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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new combination treatment is safe and effective for people with certain types of cancer, specifically pancreatic and ovarian cancer. The treatment includes two components: huCART-meso cells (a type of cell therapy) and VCN-01 (an experimental treatment). Participants will receive these treatments in different sequences to determine the best method. Suitable candidates have pancreatic cancer that cannot be surgically removed or ovarian cancer that has recurred or persists, and who have tried standard chemotherapy without success. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that huCART-meso cells are safe, though they may not work for everyone. This indicates the treatment is generally well-tolerated, but its effectiveness is limited.

For VCN-01, studies have found it is well-tolerated when combined with standard chemotherapy for pancreatic cancer patients. Safety data revealed that most patients handled the treatment well, though some experienced side effects that prevented dose increases.

Both treatments have been tested separately and are considered safe for humans based on previous studies. However, this trial remains in its early phase, focusing on understanding safety and how the body responds to the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for pancreatic cancer, which often involve chemotherapy and radiation, the combination of huCART-meso cells and VCN-01 offers a novel approach. huCART-meso is a type of cell therapy that uses genetically modified T-cells to specifically target and attack cancer cells. Meanwhile, VCN-01 is an oncolytic virus designed to selectively infect and destroy tumor cells, while also stimulating an immune response against the cancer. Researchers are excited because this dual-action strategy could potentially increase treatment effectiveness and target cancer cells more precisely, reducing the impact on healthy tissue.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

In this trial, participants will receive different combinations of huCART-meso cells and VCN-01. Research has shown that huCART-meso cells, specially modified immune cells, target a protein called mesothelin and have promising effects against tumors, particularly in pancreatic cancer. Early results suggest this treatment effectively eliminates cancer that has spread to the lungs. Meanwhile, VCN-01, a virus used in treatment, can break down the protective barrier around pancreatic cancer cells, enhancing the effectiveness of standard chemotherapy. Studies have found that patients who received VCN-01 with chemotherapy lived longer than those who only had the standard treatment. Together, these treatments may offer a new and more effective way to fight pancreatic cancer. ^{1 3 4 5 6}

Who Is on the Research Team?

Janos Tanyi, MD, PhD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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 for a Trial Participant

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).

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. therivabio.com therivabio.com/press_releases/theriva-biologics-announces-primary-endpoints-for-efficacy-and-safety-achieved-in-virage-phase-2b-clinical-trial-of-vcn-01-with-gemcitabine-nab-paclitaxel-in-newly-diagnosed-metastatic-pancre/

Theriva™ Biologics Announces Primary Endpoints for ... Patients treated with VCN-01 (zabilugene almadenorepvec) plus gemcitabine/nab-paclitaxel standard-of-care (SoC) chemotherapy had increased overall survival.

2. onclive.com onclive.com/view/vcn-01-plus-chemo-improves-survival-in-newly-diagnosed-metastatic-pancreatic-cancer

VCN-01 Plus Chemo Improves Survival in Newly ... Patients receiving VCN-01 had a median OS of 10.8 months versus 8.6 months with standard treatment, with a hazard ratio of 0.57.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8578996/

VCN-01 disrupts pancreatic cancer stroma and exerts ... VCN-01 antitumor activity was superior to gemcitabine alone, and the combination of both treatments was significantly better than either single ...

4. oncodaily.com oncodaily.com/oncolibrary/virage-trial-at-esmo25-pancreatic-cancer

VIRAGE Trial at ESMO 2025: Oncolytic Adenovirus VCN- ... The VIRAGE trial achieved its primary endpoints, demonstrating that the addition of VCN-01 to standard chemotherapy improves overall survival, ...

5. therivabio.com therivabio.com/press_releases/theriva-biologics-announces-positive-outcomes-from-the-second-meeting-of-the-independent-data-monitoring-committee-for-virage-the-companys-phase-2b-clinical-trial-of-vcn-01-in-combi/

The independent data monitoring committee ... The independent data monitoring committee (IDMC) considered VCN-01 to be well tolerated in metastatic PDAC patients treated with standard-of-care chemotherapy ...

6. oncnursingnews.com oncnursingnews.com/view/vcn-01-plus-soc-improves-survival-is-safe-in-metastatic-pdac

VCN-01 Plus SOC Improves Survival, Is Safe in Metastatic ... Patients receiving VCN-01 had a median DOR of 11.2 months (95% CI, 7.4-NE) vs 5.4 months (95% CI, 2.06-6.8) in the SOC arm (HR, 0.22; 95% CI, ...