huCART-meso + VCN-01 for Pancreatic Cancer

Overseen By Abramson Cancer Center Clinical Trials Services

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: PD-1 inhibitors

Disqualifiers: CNS metastases, Active cancer, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 14 days per cohort

13 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on high-dose corticosteroids or certain immunotherapy drugs, you may need to stop or adjust them before participating.

What data supports the effectiveness of the huCART-meso + VCN-01 treatment for pancreatic cancer?

Research shows that T cells engineered with chimeric antigen receptors (CAR T cells) can target and kill cancer cells in pancreatic cancer models, particularly those expressing mesothelin, a protein often found in these tumors. These CAR T cells have been effective in reducing tumor growth and eliminating metastases in animal studies, suggesting potential for treating pancreatic cancer in humans. ^{1 2 3 4 5}

Is the huCART-meso + VCN-01 treatment safe for humans?

The research on CAR T cell therapy, which includes huCART-meso, suggests it can be effective against pancreatic cancer cells, but there are concerns about safety, particularly 'on-target, off-tumor' toxicity, which means the treatment might affect healthy cells as well. The studies focus on improving safety by using different methods to engineer the cells, but specific safety data for humans is not detailed in the available research. ^{1 2 5 6 7}

What makes the huCART-meso + VCN-01 treatment unique for pancreatic cancer?

The huCART-meso + VCN-01 treatment is unique because it combines genetically modified immune cells (huCART-meso) with an oncolytic virus (VCN-01) to target pancreatic cancer, offering a novel approach compared to traditional chemotherapy. This combination aims to enhance the immune system's ability to recognize and destroy cancer cells while the virus selectively infects and kills tumor cells. ^{3 8 9 10 11}

What is the purpose of this trial?

This trial is testing a combination of modified immune cells and a virus-based therapy in patients who may not have responded to other treatments. The immune cells are designed to target and destroy cancer cells, while the virus helps by killing cancer cells and enhancing the immune response. The virus therapy has been approved for the treatment of metastatic melanoma.

Research Team

Janos Tanyi, MD, PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults with specific advanced cancers: unresectable or metastatic pancreatic adenocarcinoma, and persistent or recurrent serous epithelial ovarian cancer. Participants must have tried at least one standard chemotherapy, be in good physical condition (ECOG 0-1), not need oxygen therapy, and have no other active invasive cancers or significant health issues like heart disease, autoimmune diseases requiring steroids, or certain infections.

Inclusion Criteria

Subjects providing written informed consent

My organs and bone marrow are functioning well.

My pancreatic cancer cannot be removed by surgery and has spread.

Exclusion Criteria

Pregnant or breastfeeding women

I do not have serious heart fluid buildup or heart conditions that could affect the study.

I have chronic hepatitis C with moderate to severe liver scarring.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VCN-01 and huCART-meso cells in a 3+3 dose escalation design. Cohort 1 receives VCN-01 on Day 0 and huCART-meso on Day 14. Cohort 2 receives a higher dose of VCN-01 on Day 0 and huCART-meso on Day 14. Cohort -1, if needed, receives huCART-meso on Day 0 and VCN-01 on Day 10.

14 days per cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment, with formal DLT assessments performed by the Clinical PI and Sponsor Medical Director.

6 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if the dose combination is identified as the recommended phase 2 dose (RP2D).

Treatment Details

Interventions

• huCART-meso Cells
• VCN-01

Trial Overview The study tests a combination of huCART-meso cells and VCN-01 on patients with ovarian and pancreatic cancer using a '3+3 dose escalation' method to find the safest dose. This means small groups of patients receive increasing doses until doctors determine the highest dose that can be given safely.

Participant Groups

Group I: Cohort 2 Active Control 2 Interventions

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.

Group II: Cohort -1 Active Control 2 Interventions

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.

Group III: Cohort 1 Active Control 2 Interventions

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.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Theriva Biologics

Collaborator

Trials

1

Recruited

10+

Theriva Biologics SL

Industry Sponsor

Trials

5

Recruited

180+

VCN Biosciences, S.L.

Industry Sponsor

Trials

5

Recruited

180+

Findings from Research

Meso-CART cells, engineered T cells targeting mesothelin, showed promising anti-tumor effects against pancreatic cancer, particularly in eliminating lung metastases in mice, indicating potential for treating advanced stages of the disease.

