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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy for individuals whose pancreatic cancer has returned after standard treatments. The treatment uses modified immune cells, called CAR-T cells, to target and attack cancer cells. Specifically, it involves iC9-CAR.B7-H3 T cells, also known as Autologous CAR-T Cells Targeting B7-H3. Researchers primarily aim to understand the safety and tolerability of this treatment for patients. This trial suits those with a confirmed diagnosis of pancreatic cancer that has recurred after previous treatments. Participants will have cells collected from their blood to create a treatment tailored specifically for them. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that a new treatment, iC9-CAR.B7-H3 T cells, is being tested for safety in treating pancreatic cancer that has returned after standard treatments. This treatment remains experimental and lacks FDA approval.

Studies suggest that using these CAR-T cells after chemotherapy with cyclophosphamide and fludarabine might be safe and manageable. However, as this is an early phase study, the primary goal is to assess safety, and complete safety information is not yet available. Early studies like this one are crucial for understanding treatment tolerance and monitoring side effects.

Participants should know that since the treatment is in the early stages, safety information, though encouraging, is still being collected. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about iC9-CAR.B7-H3 T cells for relapsed pancreatic cancer because this treatment uses a unique approach called CAR-T cell therapy. Unlike traditional treatments like chemotherapy and radiation, which target cancer cells broadly, CAR-T cell therapy engineers a patient's own immune cells to specifically target and attack cancer cells. This particular treatment focuses on a protein called B7-H3 that is found on pancreatic cancer cells, potentially increasing the precision and effectiveness of the attack. By harnessing the body's immune system in this targeted way, there’s hope for better outcomes and fewer side effects compared to conventional therapies.

What evidence suggests that this treatment might be an effective treatment for pancreatic cancer?

Research shows that a new treatment using iC9-CAR.B7-H3 T cells could help treat pancreatic cancer that returns after standard treatments. Participants in this trial will receive these special T cells, which are designed to find and attack a protein called B7-H3 on cancer cells. By targeting this protein, the T cells may reduce the number of cancer cells. Early results suggest that this treatment might prevent the cancer from returning by eliminating small cancer cells left after the initial treatment. Although still under testing, this treatment offers hope for people with recurring pancreatic cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Ashwin Somasundaram, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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

I am a male and will use effective birth control during and for 3 months after the 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/84/2_Supplement/A021/732733/Abstract-A021-Adjuvant-iC9-B7-H3-CAR-T-cell-based

Abstract A021: Adjuvant iC9.B7-H3 CAR T cell-based ... iC9.B7-H3 CAR T cells may be an effective adjuvant treatment for the eradication of micro-metastases and the prevention of disease recurrence in PDAC patients.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06158139?term=AREA%5BBasicSearch%5D(T%20cell%20chimeric)&rank=4

NCT06158139 | Autologous CAR-T Cells Targeting B7-H3 ... Single Arm Subjects with Refractory Pancreatic Ductal Adenocarcinoma (PDAC) cancer will receive iC9.CAR.B7-H3 T cells manufactured from their collected blood ...

3. unclineberger.org unclineberger.org/wp-content/uploads/sites/867/2024/08/PCCE-Clinical-Trials-Locally-Advanced.pdf

Autologous CAR-T Cells Targeting B7-H3 in Pancreatic ... Description: This is a research study to evaluate how the genetic makeup of Pancreatic Ductal Adenocarcinoma. (PDAC) can affect the response to FDA-approved ...

4. cancer.gov cancer.gov/clinicaltrials/NCI-2024-03897

Chimeric Antigen Receptor (CAR) T-cell Therapy with iC9- ... Giving iC9-CAR.B7-H3 T-cells following lymphodepleting chemotherapy with cyclophosphamide and fludarabine may be safe, tolerable, and/or effective for the ...

5. researchforme.unc.edu researchforme.unc.edu/study-details?rcid=5366

Phase I Study of CAR-T Cells Targeting the B7-H3 Antigen ... This is a research study for patients with pancreatic ductal adenocarcinoma that came back after receiving standard therapy.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06347068

Study of Autologous CAR-T Cells Targeting B7-H3 in ... This phase 1, single-center, open-label study explores the safety of escalating doses of chimeric antigen receptor T cells (CAR-T) cells in subjects with ...