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Trial registered on ANZCTR


Registration number
ACTRN12625000203459
Ethics application status
Approved
Date submitted
20/01/2025
Date registered
20/02/2025
Date last updated
22/02/2025
Date data sharing statement initially provided
20/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
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)
Scientific title
An open-label, multicenter, Phase I/IIa study assessing the safety and efficacy of EGFR targeted EDVsTM 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 (EGFR EDV-D682/GC Trial)
Secondary ID [1] 313717 0
EGFR EDV-D682/GC Trial
Universal Trial Number (UTN)
Trial acronym
ENG19
Linked study record
ACTRN12619000385145 was a safety and tolerability study conducted in PDAC and Colorectal cancer patients. The current study has opened-up participation to all EGFR expressing cancer indications using the recommended phase IIa dose from ACTRN12619000385145.

Health condition
Health condition(s) or problem(s) studied:
EGFR expressing solid tumors 336313 0
Lung cancer (NSCLC and Mesothelioma) 336314 0
Bladder/Kidney cancer 336315 0
Colorectal cancer 336316 0
Triple negative breast cancer (TNBC) 336317 0
Pancreatic ductal adenocarcinoma (PDAC) 336318 0
Condition category
Condition code
Cancer 332848 332848 0 0
Bladder
Cancer 332850 332850 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 332852 332852 0 0
Breast
Cancer 332853 332853 0 0
Head and neck
Cancer 332854 332854 0 0
Kidney
Cancer 332855 332855 0 0
Lung - Mesothelioma
Cancer 332856 332856 0 0
Lung - Non small cell
Cancer 332857 332857 0 0
Malignant melanoma
Cancer 332858 332858 0 0
Pancreatic
Cancer 332859 332859 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 330316 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340383 0
To collectively assess the safety and tolerability of E-EDV-D682/GC in subjects with EGFR-expressing solid cancers
Timepoint [1] 340383 0
Vital signs and clinical pathology will be assessed prior to and at 3 hours following each dose for all participants throughout the study. All adverse events will be monitored throughout the trial and ongoing safety evaluations will be conducted by a designated safety monitoring board. For phase I participants, the primary timepoint is day 56.
Primary outcome [2] 340384 0
Evaluate overall survival (OS)
Timepoint [2] 340384 0
Survival will continue to be monitored for the duration of the long-term follow-up (every 3 months from the safety follow-up visit for the extent of participant survival).
Primary outcome [3] 340817 0
Evaluate tumor response
Timepoint [3] 340817 0
Imaging will be performed at baseline and at the completion of every cycle of treatment (every 2 months).
Secondary outcome [1] 443914 0
Objective response rate (ORR)
Timepoint [1] 443914 0
Baseline (screening) and end of each treatment cycle (week 8 and then every 8 weeks thereafter) until the participant is withdrawn from treatment
Secondary outcome [2] 443926 0
Disease control rate (DCR)
Timepoint [2] 443926 0
Baseline (screening) and at the completion of each treatment cycle (week 8), then every 8 weeks thereafter until the participant is withdrawn from treatment.
Secondary outcome [3] 443927 0
Duration of response (DOR).
Timepoint [3] 443927 0
Tumor response is assessed at the completion of each treatment cycle (week 8), then every 8 weeks thereafter until the participant is withdrawn from treatment. The duration of Response is the number of days between the first tumor response assessment of an objective response (PR or CR) to the date of the first tumor response assessment of progressive disease or death.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/03/2025
Actual
Date of last participant enrolment
Anticipated
11/01/2027
Actual
Date of last data collection
Anticipated
7/02/2028
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 27497 0
Frankston Private Hospital - Frankston
Recruitment hospital [2] 27498 0
Mater Sydney - North Sydney
Recruitment postcode(s) [1] 43608 0
3199 - Frankston
Recruitment postcode(s) [2] 43609 0
2060 - North Sydney

Funding & Sponsors
Funding source category [1] 318183 0
Commercial sector/Industry
Name [1] 318183 0
EnGeneIC Pty Limited
Country [1] 318183 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
EnGeneIC Pty Limited
Address
Country
Australia
Secondary sponsor category [1] 320587 0
None
Name [1] 320587 0
Address [1] 320587 0
Country [1] 320587 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316835 0
Bellberry Human Research Ethics Committee K
Ethics committee address [1] 316835 0
Ethics committee country [1] 316835 0
Australia
Date submitted for ethics approval [1] 316835 0
10/07/2024
Approval date [1] 316835 0
22/10/2024
Ethics approval number [1] 316835 0
2024-07-880

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 139150 0
Prof Vinod Ganju
Address 139150 0
Peninsula And Southeast Oncology Suites (PASO), Frankston Private Hospital, Suite 7, Level 3, 5 Susono Way Frankston, VIC 3199
Country 139150 0
Australia
Phone 139150 0
+61 03 9781 5244
Fax 139150 0
Email 139150 0
office@paso.com.au
Contact person for public queries
Name 139151 0
Albert Goikhman
Address 139151 0
Peninsula And Southeast Oncology Suites (PASO), Frankston Private Hospital, Suite 7, Level 3, 5 Susono Way Frankston, VIC 3199
Country 139151 0
Australia
Phone 139151 0
+61 03 9781 5244
Fax 139151 0
Email 139151 0
ag@paso.com.au
Contact person for scientific queries
Name 139152 0
Jennifer MacDiarmid
Address 139152 0
Building 53, Level 4, 11 Julius Avenue, North Ryde, Sydney, NSW 2113
Country 139152 0
Australia
Phone 139152 0
+61 02 9420 5833
Fax 139152 0
Email 139152 0
jmacdiarmid@engeneic.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
For reasons of confidentiality


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.