CAR-T Cells for Ovarian Cancer

Overseen By Caroline Babinec

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: Concurrent malignancy, Non-compliance, others

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

Compensation: Varies

Number of Visits: 4

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to find a safe dose of a new treatment, iC9-CAR.B7-H3 T cells, for ovarian cancer that has returned after standard treatments. This involves using a patient's own modified immune cells to target cancer cells. The trial targets those with a specific type of ovarian cancer that did not respond to or relapsed soon after platinum-based chemotherapy and have undergone at least two previous treatment regimens. Participants will have their T cells collected and modified, then receive them back through an infusion. The main focus is to ensure the treatment's safety and to determine the highest dose that can be tolerated without severe side effects. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

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

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

Studies have shown that iC9-CAR.B7-H3 T cells target a specific protein on ovarian cancer cells. In animal studies, these cells demonstrated a strong ability to attack cancer cells while sparing normal tissues. This suggests a level of safety, but it’s important to remember that this is an early trial.

As a Phase 1 trial, the main focus is on testing safety and determining the right dose. Researchers use these early trials to learn about any side effects in humans. So far, the treatment remains experimental and lacks FDA approval. Participants in this trial will help determine how well the treatment is tolerated and what dose can be safely administered without causing excessive side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for ovarian cancer, which often include surgery and chemotherapy, iC9-CAR.B7-H3 T cells represent a cutting-edge approach by harnessing the power of the immune system. This experimental treatment involves modifying a patient's own T cells to specifically target and destroy cancer cells, thanks to a unique mechanism called chimeric antigen receptor (CAR) technology. Researchers are excited about this treatment because it offers the potential for a more precise attack on cancer cells, possibly leading to fewer side effects and better outcomes compared to conventional therapies.

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

Research has shown that iC9-CAR.B7-H3 T cells, the treatment under study in this trial, could be promising in fighting ovarian cancer. These specially modified T cells are designed to attack and destroy cancer cells by targeting a specific protein called B7-H3, often found in high amounts in ovarian cancer. In lab tests, these T cells reduced cancer cell numbers more effectively than regular T cells. The treatment also aims to prevent the T cells from losing effectiveness over time, potentially enhancing long-term results. Although still under investigation, early results suggest this approach could be a strong option for treating ovarian cancer that has recurred after standard treatments. ^{1 2 4 5 6}

Who Is on the Research Team?

Linda Van Le

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with ovarian cancer that has returned after standard treatment. Participants must have sufficient T cells to modify, and meet specific health criteria not detailed here.

Inclusion Criteria

I am able to get out of my bed or chair and move around.

My cancer came back or got worse within 6 months after platinum chemotherapy.

Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information explained to, understood by and signed by the subject or legally authorized representative

Exclusion Criteria

I do not have another cancer that could affect the trial's safety or results.

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

I am not willing to have biopsies before, during, and after treatment if my doctor thinks it's safe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion Chemotherapy

Subjects receive lymphodepletion chemotherapy prior to CAR-T cell infusion

1 week

1 visit (in-person)

CAR-T Cell Treatment

iC9-CAR.B7-H3 T cells are infused into subjects after lymphodepletion chemotherapy

3 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after CAR-T cell treatment

4 weeks

2 visits (in-person)

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• iC9-CAR.B7-H3 T cells

Trial Overview The study tests a new therapy using modified T cells (iC9-CAR.B7-H3) after chemotherapy with Fludarabine and Cyclophosphamide. It's in two parts: cell collection/modification, then infusion post-chemotherapy.

How Is the Trial Designed?

Group I: Chimeric Antigen Receptors Experimental Treatment 3 Interventions

blood will be collected to prepare the iC9-CAR.B7-H3 T cells. Disease-fighting T cells will be isolated and modified to prepare the iC9-CAR.B7-H3 T cells. In part 2, the iC9-CAR.B7-H3 T cells are given by infusion after completion of lymphodepletion chemotherapy.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Published Research Related to This Trial

Chimeric antigen receptor-modified T (CAR-T) cell therapy shows promising clinical efficacy in treating ovarian cancer, as supported by various preclinical experiments and clinical trials.

While CAR-T therapy offers a novel approach to cancer treatment, it is associated with side effects and toxicities, including cytokine release syndrome and 'on-target, off-tumor' effects, which need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cell therapy in ovarian cancer: from the bench to the bedside. Zhu, X., Cai, H., Zhao, L., et al.[2019]

Adoptive T-cell therapies, particularly CAR T-cell therapy, are gaining attention for their potential to enhance immune responses against ovarian cancer, leveraging T cells' critical role in immune surveillance.

