None listed
Conditions
Brief summary
This study aims to determine whether E-EDV-D682 in combination with the adjuvant treatment, EDV-GC is safe and effective and to identify the most responsive cancer indications (advanced EGFR-expressing solid tumors) to the E-EDV-D682/GC treatment. Who is it for? You may be eligible to join this study if you are aged 18 years and older, with an Eastern Cooperative Oncology Group (ECOG) performance score of 0-1. A life expectancy greater than 3 months, measurable disease per iRECIST criteria, adequate haematological, renal, hepatic and cardiac function. You must have positive EGFR expression on local IHC or liquid biopsy. Study details In Phase I of the study a safety assessment will be performed on 3 participants from each cancer indication. In Phase II the recommended dosing regimen from Phase I will be open to a maximum of 20 participants for each cancer indication. 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 iRECIST 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 hoped the funding from this study will help determine the safety and efficacy of EGFR targeted EDVs carrying cytotoxic drug PNU-159682 plus concurrent immunomodulatory adjuvant non-targeted EDVs carrying a-galactosyl ceramide in subjects with advanced EGFR-expressing cancers who have failed second-line therapy or where first- and/or second-line therapy is not appropriate
Interventions
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 EGF
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.
Sponsors
EnGeneIC Pty Limited
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-1. • Life expectancy of greater than or equal to 3 months. • Measurable disease per iRECIST criteria. • Adequate haematological function. • Adequate renal function as follows. • Adequate hepatic function. • Adequate cardiac function with LVEF of greater than or equal to 50% at baseline. • The subject must have positive EGFR expression on local IHC or liquid biopsy.
Exclusion criteria
• Glioblastoma. • Significant pericardial effusions, pleural effusions, or ascites. • Concurrent unstable diabetes mellitus or other contraindications for the use of corticosteroids. • Subject has experienced a history of uncontrolled coronary artery disease, with or without angina pectoris or myocardial infarction, symptomatic congestive heart failure (New York Heart Association > Class II), uncontrolled hypertension (systolic > 160 mmHg or diastolic > 100 mmHg), or cardiac arrhythmias requiring anti-arrhythmic therapy. • Clinically significant electrocardiogram (ECG) changes at enrolment which obscure the ability to assess the PR, QT, and QRS interval, congenital long QT syndrome. • Known to be human immunodeficiency virus (HIV), hepatitis B surface antigen or hepatitis C positive; or with a history of chronic active hepatitis or cirrhosis. • History of uncontrolled arterial or venous thrombosis. Subjects with a history of arterial or venous thrombosis are eligible if the subject is controlled via therapeutic intervention. • Active or uncontrolled severe infection. • Previous or current primary malignancies at other sites within last 2 years, except: In situ carcinoma of the cervix or adequately treated basal cell or squamous cell carcinoma of the skin. • Received the following procedures within 28 days prior to receiving their first dose (or has not recovered from the toxic effects of such therapy) including: other investigational therapy, radiotherapy or any major surgery. • Other therapies or procedures such as QTc interval prolonging medicines should be reviewed and where possible their use should be minimized and alternate medicines that are not QTc interval prolonging considered as substitutes. • Known allergy/hypersensitivity to investigational components or excipients (trehalose, monoclonal antibody infusions, interferon therapy, or ciprofloxacin HCl (or other quinolones). • Females who are pregnant or breastfeeding. • Subjects who cannot comply with protocol scheduled study visits or procedures, to the best of the subject and Investigator’s knowledge.
Outcome results
None listed