This study is the first to demonstrate that meso-CART cells can effectively target and reduce distant metastases, suggesting they could be a viable immunotherapy option for patients with mesothelin-positive pancreatic tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered T lymphocytes eliminate lung metastases in models of pancreatic cancer. Sun, Q., Zhou, S., Zhao, J., et al.[2019]

The study developed dual-receptor CAR-modified T cells (dCAR-T) that effectively target pancreatic cancer cells expressing both carcino-embryonic antigen (CEA) and mesothelin (MSLN), demonstrating high anti-tumor activity in vitro and in vivo.

dCAR-T cells showed significant cytotoxicity against tumor cells with both antigens while sparing those with only one, reducing the risk of 'on-target, off-tumor' toxicity and allowing for more precise CAR-T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombination of a dual-CAR-modified T lymphocyte to accurately eliminate pancreatic malignancy. Zhang, E., Yang, P., Gu, J., et al.[2021]

A new method successfully cultured primary pancreatic cancer cell lines (PPCLs) from patient-derived xenografts, achieving a 100% success rate in expanding these cells, which helps preserve the tumor's original characteristics.

The PPCLs maintained intratumoral heterogeneity and expressed key cancer and immune markers, making them a valuable tool for personalized therapy research and better understanding of pancreatic cancer biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of Pancreatic Cancer Cells from a Patient-Derived Xenograft Model Allows for Practical Expansion and Preserved Heterogeneity in Culture. Pham, K., Delitto, D., Knowlton, AE., et al.[2018]

Adoptive cell therapy using CAR-engineered T cells shows promise as a safe treatment option for patients with pancreatic ductal adenocarcinoma, indicating it may help restore effective immune surveillance against tumors.

Early results suggest that CAR T cells not only have the ability to attack tumors directly but also stimulate the body's own immune system to fight cancer, enhancing overall anti-tumor responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered chimeric antigen receptor-expressing T cells for the treatment of pancreatic ductal adenocarcinoma. Beatty, GL.[2023]

Pancreatic cancer is projected to become the second leading cause of cancer-related deaths in the U.S. by 2030, highlighting the urgent need for new treatment options, as current immunotherapies have shown limited effectiveness.

Chimeric antigen receptor (CAR) T cell therapy is emerging as a promising treatment for pancreatic cancer, utilizing genetically engineered T cells to target specific cancer-associated antigens, with ongoing preclinical and early clinical trials exploring its efficacy and potential combinations with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Potential of CAR T Cell Therapy in Pancreatic Cancer. Akce, M., Zaidi, MY., Waller, EK., et al.[2022]

Two novel patient-derived cell lines from pancreatic ductal adenocarcinoma (PDAC) tumors, LuPanc-1 and LuPanc-2, exhibit distinct molecular characteristics and responses to treatment, highlighting the importance of individual tumor biology in therapy selection.

LuPanc-1 cells showed greater sensitivity to gemcitabine and FOLFIRINOX compared to LuPanc-2, suggesting that these cell lines can be used to explore personalized treatment strategies for PDAC based on their unique genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment and Molecular Characterization of Two Patient-Derived Pancreatic Ductal Adenocarcinoma Cell Lines as Preclinical Models for Treatment Response. Braun, R., Lapshyna, O., Watzelt, J., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Engineered T lymphocytes eliminate lung metastases in models of pancreatic cancer. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Recombination of a dual-CAR-modified T lymphocyte to accurately eliminate pancreatic malignancy. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Isolation of Pancreatic Cancer Cells from a Patient-Derived Xenograft Model Allows for Practical Expansion and Preserved Heterogeneity in Culture. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Engineered chimeric antigen receptor-expressing T cells for the treatment of pancreatic ductal adenocarcinoma. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Potential of CAR T Cell Therapy in Pancreatic Cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Generation of Induced Pluripotent Stem Cell-Like Lines from Human Pancreatic Ductal Adenocarcinoma. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Engraftment of mesothelin chimeric antigen receptor using a hybrid Sleeping Beauty/minicircle vector into NK-92MI cells for treatment of pancreatic cancer. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Establishment and Molecular Characterization of Two Patient-Derived Pancreatic Ductal Adenocarcinoma Cell Lines as Preclinical Models for Treatment Response. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Complex Tumor Spheroids, a Tissue-Mimicking Tumor Model, for Drug Discovery and Precision Medicine. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Characterization of a cancer stem cell-like side population derived from human pancreatic adenocarcinoma cells. [2022]

11. Greece pubmed.ncbi.nlm.nih.gov

Establishment of a novel human cell line retaining the characteristics of the original pancreatic adenocarcinoma, and evaluation of MEK as a therapeutic target. [2021]