ofranergene obadenovec (VB-111) / NANO MRNA, VBL Therap - LARVOL DELTA

VB-111 in Surgically Accessible Recurrent/Progressive GBM (clinicaltrials.gov) - P2 | N=15 | Terminated | Sponsor: Dana-Farber Cancer Institute | Active, not recruiting ➔ Terminated; Trial stopped at request of VBL Therapeutics, as they are no longer pursuing their VB-111 development program.

Trial termination • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

VB-111 in Surgically Accessible Recurrent/Progressive GBM (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial primary completion date: Mar 2024 ➔ Aug 2024

Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

VB-111 (ofranergene obadenovec) in combination with nivolumab in patients with microsatellite stable colorectal liver metastases: a single center, single arm, phase II trial. (PubMed, J Immunother Cancer) - P2 | "In patients with MSS CLM, VB-111 and nivolumab did not improve overall response rate or survival but were tolerated with minimal toxicities. While challenging to distinguish between antiviral or antitumor, correlative studies demonstrated an immune response with activation and proliferation of CD8 T cells systemically that was poorly sustained."

Combination therapy • Journal • P2 data • Gastrointestinal Cancer • Gastrointestinal Disorder • Gene Therapies • Infectious Disease • Influenza • Liver Cancer • Oncology • Respiratory Diseases • Solid Tumor • CD8 • IL10 • TNFA

VB-111 (ofranergene obadenovec) in combination with nivolumab in patients with microsatellite stable colorectal liver metastases: a single center, single arm, phase II trial (J Immunother Cancer) - P2 | N=14 | NCT04166383 | "Median follow-up was 5.5 months. Of the 10 evaluable patients, the combination of VB-111 and nivolumab failed to demonstrate radiographic responses; at best, 2 patients had stable disease. Median overall survival was 5.5 months (95% CI: 2.3 to 10.8), and median progression-free survival was 1.8 months (95% CI: 1.4 to 1.9). The most common grade 3–4 treatment-related adverse events were fever/chills, influenza-like symptoms, and lymphopenia....In patients with MSS CLM, VB-111 and nivolumab did not improve overall response rate or survival but were tolerated with minimal toxicities."

P2 data • Colorectal Cancer

Prevalence and Prognostic Value of Non-Alcoholic Fatty Liver Disease in Patients Hospitalized With Decompensated Chronic Heart Failure. (PubMed, Kardiologiia) - "A multivariate regression analysis showed that independent predictors of NAFLD were systolic blood pressure ≥130 mm Hg (odds ratio (OR), 3.700; p <0.001), history of T2DM (OR, 2.807; p <0.005), and waist circumference >111 cm (OR, 2.530; p <0.012)...AH, T2DM, and abdominal obesity were associated with a high risk of NAFLD. However, only severe steatosis (S3) was an independent predictor of adverse clinical outcomes during a 2-year period after adjustment for known risk factors."

Journal • Addiction (Opioid and Alcohol) • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Gastroenterology • Genetic Disorders • Heart Failure • Hepatology • Hypertension • Metabolic Disorders • Myocardial Infarction • Nephrology • Non-alcoholic Fatty Liver Disease • Obesity • Pulmonary Arterial Hypertension • Renal Disease • Type 2 Diabetes Mellitus

Ofranergene Obadenovec Plus Paclitaxel Did Not Improve Survival Outcomes Among Patients With Recurrent, Platinum-Resistant Ovarian Cancer (HMP Global) - "According to Rebecca C. Arend...'Platinum-resistant ovarian cancer has a poor prognosis, [therefore we] compared the efficacy and safety of [ofranergene obadenovec] and paclitaxel with those of paclitaxel and placebo in patients with [platinum-resistant ovarian cancer].'...'The addition of [ofranergene obadenovec] to paclitaxel did not improve progression-free survival or overall survival,' concluded Dr Arend...'The negative results were unexpected in view of the phase I/II experience and the interim analysis of CA-125 response.'"

Media quote

Ofranergene obadenovec (VB-111) in combination with nivolumab in patients with microsatellite stable colorectal liver metastases: a single-center, single-arm phase II trial (SITC 2023) - "While challenging to distinguish between anti-viral or anti-tumor, correlative studies demonstrated an antigen-specific immune response with activation and proliferation of CD8+ T-cells systemically; however, this was poorly sustained and immune infiltration was sparsely seen within on-treatment tumor biopsies[5]. With its transient immunogenicity and limited clinical efficacy, a single priming dose may not be the optimal strategy for viral-mediated therapies; rather, multiple sequential doses of viral vector and earlier administration of checkpoint inhibition may be required to elicit a stronger immune response to result in tumor killing."

