A study in participants with glioblastoma that has progressed after standard of care therapy, looking at the safety and effect of treatment with the experimental drug E-EDV-Dox/GC or EnGeneIC Dream Vectors (EDVs) packaged with the chemotherapy (Doxorubicin) given simultaneously with non-targeted EDVs carrying an immune enhancer called EDV-GC. (EDV-GBM Trial)

This study is testing an experimental treatment for people with a type of brain cancer called glioblastoma that has returned or progressed after the failure of standard of care therapy. The experimental treatment consists of a chemotherapy drug, Doxorubicin, packaged inside an EGFR targeted delivery vehicle to form the investigational product E-EDV-Dox. The EDV delivery vehicle is used to transport the chemotherapy directly to the brain tumor where it attaches to the surface of EGFR expressing cancer cells causing the cancer cell to die. The E-EDV-Dox are given at the same time as one other investigational product designed to boost the body's own immune system to fight the cancer. This investigational product consists of non-targeted EDVs carrying a-galactosyl ceramide or EDV-GC. The combination of these 2 drugs is known as E-EDV-Dox/GC. The study aims to evaluate the safety and efficacy of E-EDV-Dox/GC in patients with confirmed grade IV glioblastoma or high-grade glioma with features consistent with glioblastoma at time of first diagnosis. The study is designed with two phases, Phase I (dose assessment) and Phase IIa (dose expansion). In Phase I of the study a safety assessment will be performed on 6 participants, while in Phase II the recommended dosing regimen from Phase I will be open to a maximum of 40 participants. Participants in the phase IIa dose expansion part of the trial will follow the same treatment cycle visit schedule regardless of the recommended dose level. The first treatment cycle will involve bi-weekly visits for 4 weeks, followed by weekly visits for 3 weeks. Doses of E-EDV-Dox/GC in 3mL of 0.9% sodium chloride are administered intravenously over 10 seconds. The first dose of E-EDV-Dox/GC at Cycle 1 will be given at a reduced dose of 1.5 x10^9 and subsequent doses will be escalated incrementally as 2.5 x10^9, 3.75 x10^9, 4.75 x10^9, 6.0 x10^9, 7.0 x10^9 until the target dose level of 8.0 x10^9 E-EDV-Dox/GC is attained at Dose 7, Week 4. Intra-cycle dose escalation will be used for all participants in Cycle 1 only. For weeks 5-7, visits will occur once/week where 2 doses of 8.0 x10^9 E-EDV-Dox/GC will be administered 90 minutes apart during each visit. In week 8, tumour burden will be radiologically re-evaluated in accordance with Response Assessment in Neuro-Oncology (RANO 2.0) guidelines to determine treatment response. Subsequent treatment cycles will consist of weekly visits for 7 weeks where two doses will be administered at each visit 90 minutes apart. Following each 7-week treatment period is a treatment free week in which tumour burden is radiologically re-assessed (Week 8). Treatment may continue until the patient or investigator deems it suitable to stop treatment, for example if serious side effects occur or if the participants disease continues to grow. It is estimated that the study duration for participants in the active treatment phase will be approximately 6 months consisting of two weeks for screening, 16 weeks of treatment (2 cycles), depending on the disease state and tolerability to the IMP and a 30-35-day safety follow-up visit. The study will monitored to evaluate the study conduct and ensure adherence to the protocol and compliance with ICH GCP guidelines. Case Report Forms, medical records and study related material will be reviewed at regular intervals throughout the study to verify adherence to the protocol; completeness, accuracy, and consistency of the data. Any adverse events will be monitored, and ongoing safety evaluations will be conducted by a designated Safety Monitoring Board, who will assess the progress of the trial and will be responsible for decisions as whether to continue, modify, or stop the trial. This study is designed as a Phase I/IIa trial, with a 6-patient safety run in for Phase I. If greater than or equal to two of the first six evaluable patients experience a DLT the Safety Monitoring Board will review the accumulated safety data to determine whether the maximum dose applied during the study will be reduced. The committee will consist of the Principal Investigator and/or Co-Investigator(s), one independent oncologist with experience in Phase I/IIa studies, and at least one Sponsor representative. Each review will include all available data on the incidence of AEs (including SARs, DLTs, lab and vital sign data and events requiring the discontinuation of IMP) and deaths. If the Safety Monitoring Board are satisfied that the requirements for dose safety and tolerability have been met in recurrent glioblastoma, then the study will continue to enroll up to 46 participants. Participants in the Phase IIa dose expansion part of the trial will follow the same treatment cycle visit schedule regardless of the recommended dose level.