A Clinical Trial to Evaluate EDV Nanocell Therapy With Gemcitabine and Nab-paclitaxel in Pancreatic Cancer

This study is testing an experimental treatment for participants with metastatic PDAC who have progressed following first line therapy involving 5-fluorouracil-containing combination that included irinotecan and oxaliplatin.

The experimental treatment consists of a chemotherapy drug, PNU-159682 packaged inside an EDV™ nanocell targeted to the epidermal growth factor receptor (EGFR) to form the investigational product E-EDV-D682. The EnGeneIC Dream Vector (EDV) nanocell 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 cells 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 alpha-galactosylceramide (GC) called EDV-GC. The combination of these 2 drugs is known as E-EDV-D682/GC.

The trial is a randomized blinded Phase I/IIa study that aims to test the safety and efficacy of E-EDV-D682/GC in combination with gemcitabine and nab-paclitaxel. The trial consists of 2 cohorts:

* Cohort 1 is an initial safety run-in phase that includes at least six participants who will receive E-EDV-D682/GC in combination with gemcitabine and nab-paclitaxel to assess safety. If one or less of the participants experience a dose limiting toxicity (DLT), the randomization portion of the study will be activated. If two or more DLTs occur, then the dose level will be reduced for the following participants. Cohort 1 enrollment will be complete once the first six evaluable participants have completed the DLT evaluation period, the study will then proceed to the randomized, blinded expansion phase. * Cohort 2 is the randomized phase II expansion phase of the trial:

Participants will be randomized 2:1 to ARM A or ARM B, respectively:

1. ARM A. E-EDV-D682/GC with gemcitabine and nab-paclitaxel (N = 92) 2. ARM B. Gemcitabine and nab-paclitaxel with placebo (N = 46)

The first treatment cycle for all participants will involve bi-weekly visits for 3 weeks with a treatment free week in week 4, followed by weekly visits for a further 3 weeks. Doses of E-EDV-D682/GC in 3mL of 0.9% sodium chloride are administered intravenously over 10 seconds. In week 8, tumor burden will be radiologically re-evaluated in accordance with immune Response Evaluation Criteria in Solid Tumors (iRECIST) guidelines to determine treatment response.