Clinical • Combination therapy • P2 data • Colorectal Cancer • Oncology • CD8 • IL10 • TNFA

Ofranergene Obadenovec (Ofra-Vec, VB-111) With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer: Randomized Controlled Phase III Trial (OVAL Study/GOG 3018) (J Clin Oncol) - P3 | N=408 | OVAL (NCT03398655) | Sponsor: VBL Therapeutics | "Between December 2017 and March 2022, 409 patients were randomly assigned. The median PFS was 5.29 months in the ofra-vec arm and 5.36 months in the control arm, hazard ratio (HR) 1.03 (CI, 0.83 to 1.29; P = .7823). The median OS with ofra-vec was 13.37 months versus 13.14 months, HR 0.97 (CI, 0.75 to 1.27; P = .8440). Objective response rates (ORRs) per RECIST 1.1 were similar in both arms: 28.9% with ofra-vec versus 29.6% with control. In both treatment arms, response to CA-125 was a substantial prognostic factor for both PFS and OS."

P3 data • Ovarian Cancer

Ofranergene Obadenovec (Ofra-Vec, VB-111) With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer: Randomized Controlled Phase III Trial (OVAL Study/GOG 3018). (PubMed, J Clin Oncol) - P3 | "The addition of ofra-vec to paclitaxel did not improve PFS or OS. The PFS and ORR in the control arm exceeded the results that were anticipated on the basis of the AURELIA chemotherapy control arm. CA-125 response was a substantial prognostic biomarker for PFS and OS in patients with PROC treated with paclitaxel."

Journal • P3 data • Oncology • Ovarian Cancer • Solid Tumor

VB-111 in Surgically Accessible Recurrent/Progressive GBM (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Jan 2024 ➔ Jun 2024 | Trial primary completion date: Oct 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Ofranergene Obadenovec Plus Paclitaxel Misses the Mark in Platinum-Resistant Ovarian Cancer (OncLive) - P3 | N=537 | OVAL (NCT03398655) | Sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics | "'The addition of ofra-vec to paclitaxel did not improve PFS or OS, which was unexpected in view of the phase 1/2 experience, and the interim analysis of CA-125 response,' lead study author Rebecca C. Arend...'Future studies in the platinum-resistant setting should include agents that exploit the potential synergy of targeting angiogenesis and vascular integrity in cancer.'"

Media quote • P3 data

VB-111 in Surgically Accessible Recurrent/Progressive GBM (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial primary completion date: Jun 2023 ➔ Oct 2023

Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Randomized controlled phase III trial of weekly paclitaxel ± ofranergene obadenovec (VB-111) for platinum-resistant ovarian cancer (OVAL Study/GOG 3018). (ASCO 2023) - P3 | "The addition of ofranergene obadenovec to paclitaxel did not improve PFS or OS. Clinical trial information: NCT03398655."

Clinical • P3 data • Oncology • Ovarian Cancer • Solid Tumor • EDN1 • TNFA • TNFRSF1A

Volumetric Analysis of Phase 2 and 3 Trials in Recurrent Glioblastoma Treated with VB-111 with or without Bevacizumab or Bevacizumab Monotherapy (SNO 2019) - P1/2, P3; "Patients with a radiographic response (>65% reduction) had a significant survival difference from non-responders when controlling for age, baseline tumor volume, and treatment arm (P=0.0014, HR=0.58). Responders to VB-111 monotherapy or combination therapy after priming with VB-111 exhibited characteristic, expansive areas of necrosis in areas of initial disease."

Monotherapy • P2 data • EDN1

RESULTS OF THE GLOBE STUDY: A PHASE 3, RANDOMIZED, CONTROLLED, DOUBLE-ARM, OPEN-LABEL, MULTI-CENTER STUDY OF VB-111 COMBINED WITH BEVACIZUMAB VS. BEVACIZUMAB MONOTHERAPY IN PATIENTS WITH RECURRENT GLIOBLASTOMA (SNO 2018) - "In this trial, VB-111 in combination with BEV failed to increase OS in patients with rGBM. Lack of VB-111 priming, as done in the phase II trial may explain the differences with the favorable outcomes in the latter. Patients with large progressive tumors may precluded sufficient drug exposure."

Clinical • Monotherapy • P3 data • Oncology • Solid Tumor

[VIRTUAL] Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018) (SGO 2021) - No abstract available

Clinical • Oncology • Ovarian Cancer • Solid Tumor

Ofranergene obadenovec (VB-111) an anti-cancer gene therapy induces immunotherapeutic effect in platinum resistant ovarian cancer: Histopathology findings (SGO 2019) - P1/2, P3; "Pathologic findings following VB-111 treatment suggest the induction of an Immunotherapeutic effect manifested as tumor infiltration with CD-8 T cells, and evidence of tumor necrosis. The presence of tumor-infiltrating lymphocytes is an important prognostic factor in ovarian cancer, and may contribute to the favorable survival outcome seen in the VB-111 phase II study. A pivotal phase III study evaluating the efficacy and safety of VB-111 in combination with weekly Paclitaxel compared to Paclitaxel and Placebo is currently ongoing."

