RT+Chemo or Cetux in Patients With Intermediate to High Risk LAHNSCC (clinicaltrials.gov) - P1 | N=3 | Completed | Sponsor: University of Colorado, Denver | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

P30CA014089: Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475 (clinicaltrials.gov) - P2a | N=42 | Active, not recruiting | Sponsor: University of Southern California | Trial completion date: Mar 2024 ➔ Mar 2025 | Trial primary completion date: Mar 2023 ➔ Mar 2024

Combination therapy • IO biomarker • Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • BRAF • PD-L1 • ROS1