huCART-meso + VCN-01 in Pancreatic and Ovarian Cancer

Phase 1 Trial of Human Chimeric Antigen Receptor Modified T Cells (huCART-meso) Administered in Combination With VCN-01 in Patients With Pancreatic and Serous Epithelial Ovarian Cancer

This is a single-center phase 1 study to evaluate the safety and feasibility of huCART-meso cells given in combination with VCN-01 in patients with unresectable or metastatic pancreatic adenocarcinoma and serous epithelial ovarian cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer; Serous Ovarian Cancer
• Intervention / Treatment: Biological: VCN-01; Biological: huCART-meso Cells

Detailed Description

This is a Phase I study evaluating the safety and feasibility of lentiviral transduced huCARTmeso cells when given in combination with VCN-01.

Dose Finding Phase:

This study was initiated using a 3+3 dose (de)escalation design in order to explore the initial safety of these drugs when given in combination, as well as to establish the recommended expansion dose of VCN-01 in this setting.

Expansion Phase:

The trial was expanded to include two parallel treatment arms further exploring the dosing sequence and schedule of these two investigational products when given in combination.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with one of the following diagnoses:

   1. Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma; OR
   2. Persistent or recurrent serous epithelial ovarian cancer
2. Progression or intolerance to at least one prior standard of care chemotherapy for advanced stage disease.
3. Subjects must have measurable disease as defined by RECIST 1.1 criteria.
4. Patients ≥ 18 years of age.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Adequate organ and bone marrow function defined as:

   1. Hemoglobin ≥ 9 g/dL
   2. Platelets ≥ 75,000/µl
   3. PT/INR and PTT ≤ 1.5 x ULN
   4. Bilirubin ≤ 2.0 x ULN
   5. Creatinine ≤ 1.5 x ULN
   6. ALT/AST ≤ 5 x ULN (subjects with liver metastases) or ALT/AST ≤ 2.5 x ULN (subjects without liver metastases)
   7. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air
   8. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
7. Provides written informed consent.
8. Subjects of reproductive potential must agree to use acceptable birth control methods, as described in the protocol

Exclusion Criteria:

1. Patients with known CNS metastases
2. Active invasive cancer other than the one of the two cancers targeted by this study. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder and prostate cancer with PSA level < 1.0) are not excluded.
3. Active hepatitis B or hepatitis C infection.
4. Chronic hepatitis C with a FibroScan score equivalent to fibrosis stage 2 (F2) or greater.
5. Patients with known cirrhosis.
6. Patients with ongoing or active infection.
7. Patients with a known history of Li Fraumeni syndrome or retinoblastoma protein pathway germinal deficiency.
8. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10 mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
9. Planned concurrent treatment with systemic high dose corticosteroids. Patients may be on a stable low dose of steroids (≤ 10mg equivalent of prednisone). Use of inhaled steroids is allowable.
10. Patients requiring supplemental oxygen therapy.
11. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
12. Any clinically significant pericardial effusion, Class II-IV cardiovascular disability according to the New York Heart Association Classification or other cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study. This determination will be made by a cardiologist if cardiac issues are suspected.
13. Pregnant or breastfeeding women.
14. RETIRED WITH PROTOCOL VERSION 5.

15. Patients with significant lung disease as follows:

    1. Patients with radiographic evidence of greater than lobar lymphangitic pulmonary involvement, greater than lobar bronchial wall thickening suggestive of peribronchial lymphatic disease extension, and/or evidence of extensive bilateral parenchymal metastatic burden.
    2. Patients with radiographic and/or clinical evidence of active radiation pneumonitis.
    3. Patients with radiographic evidence of underlying interstitial lung disease, including evidence of unresolved drug toxicity from any agent (e.g. chemotherapy, targeted agents, amiodarone, nitrofurantoin, etc.)
16. Patients with prior/ongoing treatment that will not accommodate washout requirements for immune checkpoint inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Single dose of 3.3x10(12) vp of VCN-01 on Day 0, followed by a single dose of 5x10(7) of huCART-meso cells on Day 14.	Biological: VCN-01; Intravenous administration of VCN-01; Biological: huCART-meso Cells; Intravenous administration of huCART-meso cells
Experimental: Cohort 2; Single dose of 1x10(13) vp of VCN-01 on Day 0, followed by a single dose of 5x10(7) of huCART-meso cells on Day 14.	Biological: VCN-01; Intravenous administration of VCN-01; Biological: huCART-meso Cells; Intravenous administration of huCART-meso cells
Experimental: Cohort -1; In the event that 2 DLTs occur in Cohort 1, then enrollment in Cohort 1 will be stopped and Cohort -1 will be opened for evaluation. Enrolled subjects will receive a single dose of huCART-meso cells on Day 0 followed by a single dose of 3.3x10(12) vp of VCN-01 on Day 14.	Biological: VCN-01; Intravenous administration of VCN-01; Biological: huCART-meso Cells; Intravenous administration of huCART-meso cells
Experimental: Expansion Arm A; Recommended expansion dose of VCN-01 as a single IV infusion on Day 0, followed by a single dose of 5x10^7 huCART-meso cells on Day 7 (+3d) via IV infusion.	Biological: VCN-01; Intravenous administration of VCN-01; Biological: huCART-meso Cells; Intravenous administration of huCART-meso cells
Experimental: Expansion Arm B; Single dose of 5x10^7 huCART-meso cells on Day 0 via IV infusion followed by the recommended expansion dose of VCN-01 as a single IV infusion on Day 7 (+3d).	Biological: VCN-01; Intravenous administration of VCN-01; Biological: huCART-meso Cells; Intravenous administration of huCART-meso cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type, frequency, severity, and attribution of AEs/SAEs as assessed by CTCAE v 5.0		2 years
Occurrence of dose-limiting toxicities.		2 years
Recommended expansion dose of VCN-01 administered in combination with huCART-meso cells	highest VCN-01 dose at which 0 or 1 DLT occurs in 6 DLT-evaluable subjects	42 days after Infusion #1 (huCART-meso cells or VCN-01 dependent on cohort assignment)
Occurrence of treatment-limiting toxicities (TLTs)	Number of subjects who either a) receive huCARTmeso cells and VCN-01 as per their arm assignment, or b) have a TLT qualifying event after receipt of either VCN-01 or huCART-meso cells.	28 days after Infusion #1 (huCART-meso cells or VCN-01 dependent on arm assignment)
Comparison of the safety profiles of the two treatment arms via descriptive analysis		Up to 15 years post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		15 years
Overall Response Rate (ORR)		15 years
Best Overall Response (BOR)		15 years
Duration of Response (DOR)		15 years
Progression Free Survival (PFS)		15 years
Proportion of subjects enrolled who receive one or both of the intended study infusions	In the Expansion Phase, the proportion of subjects in each treatment arm will be compared via descriptive analysis.	2 years

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Theriva Biologics SL
• Investigators: Principal Investigator: Janos L. Tanyi, MD, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2022
• Primary Completion (Estimated): September 1, 2038
• Study Completion (Estimated): September 1, 2038

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: September 15, 2021
• First Posted (Actual): September 27, 2021

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: UPCC# 03821, IND #27590

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No