A study of EnGeneIC Dream Vectors (EDV's) packaged with the chemotherapy PNU-159682, given simultaneously as non-targeted EDVs carrying an immune enhancer called EDV-60mer, in participants with advanced cancer who have no curative treatment options. .
A Phase 1 Study of Anti-Human EGFR (Vectibix Sequence) Targeted EDVTMs Carrying the Cytotoxic Drug PNU-159682 (EGFR(V)-EDV-PNU) with Concurrent Non-Targeted EDVs Carrying an Immunomodulatory Adjuvant (EDV-60mer) in Subjects with Advanced Solid Tumours who have No Curative Treatment Options
EnGeneIC Pty Limited
20 participants
May 19, 2017
Interventional
Conditions
Summary
The primary purpose of this trial is to evaluate the safety and efficacy of a combination treatment of EnGeneIC Dream Vectors (EDV's) packaged with the chemotherapy PNU-159682, given with adjuvant EDV-60mer. Who is it for? You may be eligible to enroll in this trial if you are aged 18 to 75 years old and have an advanced solid tumour that is metastatic or unresectable which cannot be treated with standard care or for which standard care treatment is no longer effective. 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 called PNU-159682. PNU-159682 is a type of chemotherapy. The study drug is packaged inside the EDVs (EGFR(V)-EDV-PNU) and is delivered 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-60mer. 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 8-week cycles. The treatment is combined in a syringe and administered in to a vein (intravenous), over a period of 20 minutes using a special pump. One dose of the treatment is given each week for the first 7 weeks, followed by a treatment free week where a CT or MRI scanning is performed to evaluate the tumours response to treatment (Week 8). Treatment will continue for up to 12 months or 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. Each participant will receive one of two possible dose levels, depending on when they are enrolled and on the drug effects in previous participants. It is hoped that the findings from this trial will provide information on whether EGFR(V)-EDV-PNU and EDV-60mer treatment may be safe and effective for the treatment of otherwise incurable advanced solid tumours.
Eligibility
Inclusion Criteria7
- Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
- Life expectancy greater than 3 months
- Histologically or cytologically confirmed advanced solid tumour that is metastatic or unresectable and for which standard curative or palliative measures are not available or are no longer effective.
- Measurable disease per iRECIST criteria.
- Able to undergo CT or MRI (+/- PET) evaluation as applicable to tumour type.
- Available archived primary or metastatic neoplastic tumour tissue available for EGFR expression staining, if not already performed as standard of care.
- Adequate cardiac function with LVEF greater or equal to 50% at baseline.
Exclusion Criteria20
- Significant pericardial effusions, pleural effusions or ascites.
- Concurrent unstable diabetes mellitus or other contraindications for the use of dexamethasone.
- Uncontrolled concurrent cardiac disease including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.
- 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.
- Uncontrolled brain metastases. Subjects with a history of brain metastases are eligible if the subject is stable and off corticosteroids for at least 2 weeks prior to treatment in the study. PAtients who have undergone glucocorticoid tapering but who have not tolerated complete withdrawal and still require a nominal maintenance dose, will be reviewed on a case by case basis.
- 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 therapies or procedures within 28 days prior to Cycle 1, Dose 1 (or has not recovered from the toxic effects of such therapy) including:
- Therapy with an EGFR inhibitor e.g. cetuximab or erlotinib
- Anti-angiogenic therapy e.g. Bevacizumab (Avastin)
- Immunotherapeutic agents, vaccines, or monoclonal antibody therapy
- Alkylating agents
- Chemotherapy
- Radiotherapy with the exception of palliative radiotherapy
- Other investigational therapy.
- Any major surgery.
- Prior exposure to PNU.
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Interventions
This is an open-label feasibility study of Epidermal Growth Factor Receptor (EGFR)(V)-EDVs containing PNU-159682 administered via intravenous (IV) infusion in combination with EDVs containing an immunomodulatory adjuvant (EDV-60mer), in subjects with advanced solid tumours who have no curative treatment options. EGFR(V)-EDV-PNU and EDV-60mer will be mixed together and administered intravenously in cycles consisting of weekly infusions for 7 weeks (7 doses), followed by a treatment free week in which tumours are assessed radiologically (week 8). Two dose levels will be explored according to standard 3+3 dose escalation guidelines. The first dose level of EGFR(V)-EDV-PNU will be 2.5 x 10^9. The starting dose of EDV-60mer will be 5 x 10^8, EGFR(V)-EDV-PNU will be gradually escalated from dose 1 of the first treatment cycle to reach the required maximum dose level. Intra-cycle dose escalation is intended to build treatment toleration. The second dose level will be 5 x 10^9 of EGFR(V)-EDV-PNU, the concurrent dose of EDV-60mer will be 2 x 10^9, On determination of the recommended phase two dose (RP2D), additional participants will be enrolled at this dose level up to a total of 20 for the whole study. If both dose levels are deemed safe, then the highest dose level administered will be the RP2D (i.e. Dose Level 2 with 5 x 109 EGFR(V)-EDV-PNU and 2 x 109 EDV-60mer). A participant may continue EGFR(V)-EDV-PNU with concurrent adjuvant EDV-60mer treatment as long as their disease is responding or remains stable, the participant does not experience any unacceptable toxicity or withdraws consent or at the discretion of the Investigator withdrawal is felt to be in the best interests of the participant.
Locations(2)
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ACTRN12617000037303