412TiP - The Tailored EDVTM trial: A phase I feasibility study evaluating EGFR-targeted EDVTM nanocells as a therapy platform in patients with refractory ad...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Clinical research
Basic Scientific Principles
Presenter Stephen Clarke
Citation Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368
Authors S. Clarke1, S. Sidhu2, N. Pavlakis3, H. Brahmbhatt4, J. Macdiarmid5
  • 1Northern Cancer Institute, University of Sydney, 2065 - Sydney/AU
  • 2Endocrine Surgery Unit, University of Sydney, Sydney/AU
  • 3Northern Cancer Institute, University of Sydney, Sydney/AU
  • 4Biotechnology, EnGeneIC, 2066 - Sydney/AU
  • 5Biotechnology, EnGeneIC, Sydney/AU

Abstract

Background

EnGeneIC has developed the EDVTM-Nanocell Platform Technology (EnGeneIC Dream Vector), which is a First-in-Class Cyto-Immuno-Therapy for the treatment of solid cancers. Cytotoxic drug, siRNA or miRNA are packaged into EDV nanocells, targeted to cancer cells via antibodies and payload is delivered intracellularly following internalisation of EDVs. EDVs are also taken up by immune system cells and stimulate the adaptive immune response resulting in a two-pronged anti-tumor approach. EGFR-targeted EDVs carrying mir15/16 mimics are currently being tested in a Phase 1 trial, with objective responses and prolonged disease control seen in refractory mesothelioma patients. The hypothesis for this Tailored EDV trial is that dosing patients with EGFR- targeted EDV's (EGFREDVs) with a payload tailored to an individual patient's tumour will result in enhanced anti-tumour effects, overcoming established drug resistance.

Trial design

An open-label Phase I feasibility study of a single delivery agent EGFREDVs containing clinician choice therapeutic payload(s) (cytotoxic drug, siRNA or miRNA) in subjects with advanced solid tumours who have failed standard treatments. The trial opened at the Northern Cancer Institute, Sydney, in August 2015 with 5 patients being recruited to date out of a possible 25 (ANZ CTR number : ACTRN12613001249741). Eligibility criteria include EGFR expression in tumour tissue using immunohistochemistry, measurable disease by standard radiological assessment according to RECIST, ECOG 0-1, and adequate organ function. The study design allows for one dose per week via a 20 minute infusion for 8 weeks. The first dose uses 2x109 nanocells and subsequent doses utilize 5x109 nanocells. Premedication comprises dexamethasone, promethazine and paracetamol and patients are monitored for a minimum period of 3 hours. Response assessments are undertaken at 8 weeks using standard imaging and relevant tumour markers. Exploratory cytokine analysis and analysis of immune cells is included.

Clinical trial identification

ANZ CTR number : ACTRN12613001249741

Legal entity responsible for the study

EnGeneIC Pty Ltd

Funding

EnGeneIC Pty Ltd

Disclosure

S. Sidhu: I am a shareholder of EnGeneIC Pty Ltd. H. Brahmbhatt: I am a Director of EnGeneIC P/L and hold shares in that entity. J. Macdiarmid: I am a Director of EnGeneIC P/L and hold shares in it. All other authors have declared no conflicts of interest.