Phase Ib Clinical Trial of IGV-001 for Patients with Newly Diagnosed Glioblastoma

Abstract

This study extends the previous findings of a systemic treatment effect of a unique combination product, IGV-001, in recurrent GBM. As an autologous tumor cell treatment, results were postulated to be an immune response. This follow-on phase Ib trial for newly diagnosed GBM was designed to further test this hypothesis with broad entry criteria. While the primary objective remained safety, unexpected clinical and radiographic responses prompted termination of randomization and accrual only to the highest exposure cohort after patient 23. The protocol amendment also elevated analysis of clinical endpoints from exploratory objectives to clinical endpoint assessments joining the established radiographic assessments. The results of this trial reflect compelling improvement in PFS in the ITT population and for PFS, OS and PFS MGMT methylated subgroups who would have met entry criteria for current phase 3 newly-diagnosed GBM trials. These clinical endpoint improvements were accompanied by striking radiographic improvements with sustained meaningful quality of life.

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

“…Previously, the ground-breaking application of EVs in anti-tumor immunotherapy ( Zitvogel et al, 1998 ) led to two clinical trials where EVs activated patient immune response against tumor antigens ( Escudier et al, 2005 ; Morse et al, 2005 ). Since then, refinements in EV production and modification have led to successful reduction in tumor size in various pre-clinical models ( Lee et al, 2012 ; Mahaweni et al, 2013 ; Rao et al, 2016 ; Cheng et al, 2021 ) and additional clinical trials exploiting their immunomodulatory capabilities to target various cancer types (NCT01550523, NCT01159288, and NCT02507583) ( Besse et al, 2016 ; Andrews et al, 2021 ). The use of EVs as antigen vehicles is an approach still under development ( Cheng et al, 2021 ; Hu S. et al, 2021 ), but does represent the most successful translated application.…”

“…Due to their nanoscale size, stability, biocompatibility, and propensity for cellular uptake, EVs have been recognized as viable vehicles for therapeutic application. Recent studies have highlighted the therapeutic potential of EVs, investigated in clinical trials (phase I/II) for their regenerative capacity (NCT04223622) ( Niada et al, 2019 ), vaccine potential ( Gehrmann et al, 2014 ; Narita et al, 2015 ; Besse et al, 2016 ; Coakley et al, 2017 ; Shehata et al, 2019 ; Nikfarjam et al, 2020 ; Andrews et al, 2021 ), immunotherapeutic activity ( Narita et al, 2015 ; Besse et al, 2016 ; Chen G. et al, 2018 ), and application as delivery vectors (NCT01294072). Indeed, pre-clinical and therapeutic applications of EVs across a wide range of pathologies for tissue repair and regeneration are well underway ( Table 1 ).…”

Extracellular vesicles: mediators of intercellular communication in tissue injury and disease

“…Furthermore, a phase I clinical trial is investigating the use of an antisense oligodeoxynucleotide against insulin-like growth factor type I for treatment of malignant gliomas. The antisense molecule, released from a small implanted diffusion chamber that induces apoptotic cell death in surrounding tumor cells, is hypothesized to work together with tumor-associated antigen carrying EVs released from apoptotic cells to stimulate an anti-tumor immune response in the TME [ 128 ].…”

The future of cancer immunotherapy for brain tumors: a collaborative workshop

“…These clinical endpoint improvements were accompanied by striking radiographic improvements with sustained meaningful quality of life. [ 34 ].…”