A study of EnGeneIC Dream Vectors (EDV's) packaged with the chemotherapy, E-EDV-D682 given simultaneously as non-targeted EDVs carrying an immune enhancer called EDV-GC, in participants with advanced epidermal growth factor expressing cancers whose disease has progressed after one or two treatment regimes, or where other standard therapies are not appropriate. (EGFR EDV-D682/GC Trial)

This study is testing an experimental treatment for people with advanced cancer after the failure of first or second line therapy or for people who do not have other treatment options. The experimental treatment consists of a chemotherapy drug, PNU-159682 packaged inside an EGFR targeted delivery vehicle to form the investigational product E-EDV-D682. The EDV delivery vehicle is used to transport the chemotherapy directly to the tumor via the blood stream where it attaches to the surface of EGFR expressing cancer cells causing the cancer cell to die. The E-EDV-D682 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-D682/GC. The study aims to evaluate the safety and efficacy of E-EDV-D682/GC in patients with EGFR-expressing solid tumors. 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 3 participants from each of the following cancer indications: Lung cancer (NSCLC and Mesothelioma), Bladder/Kidney cancer, Colorectal cancer, Triple negative breast cancer (TNBC), Pancreatic ductal adenocarcinoma (PDAC) and other EGFR expressing solid tumors such as Head and Neck cancer, Malignant melanoma and Neuroendocrine tumors. In Phase II the recommended dosing regimen from Phase I will be open to a maximum of 20 participants for each cancer indication. 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 7 weeks. Doses of E-EDV-D682/GC in 3mL of 0.9% sodium chloride are administered intravenously over 10 seconds. In week 8, tumour burden will be radiologically re-evaluated in accordance with immune Response Evaluation Criteria in Solid Tumours (iRECIST) guidelines to determine treatment response. Subsequent cycles will consist of weekly visits for 7 weeks. 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 4-5 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. All AEs 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 3-patient run in (Phase I) for each tumor indication. The Safety Monitoring Board will review the accumulated safety data after the first three evaluable patients have completed one cycle of EDV treatment. 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. Alternative or additional dosing regimens may be explored based on emerging safety data from any part of the study. Phase IIa will start after 3 participants from each cancer indication have completed their dose limiting toxicity evaluation period (Days 1-56) and the safety committee has met to review the safety data. 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.