Recent advancements, such as dual specificity CARs and affinity-tuned single-chain Fv fragments, may improve the effectiveness and safety of CAR T-cell therapies compared to traditional T cell receptor therapies in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of chimeric antigen receptor-engineered T cells in ovarian cancer therapy. Zhang, M., Zhang, DB., Shi, H.[2021]

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 specific population of tissue-resident memory T cells (TIM-3/CXCL13-positive) was identified in epithelial ovarian cancer (EOC), which is associated with improved survival in patients, based on analysis of around 175 patients with high-grade serous EOC.

The study suggests that combining TIM-3 and PD-1 blockade therapies could enhance anti-cancer immunity in EOC, particularly since CXCL13-positive CD8 T cells are linked to better responses to existing immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor infiltrating CD8/CD103/TIM-3-expressing lymphocytes in epithelial ovarian cancer co-express CXCL13 and associate with improved survival. Vlaming, M., Bilemjian, V., Freile, JÁ., et al.[2022]

B7-H3 is a promising target for immunotherapy in solid tumors due to its overexpression in tumors and limited presence in normal tissues, making it a suitable candidate for chimeric antigen receptor (CAR) therapies.

Initial trials of B7-H3-targeted CAR-T cell therapies have shown safety, but their effectiveness has been limited; strategies such as local delivery, enhancing CAR-T cell persistence, and combining with other treatments may improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3-targeted CAR-T cell therapy for solid tumors. Li, G., Wang, H., Wu, H., et al.[2022]

In ovarian cancer, PD-L1 is not highly expressed, and instead, B7-H3 is a major checkpoint molecule that contributes to T-cell exhaustion and immunosuppression in the tumor microenvironment.

Blocking B7-H3, rather than PD-1, significantly improved survival in mouse models of ovarian cancer, suggesting that targeting B7-H3 could be a promising strategy for patients who do not respond to existing PD-L1/PD-1 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-expressed B7-H3 mediates the inhibition of antitumor T-cell functions in ovarian cancer insensitive to PD-1 blockade therapy. Cai, D., Li, J., Liu, D., et al.[2022]

The study analyzed T-cell receptor (TCR) changes in ovarian carcinoma using samples from 24 malignant and 23 benign masses, revealing that TCRB-B positivity was higher in malignant cases, suggesting a potential role in immune response to cancer.

Higher levels of TCRG-B were associated with earlier-stage tumors and better overall survival, indicating that understanding TCR pathways could lead to new immunotherapy approaches for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The investigation of T-cell receptor subtypes in ovarian cancer: effects on survival and prognostic factors. Özkan, S., Selvi Gunel, N., Aygünes, D., et al.[2021]

B7-H4 CAR T cell therapy effectively targets and kills ovarian cancer cells expressing the B7-H4 protein, demonstrating antitumor activity in preclinical models with human ovarian tumor xenografts.

However, this therapy also caused delayed and lethal toxicity in mice 6-8 weeks post-treatment, likely due to the widespread expression of B7-H4 in normal tissues, highlighting the need for safety measures in CAR T cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor Regression and Delayed Onset Toxicity Following B7-H4 CAR T Cell Therapy. Smith, JB., Lanitis, E., Dangaj, D., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06305299

Autologous CAR-T Cells Targeting B7H3 in Ovarian ... The purpose of this study is to test the safety and tolerability of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-02577

Chimeric Antigen Receptor (CAR) T-cell Therapy with iC9- ... This phase I trial studies the safety, side effects, and best dose of using autologous T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0171298525000221

Development and evaluation of novel CAR-T Cell therapy The B7-H3-CAR-T cells effectively lysed these tumor cells, as evidenced by a significant decrease in the normalized cell index over time compared to NC-T cells ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12539249/

B7-H3-mediated reversal of CAR-T cell exhaustion induces ... We demonstrated that GPR31-dependent 12-HETE accumulation in the ovarian cancer microenvironment drives CAR-T cell exhaustion via lipid ...

5. trialx.com trialx.com/clinical-trials/listings/302903/autologous-car-t-cells-targeting-b7h3-in-ovarian-cancer-ic9-carb7-h3-t-cells/

Autologous CAR-T Cells Targeting B7H3 in Ovarian ... The purpose of this study is to test the safety and tolerability of using a new treatment called autologous T lymphocyte chimeric antigen ...

6. reporter.nih.gov reporter.nih.gov/search/n25YPDT2X0qT80EgFat2lg/project-details/11009563

Targeting B7-H3 in ovarian cancer - RePORT RePORTER - National ... We have identified B7-H3 (CD276) as a suitable target for chimeric antigen receptor (CAR) T cells in OC. B7-H3 is a tumor-promoting transmembrane protein ...