A Clinical Trial to Evaluate EDV Nanocell Therapy With Gemcitabine and Nab-paclitaxel in Pancreatic Cancer
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.
Inclusion Criteria
- Histological or pathological confirmation of metastatic pancreas adenocarcinoma. Cytological or histological evidence of metastatic disease is required.
- Male or Female greater than or equal to 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance score of 0-1.
- Life expectancy ≥ 3 months in the opinion of the Investigator.
- Measurable disease as per iRECIST criteria.
- Subjects must have tumors that express EGFR.
- Documented disease progression with first line FOLFIRINOX or NALIRIFOX therapy, during or within 3 months (+/- 15 days) after end of therapy.
- No more than one line of prior systemic therapy for metastatic PDAC allowed.
- Albumin level > 3.0 g/dl
- Adequate hematological function.
- Adequate renal function.
- Adequate hepatic function.
- Adequate cardiac function with LVEF ≥ 50% at baseline.
- Reproductive criteria as follows:
- Female subjects who are of non-reproductive potential
- Female subjects of childbearing potential must have a negative serum pregnancy test within 14 days of the first dose.
- Female subjects must be willing to use highly effective methods of birth control during the period of therapy and for 6 months following the last study drug administration.
- Male subjects must be willing to use highly effective methods of birth control during the period of therapy and for 6 months following the last study drug administration.
- All study subjects must be willing to ensure that corresponding sexual partners practice these same methods of highly effective birth control for the same duration.
- The subject (or subject's legally authorized representative) has provided voluntary signed informed consent.
- According to the investigator's assessment, subject will be able to comply with the study protocol.
Exclusion Criteria
- Subjects currently receiving any other investigational agent.
- Unresolved (≥ Grade 1) non-hematological adverse events from prior anti-cancer therapy that is not controlled on maximal supportive therapy.
- Significant pericardial effusions, pleural effusions, or ascites that requires intervention. Subjects who require drainage within the last four weeks are ineligible.
- History of leptomeningeal or brain/CNS metastases.
- Ongoing treatment for other malignancies (hormone therapy acceptable).
- Patient may not have a history of malignancy other than PDAC within two years prior to screening except in circumstances where the risk of recurrence, metastasis or death in 5-years is <10%.
- Concurrent unstable diabetes mellitus or other contraindications for the use of corticosteroids that requires active titration of insulin.
- Subject has experienced a history of uncontrolled coronary artery disease, with or without angina pectoris or myocardial infarction, symptomatic congestive heart failure (New York Heart Association > Class II)
- Uncontrolled hypertension (systolic > 180 mmHg or diastolic > 100 mmHg) within two weeks.
- Uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy within the last four weeks.
- Baseline QTcF ≥ 450 ms (males) or ≥ 470 ms (females).
- Uncontrolled HIV infection. Patients without a prior diagnosis of HIV infection will undergo HIV testing unless not permitted to do so under local regulations. Patients with known HIV who have controlled infection (viral load undetectable and a CD4 count >350 either spontaneously or on a stable antiviral regimen) are permitted.
- Uncontrolled Hepatitis B virus (HBV) infection (chronic or acute).
- Uncontrolled Hepatitis C virus (HCV) infection.
- Uncontrolled arterial or venous thrombosis.
- Active or uncontrolled severe infection.
- Uncontrolled hypercalcemia (>2.6mmol/L or >10.3mg/dL) or symptomatic hypercalcemia requiring continued treatment for hypercalcemia.
- Received the following procedures within 21 days 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:
- 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.
- Any kind of disorder that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures.
- History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the Investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07049055.
Locations matching your search criteria
United States
New York
New York
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).
Trial PhasePhase I/II
Trial Typetreatment
Lead OrganizationEngeneic Pty Limited
Principal InvestigatorLinda Wu
- Primary IDENG15
- Secondary IDsNCI-2025-08615
- ClinicalTrials.gov IDNCT07049055