The purpose of this study is to evaluate the safety and tolerability and overall survival (OS) of E-EDV-D682/GC in combination with gemcitabine and nab-paclitaxel versus gemcitabine and nab-paclitaxel alone in participants with metastatic pancreatic ductal adenocarcinoma (PDAC) who have progressed on therapy.
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. Subsequent cycles will consist of weekly visits for 7 weeks. Following each 7-week treatment period is a treatment free week in which tumor 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 6 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).
E-EDV-D682 is a product based on the EnGeneIC EDV™ technology. EDVs are bacterially derived nanocells 400 nm in diameter that can be packaged with a range of different chemotherapeutic drugs and specifically targeted to cancer cell receptors via single chain bispecific antibodies (BsAb). E-EDV-D682 packages a chemotherapeutic payload PNU159682 into the EDV which targets the epidermal growth factor (EGFR) on cancer cells via a BsAb.
EDV-GC is a product based on the EnGeneIC EDV™ technology. EDVs are bacterially derived nanocells 400 nm in diameter that can be packaged with a range of different drugs. EDV-GC packages the immunomodulatory adjuvant aplha-galactosyl ceramide (GC) into the EDV and is designed to recruit anti-tumor immune cells.
Atlantic Health
Summit, New Jersey, United States
NOT_YET_RECRUITINGColumbia University Irving Medical Center
New York, New York, United States
NOT_YET_RECRUITINGTaylor Cancer Center
Maumee, Ohio, United States
RECRUITINGNumber of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0
All participants will be monitored for adverse events (AEs) and serious adverse events (SAEs) according to the CTCAE (Common Terminology Criteria for Adverse Events), Version 5 criteria. Incidence and severity of AEs will be reported for individual participants and treatment arms. The safety of Gemcitabine Nab-paclitaxel + E-EDV-D682/GC (Arm A) will be compared to Gemcitabine Nab-paclitaxel + placebo (Arm B).
Time frame: All adverse events will be monitored throughout the trial from the date of enrollment until 30 days after the last dose of study drug, on average 9 months.
Duration of time from the start of treatment that participants are still alive.
A primary objective of the randomized, blinded Phase IIa stage of the study is to examine the overall survival rate for each treatment arm. i.e. Gemcitabine Nab-paclitaxel + E-EDV-D682/GC (Arm A), compared to Gemcitabine Nab-paclitaxel + placebo (Arm B). Overall survival is defined as time from the date of first administration of drug to the date of death, regardless of cause. Kaplan Meier curves will be utilized to determine percentage and median survival. The primary hypotheses that the IMP treatment improves overall survival versus standard-of-care chemotherapy will be assessed using statistical models defined in the study protocol.
Time frame: Overall survival will be monitored from the date of first dose to the end of the treatment period (on average 9 months), then at 3 month intervals following discontinuation of study treatment for a minimum period of 12 months.
The number of days from the date of first administration of EDVs to the date of radiological evidence of disease progression
Progression free survival (PFS) will be calculated from all participants as the number of days from the date of first administration of EDVs to the date of radiological evidence of disease progression (date of MRI scan) or death, regardless of cause. A comparison of the PFS will be made between the two treatment Arms.
Time frame: Imaging will be performed at baseline (screening) and at the completion of every cycle of treatment (8 weeks) until disease progression is confirmed by iRECIST or death, whichever comes first, up to 24 months.
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
144
Gemcitabine in combination with nab-paclitaxel is routinely used as second-line therapy in metastatic PDAC patients who have either progressed on or are intolerant to 5-FU based combination in the first line setting. In this trial the safety and efficacy of E-EDV-D682/GC will be tested in combination with a reference therapy - gemcitabine and nab-paclitaxel.
Nab-paclitaxel in combination with gemcitabine is routinely used as second-line therapy in metastatic PDAC patients who have either progressed on or are intolerant to 5-FU based combination in the first line setting. In this trial the safety and efficacy of E-EDV-D682/GC will be tested in combination with a reference therapy - gemcitabine and nab-paclitaxel.
Percentage of participants with immune complete response (iCR) or immune partial response (iPR)
The Objective Response Rate (ORR) will be measured as the percentage of participants with immune complete response (iCR) or immune partial response (iPR). A comparison of the ORR will be made between the two treatment Arms.
Time frame: Imaging will be performed at baseline (screening) and at the completion of every cycle of treatment (8 weeks) until the participant is withdrawn from treatment (up to 24 months).
Time from initial response to disease progression
The Duration of Response (DOR) will be measured as the time from the initial complete or partial response until disease progression or death, whichever comes first. A comparison of the DOR will be made between the two treatment Arms.
Time frame: Imaging will be performed at baseline (screening) and at the completion of every cycle of treatment (8 weeks) until the participant has confirmed disease progression per iRECIST or death, whichever comes first, up to 24 months.
The proportion of participants with a disease response at 4 months after treatment initiation
The Disease Control Rate (DCR) will be measured as the proportion of participants with immune complete response (iCR), immune partial response (iPR) and immune stable disease (iSD) at 4 months after treatment initiation. A comparison of the DCR will be made between the two treatment Arms.
Time frame: Imaging will be performed at baseline (screening) and at the completion of cycle 2 of treatment (16 weeks).