Phase I study of VSV-GP (BI 1831169) as monotherapy or combined with ezabenlimab in advanced and refractory solid tumors
The latest Clinical Trial Protocol published in our partner journal Future Oncology describes the first-in-human, Phase I, dose-escalation study of VSV-GP alone (part 1) and in combination (part 2) with the immune checkpoint inhibitor, ezabenlimab, in patients with advanced, metastatic or relapsed and refractory solid tumors. Read the full paper here
VSV-GP is a type of oncolytic virus that has effectively destroyed cancer cells in preclinical studies. The primary objectives of part 1 are to determine the maximum tolerated dose and/or the recommended monotherapy Phase II dose, and to assess the safety, tolerability and early efficacy of VSV-GP when administered via IT, IV and combined IT and IV routes. The primary objectives of part 2 are to determine the maximum tolerated dose and/or the recommended combination therapy phase II dose, and to assess the safety and tolerability of VSV-GP (administered IT, IV and both) in combination with ezabenlimab. The results from this ongoing study will help inform the development of VSV-GP.
Abstract
Patients with advanced, recurrent or metastatic cancer have poor prognosis despite treatment advancements. Vesicular stomatitis virus (VSV)-GP (BI 1831169) is a chimeric VSV with its neurotropic glycoprotein G replaced by the non-neurotropic glycoprotein (GP) of the lymphocytic choriomeningitis virus. This live, recombinant oncolytic virus has demonstrated preclinical efficacy as a viral-based immunotherapy due to its interferon-dependent tumor specificity, potent oncolysis and stimulation of antitumor immune activity. Co-administration of the immune checkpoint inhibitor, ezabenlimab (BI 754091), alongside VSV-GP may synergistically enhance antitumor immune activity. Here, we describe the rationale and design of the first-in-human, Phase I, dose-escalation study of VSV-GP alone and in combination with the immune checkpoint inhibitor ezabenlimab in patients with advanced, metastatic or relapsed and refractory solid tumors (NCT05155332).
Plain language summary
There is a need to develop new treatments for people living with cancer. Immunotherapy is a type of medicine that works by helping the body’s natural defenses, known as the immune system, to destroy cancer cells. There are different types of immunotherapies such as oncolytic viruses (OVs) and immune checkpoint inhibitors (ICIs). OVs are viruses that may help destroy cancer cells while leaving normal cells unharmed. They work by replicating within cancer cells; this causes them to burst and release more of the virus which then infects nearby cancer cells and activates the body’s immune system. ICIs may be able to work together with OVs to amplify this effect. VSV-GP is a type of OV that has been shown to effectively destroy cancer cells in animal studies. This first-in-human study will investigate VSV-GP on its own and in combination with an ICI called ezabenlimab for the treatment of late-stage cancer or cancer that has spread to multiple parts of the body. Here, we describe the background and design of this study in progress which aims to find out if VSV-GP alone or in combination with ezabenlimab is effective against cancer, the suitable dose and if any side effects occur.