Ofranergene obadenovec (VB-111) an anti-cancer gene therapy induces immunotherapeutic effect in platinum resistant ovarian cancer: Histopathology findings (SGO 2019) - P1/2, P3; "Pathologic findings following VB-111 treatment suggest the induction of an Immunotherapeutic effect manifested as tumor infiltration with CD-8 T cells, and evidence of tumor necrosis. The presence of tumor-infiltrating lymphocytes is an important prognostic factor in ovarian cancer, and may contribute to the favorable survival outcome seen in the VB-111 phase II study. A pivotal phase III study evaluating the efficacy and safety of VB-111 in combination with weekly Paclitaxel compared to Paclitaxel and Placebo is currently ongoing."

Quantitative radiographic analysis of phase II andIII trials in recurrent glioblastoma treated with VB-111 with or without bevacizumab or bevacizumab monotherapy. (ASCO 2019) - P1/2, P3; "Small recurrent tumors have a significant OS advantage when “priming” with VB-111 monotherapy prior to combination VB-111 and BV at recurrence. Patients responding to VB-111 exhibit specific imaging characteristics related to the drug mechanism of action. Clinical trial information: NCT02511405; NCT01260506"

Monotherapy • P2 data • P3 data

VB-111 in Combination With Nivolumab in People With Metastatic Colorectal Cancer (mCRC) (clinicaltrials.gov) - P2 | N=14 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • KRAS

A Study of VB-111 With Paclitaxel vs Paclitaxel for Treatment of Recurrent Platinum-Resistant Ovarian Cancer (OVAL) (clinicaltrials.gov) - P3 | N=408 | Completed | Sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Jun 2023 ➔ Jul 2022 | Trial primary completion date: Dec 2022 ➔ Jul 2022

Trial completion • Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor

VB-111 in Surgically Accessible Recurrent/Progressive GBM (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Recruiting ➔ Active, not recruiting | N=45 ➔ 15 | Trial completion date: Aug 2024 ➔ Dec 2023

Enrollment change • Enrollment closed • Trial completion date • Brain Cancer • CNS Tumor • Glioblastoma • Immunology • Oncology • Solid Tumor

A study of neo-adjuvant and adjuvant ofra-vec (VB-111) for treatment of surgically accessible recurrent GBM. (ASCO 2022) - P2 | "A previous study demonstrated a survival benefit for patients with recurrent glioblastoma (rGBM) treated with ofra-vec monotherapy, that was continued after progression in combination with bevacizumab. Other endpoints include safety and tolerability, peripheral T cell response, 6mPFS and OS. Study is open for enrolment."

Clinical • Brain Cancer • Glioblastoma • Immunology • Oncology • Solid Tumor

Treatment through progression with ofranogene obadenovec (VB-111), an anti-cancer viral therapy, significantly attenuates tumor growth in recurrent GBM: Individual phase 2 patient data. (ASCO 2017) - P1/2; "...Background: Ofranergene obadenovec (VB-111) is a viral cancer-therapy with a dual mechanism: vascular disruption and induction of a tumor directed immune response. Prolongation of overall survival (OS) has been shown in recurrent glioblastoma (rGBM) patients treated through progression with VB-111 in combination with bevacizumab (BEV) compared to historical controls and to patients with limited exposure (LE) to VB-111... Treatment through progression with VB-111 in combination with BEV induced durable tumor growth attenuation, which was associated with prolonged OS of 15 months in patients with rGBM. The GLOBE phase 3 randomized controlled trial of VB-111 in rGBM is currently underway."

Clinical • P2 data • Biosimilar • Oncology

[VIRTUAL] Validation of diffusion MRI as an imaging biomarker for bevacizumab therapy in recurrent glioblastoma in a randomized phase III trial of bevacizumab with or without VB-111 (GLOBE) (SNO 2020) - P3 | "Baseline diffusion MRI and tumor volume are independent imaging biomarkers of OS in rGBM treated with BV or BV+VB-111. Since ADCL was predictive of OS in combination BV+VB-111, results support the working hypothesis that co-administration of VB-111 with BV may block any VB-111 anti-tumor effect, whereas VB-111 monotherapy or priming may result in higher efficacy of VB-111."

Biomarker • Clinical • P3 data • Glioblastoma • Oncology • Solid Tumor • MRI