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 pancreatic and other cancers whose disease has progressed after one or two treatment regimes, or where other standard therapies are not appropriate.
A Phase I/IIa Study of EGFR-Targeted EDVTMs Carrying the Cytotoxic Drug PNU-159682 (E-EDV-D682) with Concurrent Immunomodulatory Adjuvant Non-Targeted EDVs carrying an immunomodulator (EDV-GC) in (i) Cohort 1, Subjects with Advanced Pancreatic Cancer and (ii) Cohort 2, Subjects with other EGFR Expressing Solid Tumours, who have Failed First or Second-line Therapy or where other Standard Therapies are not Appropriate.
EnGeneIC Pty Limited
80 participants
Mar 4, 2019
Interventional
Conditions
Summary
The primary purpose of this trial is to evaluate the safety and efficacy of a combination treatment consisting of EDV's packaged with a chemotherapeutic targeted to cancer cells and an adjuvant therapy that is designed to boost the bodies own immune system to fight the cancer. In Phase I the study will enrol 5 evaluable patients per cohort. In Phase IIa the study, will enrol up to an additional 35 evaluable patients per cohort. Therefore up to 40 evaluable subjects per cohort will be enrolled in the study. Who is it for? You may be eligible to enrol in this trial if you are aged 18 years old or older and have either advanced pancreatic cancer or any solid tumour that has been treated with at least one prior treatment regime or where other standard therapies are not appropriate. Study details All participants enrolled in this trial will receive combination treatment with the following: 1. The EnGeneIC Dream Vector(TM) (EDV(TM)). The EDVs are very small particles known as nanocells, which are made from Salmonella bacteria. The type of Salmonella is one that does not cause disease. The EDV is the delivery vehicle used to transport the study drug directly to the site of the cancer. 2. The Cancer Treatment. The study drug is a type of chemotherapy. The study drug is packaged inside the EDVs (E-EDV-D682) and is targeted directly to the site of the tumour, rather than the body’s healthy cells and tissues. The EDVs will also be packaged with another substance that is designed to boost the immune system, called EDV-GC. 3. Bispecific antibody. The EDV delivery system works in 2 ways, as well as carrying the study drug, the EDV surface is also coated with a bispecific antibody. A bispecific antibody is two antibodies linked together, such that one can attach to the EDV and the other to cancer cells. Once attached, the EDVs are taken up inside the cancer cells, and the study drug is delivered directly inside the cell itself, causing the cancer cell to die. Treatment will be administered in 5-week cycles. The treatments are prepared in a syringe and administered into a vein (intravenous), over a period of 20 minutes using a special pump. Two doses of the treatment are given twice per week for the first 2 weeks, followed by weekly treatment for a further two weeks, with a treatment free week where a CT or MRI scanning is performed to evaluate the tumours response to treatment (Week 5). Treatment may continue until the patient or investigator deems it suitable to stop treatment, for example if serious side effects occur or if the patients disease continues to grow. It is hoped that the findings from this trial will provide information on whether E-EDV-D682 and EDV-GC treatment may be safe and effective for the treatment of otherwise incurable pancreatic and other advanced solid tumours.
Eligibility
Inclusion Criteria12
- Eastern Cooperative Oncology Group (ECOG) performance score of 0-1.
- Life expectancy greater than or equal to 3 months
- Histologically or cytologically confirmed pancreatic cancer or other solid tumours known to express EGFR including, but not limited to, kidney cancer (renal cell adenocarcinoma), melanoma, bladder cancer, colorectal cancer, non-small cell lung cancer (NSCLC) and head and neck cancer.
- Measurable disease per iRECIST criteria.
- Must be able to undergo CT or MRI (+/- PET) evaluation.
- Available archived primary or metastatic neoplastic tumour tissue available for EGFR expression staining.
- Adequate haematological function.
- Adequate renal function
- Adequate hepatic function
- Adequate cardiac function with LVEF greater than or equal to 50% at baseline.
- Serum phosphate levels within normal range (2.1-4.1 mg/dL) at baseline.
- Cortisol levels within normal range, in accordance with hospital accredited laboratory reference range.
Exclusion Criteria20
- 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 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 on low dose molecular weight heparins or low dose aspirin.
- Active or uncontrolled severe infection.
- Previous or current primary malignancies at other sites within last 2 years, except:
- In situ carcinoma of the cervix.
- 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
- any major surgery.
- Prior other therapies or procedures prior to receiving their first dose:
- Anticoagulation therapy (within 7 days of Study Day 1), except low molecular weight heparins or low dose aspirin.
- 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).
- Female who is pregnant or breastfeeding.
- Subject who cannot comply with protocol scheduled study visits or procedures, to the best of the subject and Investigator’s knowledge.
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
This is an open-label, Phase I/IIa study of EGFR-targeted EDVs containing the cytotoxic drug PNU-159682 (E-EDV-D682), which is administered intravenously (IV) in combination with immunomodulatory EDV-GC in subjects with advanced pancreatic cancer and other EGFR expressing solid tumours who have failed first or second line therapy, or where other standard therapies are not appropriate. The Phase I component of the study will enrol 5 patients per cohort (5 patients with advanced pancreatic and 5 patients with other EGFR expressing solid tumours), to evaluate the safety and tolerability of the combination of E-EDV-D682 with adjuvant EDV-GC. The first treatment cycle for both cohorts (pancreatic patients and participants with other solid tumours), is identical and will comprise of two doses administered 30 minutes apart, the first a combination E-EDV-D682/GC followed by a dose of single agent E-EDV-D682. The 2 doses will be given twice per week for the first 2 weeks (8 doses). After which E-EDV-D682/GC and E-EDV-D682, will be administered weekly for 2 further weeks (4 doses) (12 doses over 4 weeks). Week 5 is treatment free, but tumour burden will be radiologically re-evaluated in accordance with iRECIST to determine treatment response. Subsequent cycles will follow a weekly dosing schedule, where the same 2 doses, E-EDV-D682/GC followed 30 minutes after completion by E-EDV-D682, will be administered weekly for 4 weeks (8 doses). Following each 4-week treatment period is a treatment free week in which tumour burden is radiologically re-assessed (Week 5). In order to foster tolerance & minimise potential infusion related reactions, the first dose of combination E-EDV-D682/GC at Cycle 1, will be given at a reduced dose level of 2.5 x 10^9. Subsequent doses (Doses 3, 5, 7, 9 and 11) will then be escalated incrementally until the target dose level, 8 x 10^9, is attained at Cycle 1, Dose 11. Single agent E-EDV-D682 will commence at a starting dose of 2 x 10^9 at Cycle 1, Dose 2, escalating to a maximum dose level of 7 x 10^9 by Cycle 1, Dose 12. All subsequent cycles of both the combination and E-EDV-D682 alone will be administered at the maximum dose levels attained in Cycle 1. Participants may continue to receive investigational medicinal product whilst they continue to derive clinical benefit with no prohibitive toxicity, or until the subject becomes intolerant to the study medication, the subject withdraws consent, or at the discretion of the Investigator if it is felt to be in the best interests of the participant to withdraw. Post-review by the Safety Monitoring Board and authorization by said committee, the Phase IIa component (dose expansion) will open to enrolment. Up to an additional 35 patients/cohort will be recruited to further evaluate the safety and anti-tumour efficacy of the combination of E-EDV-D682 and EDV-GC (E-EDV-D682/GC) as per the schedule outlined.
Locations(2)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12619000385145