Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: results of a phase I/II study
| Autor: | Timothy F. Cloughesy, Laurence S. Freedman, Felix Bokstein, Benjamin M. Ellingson, Andrew Brenner, Katherine B. Peters, Naamit Sher, Eyal Breitbart, Shlomit Yust-Katz, Patrick Y. Wen, Itzhak Mendel, Bernice Oberman, Idit Peretz, Tamar Rachmilewitz Minei, Niva Yakov, James J. Vredenburgh, Deborah T. Blumenthal, Yael C Cohen, Noa Lowenton-Spier |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Bevacizumab Oncology and Carcinogenesis Clinical Investigations law.invention Rare Diseases Randomized controlled trial law Clinical Research Internal medicine Antineoplastic Combined Chemotherapy Protocols Clinical endpoint AcademicSubjects/MED00300 Medicine Humans Progression-free survival Oncology & Carcinogenesis Adverse effect 6.2 Cellular and gene therapies Cancer business.industry Surrogate endpoint Brain Neoplasms Hazard ratio glioblastoma Neurosciences Genetic Therapy gene therapy Progression-Free Survival viral immuno-oncology Orphan Drug Tolerability 6.1 Pharmaceuticals VB-111 AcademicSubjects/MED00310 anti-angiogenesis Neurology (clinical) business medicine.drug |
| Zdroj: | Neuro-oncology, vol 22, iss 5 Neuro-Oncology |
| Popis: | Background VB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM). Methods Patients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS). Results VB-111 was well tolerated. The most common adverse event was transient mild-moderate fever. Median OS time was significantly longer in the primed combination group compared with both LE (414 vs 223 days; hazard ratio [HR], 0.48; P = 0.043) and unprimed combination (414 vs 141.5 days; HR, 0.24; P = 0.0056). Patients in the combination phase of the primed combination group had a median PFS time of 90 days compared with 60 in the LE group (HR, 0.36; P = 0.032), and 63 in the unprimed combination group (P = 0.72). Radiographic responders to VB-111 exhibited characteristic, expansive areas of necrosis in the areas of initial enhancing disease. Conclusions Patients with rGBM who were primed with VB-111 monotherapy that continued after progression with the addition of bevacizumab showed significant survival and PFS advantage, as well as specific imaging characteristics related to VB-111 mechanism of action. These results warrant further assessment in a randomized controlled study. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|