CAR-T Cell Therapy for Relapsed Pancreatic Cancer

Overseen By Caroline Babinec

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: Concurrent malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 4 weeks

27 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this gene therapy research study is to test the safety and tolerability of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (iC9.CAR.B7-H3 T cells) in patients with pancreatic ductal adenocarcinoma that came back after receiving standard therapy for this cancer. The iC9.CAR.B7-H3 treatment is experimental and has not been approved by the Food and Drug Administration.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of this treatment for relapsed pancreatic cancer?

Research shows that CAR T cells targeting B7-H3 can control the growth of pancreatic cancer in lab and animal studies, suggesting potential effectiveness. Additionally, early studies indicate that CAR T cell therapy can safely trigger anti-tumor activity in pancreatic cancer patients. ^{1 2 3 4 5}

Is CAR-T cell therapy safe for humans?

Early findings suggest that CAR-T cell therapy is generally safe for humans, as it has been shown to be safe in early trials for pancreatic cancer, with the ability to trigger anti-tumor immune responses. ^{2 3 4 5 6}

How is the iC9-CAR.B7-H3 T cell treatment different from other treatments for pancreatic cancer?

The iC9-CAR.B7-H3 T cell treatment is unique because it uses genetically engineered T cells to specifically target the B7-H3 protein found on pancreatic cancer cells, potentially offering a more precise attack on the cancer with less harm to normal tissues. This approach is different from traditional treatments as it harnesses the body's immune system to fight the cancer, which is a novel strategy for this type of cancer. ^{1 2 3 4 7}

Research Team

Ashwin Somasundaram, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults over 18 with pancreatic ductal adenocarcinoma that has returned after standard treatment. Participants must be able to perform daily activities with minimal assistance (ECOG Performance Status of 0-1) and agree to use effective contraception methods. Those with other cancers or unwilling to follow study procedures are excluded.

Inclusion Criteria

My cancer is confirmed as pancreatic ductal adenocarcinoma.

I am 18 years old or older.

I will use two effective birth control methods if I can have children and am in this study.

Exclusion Criteria

I don't have another cancer that could affect this treatment's safety or results.

I am willing and able to follow the study's procedures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo lymphodepleting chemotherapy prior to CAR-T cell infusion

1 week

Treatment

Participants receive iC9.CAR.B7-H3 T cells infusion

Up to 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• iC9-CAR.B7-H3 T cells

Trial Overview The trial is testing the safety and effectiveness of a new gene therapy called iC9-CAR.B7-H3 T cell infusion, which involves modifying a patient's own immune cells to target cancer cells in relapsed pancreatic cancer.

Participant Groups

Group I: CAR-T Cell Therapy Experimental Treatment 1 Intervention

Single Arm Subjects with Refractory Pancreatic Ductal Adenocarcinoma (PDAC) cancer will receive iC9.CAR.B7-H3 T cells manufactured from their collected blood sample.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

Findings from Research

B7-H3.CAR-T cells effectively controlled the growth of various cancers, including pancreatic ductal adenocarcinoma, ovarian cancer, and neuroblastoma, in both laboratory and mouse models, indicating their potential as a powerful immunotherapy.

The use of 4-1BB co-stimulation in B7-H3.CAR-T cells led to lower PD-1 expression and enhanced antitumor activity, suggesting a mechanism that could improve the effectiveness of these CAR-T therapies without causing significant toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor Responses in the Absence of Toxicity in Solid Tumors by Targeting B7-H3 via Chimeric Antigen Receptor T Cells. Du, H., Hirabayashi, K., Ahn, S., et al.[2021]

A phase I trial of a multiantigen-specific T-cell therapy using patients' own nonengineered T cells showed safety and potential effectiveness in treating advanced pancreatic cancer.

Patients receiving this therapy, alongside chemotherapy, exhibited responses, suggesting that this approach could enhance treatment outcomes for those with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy Shows Promise in Pancreatic Cancer. [2020]

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]

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]

Autologous cytotoxic T lymphocytes (CTLs) specific for the CEA691 peptide can be successfully generated from pancreatic cancer patients, showing the potential for targeted immunotherapy against this cancer.

Blocking PD-L1 ex vivo significantly enhances the function of these CEA691-specific CTLs, particularly those isolated from tumor-draining lymph nodes, suggesting a promising strategy to improve anti-tumor responses in pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex Vivo PD-L1/PD-1 Pathway Blockade Reverses Dysfunction of Circulating CEA-Specific T Cells in Pancreatic Cancer Patients. Chen, Y., Xue, SA., Behboudi, S., et al.[2023]

Pancreatic tumors contain a variety of immune cells, including CD4+ T-cell subsets like regulatory T cells and TH17 cells, which actually support tumor growth instead of fighting it.

The study suggests that enhancing the body's antitumor immune response could be a promising strategy for preventing and treating pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune cells in pancreatic cancer: Joining the dark side. Zhang, Y., McAllister, F., Pasca di Magliano, M.[2022]

Pancreatic cancer is highly aggressive with a low 5-year survival rate of about 10%, and current treatments are limited, highlighting the urgent need for effective therapies.

While CAR T cell therapy has shown success in blood cancers, its effectiveness in pancreatic cancer is still limited; ongoing research is exploring strategies like enhancing CAR T cells and using alternative immune cells to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The next wave of cellular immunotherapies in pancreatic cancer. Yeo, D., Giardina, C., Saxena, P., et al.[2022]

References

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

Antitumor Responses in the Absence of Toxicity in Solid Tumors by Targeting B7-H3 via Chimeric Antigen Receptor T Cells. [2021]

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

Immunotherapy Shows Promise in Pancreatic Cancer. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

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

Ex Vivo PD-L1/PD-1 Pathway Blockade Reverses Dysfunction of Circulating CEA-Specific T Cells in Pancreatic Cancer Patients. [2023]

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

Immune cells in pancreatic cancer: Joining the dark side. [2022]

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

The next wave of cellular immunotherapies in pancreatic cancer. [2022]