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

NCT07049055 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ENG15
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Pancreatic Cancer, Metastatic; PDAC - Pancreatic Ductal Adenocarcinoma

Keywords

PDAC; Molecular Targeted Therapy; Drug Delivery Systems; Pancreatic Cancer; Epidermal Growth Factor Receptor; Bispecific Antibodies; Antineoplastic Agents; Immunotherapy; Disease Progression

Outcome Measures

Primary Outcomes (2)

• Number 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).

  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.

  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.

Secondary Outcomes (4)

• The number of days from the date of first administration of EDVs to the date of radiological evidence of disease progression

  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.

• Percentage of participants with immune complete response (iCR) or immune partial response (iPR)

  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

  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

  Imaging will be performed at baseline (screening) and at the completion of cycle 2 of treatment (16 weeks).

Study Arms (2)

Cohort 2 Arm A

EXPERIMENTAL

E-EDV-D682/GC with gemcitabine and nab-paclitaxel

Drug: E-EDV-D682; Drug: EDV-GC; Drug: Gemcitabine; Drug: Nab paclitaxel.

Cohort 2 Arm B

PLACEBO COMPARATOR

gemcitabine and nab-paclitaxel with placebo

Drug: Gemcitabine; Drug: Nab paclitaxel.

Interventions

E-EDV-D682 DRUG

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.

Cohort 2 Arm A

EDV-GC DRUG

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.

Cohort 2 Arm A

Gemcitabine DRUG

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.

Cohort 2 Arm A; Cohort 2 Arm B

Nab paclitaxel. DRUG

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.

Cohort 2 Arm A; Cohort 2 Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Engeneic Pty Limited: lead
• Herbert Irving Comprehensive Cancer Center: collaborator

Study Sites (4)

Chan Soon-Shiong Institute for Medicine

El Segundo, California, 90245, United States

ACTIVE NOT RECRUITING

Atlantic Health

Summit, New Jersey, 07901, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Taylor Cancer Center

Maumee, Ohio, 43537, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasm Metastasis; Disease Progression

Interventions

Gemcitabine; Taxes

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Economics; Health Care Economics and Organizations

Study Officials

• Dr Linda Y.Wu, MD

  Columbia University Medical Center/ Herbert Irving Pavilion

  PRINCIPAL INVESTIGATOR

• Dr Jennifer MacDiarmid, Ph.D

  Engeneic Pty Limited

  STUDY DIRECTOR

• Dr Himanshu Brahmbhatt, Ph.D

  Engeneic Pty Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized blinded Phase I/IIa study to test the safety and efficacy of E-EDV-D682/GC in combination with gemcitabine and nab-paclitaxel. The study design is based on an initial safety run-in using a rolling 6 model prior to randomization into two treatment arms. The initial safety run-in (Cohort I) will assess safety and tolerability of E-EDV-D682/GC in combination with gemcitabine and nab-paclitaxel in subjects with metastatic PDAC. In Cohort 2 subjects will be randomized into two treatment arms consisting of E-EDV-D682/GC with gemcitabine and nab-paclitaxel or gemcitabine and nab-paclitaxel with placebo.

Study Record Dates

• First Submitted: May 29, 2025
• First Posted: July 3, 2025
• Study Start: January 12, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)