Autologous CAR-T Cells Targeting B7H3 in Ovarian Cancer iC9-CAR.B7-H3 T Cells

NCT ID: NCT06305299

Last Updated: 2025-09-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-29

Study Completion Date

2026-03-31

Brief Summary

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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 against the B7-H3 antigen (iC9-CAR.B7-H3 T cells) in patients with ovarian cancer 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. The study team wants to know how much (dose) of the iC9-CAR.B7-H3 T cells are safe to use in patients without causing too many side effects and what is the maximum dose could be tolerated.

There are two parts to this study. In part 1, approximately blood will be collected from subjects to prepare the iC9.CAR.B7-H3 T cells. The study team will collect disease-fighting T cells from the blood and modify them to prepare the iC9.CAR.B7-H3 T cells. In part 2, the iC9.CAR.B7-H3 T cells will be given to eligible subjects by infusion three days after completion of lymphodepletion chemotherapy.

Detailed Description

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This phase 1, single-center, open-label study to determine the safety of escalating dosing of chimeric antigen receptor T (CAR-T) cells targeting the B7-H3 antigen and containing the inducible caspase 9 safety switch (iC9-CAR.B7-H3 T cells) administered to adult subjects with relapsed or refractory platinum-resistant epithelial ovarian cancer. The safety of iC9-CAR.B7-H3 T cells administered intraperitoneally via a port/catheter will be investigated using a modified 3+3 design with a starting dose of 1 ×106. The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided on based on the maximum tolerated dose (MTD) and additional factors such as the ability to manufacture sufficient cells for infusion. Additional subjects will be enrolled in an expansion cohort at the recommended phase 2 dose.

Subjects will receive standard-of-care therapy e.g., chemotherapy or radiation therapy to stabilize their disease if the treating physician feels it is in the subject's best interests before the cell therapy.

Subjects with ≥ grade 4 Cytokine Release Syndrome (CRS) or Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) or grade 3 CRS or ICANS that do not improve to grade 0-1 within 72 hours will be given a 0.4mg/kg of rimiducid. Furthermore, subjects who experience a ≥ Grade 3 non-hematologic or hematologic toxicity (Excluding Grade 3 electrolyte abnormalities, hyperglycemia, diarrhea, or nausea and vomiting and Grade 3-4 hematologic toxicity without functional sequelae that do not persist at Grade 3-5 for \> 7 days) felt to be secondary to iC9-CAR.B7-H3 may be given rimiducid (0.4 mg/kg).

Conditions

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Ovary Neoplasm Ovarian Cancer Epithelial Ovarian Cancer Recurrent

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Chimeric Antigen Receptors

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.

Group Type EXPERIMENTAL

iC9-CAR.B7-H3 T cells

Intervention Type BIOLOGICAL

iC9-CAR.B7-H3 T cells will then be administered intraperitoneally

Cyclophosphamide

Intervention Type DRUG

cyclophosphamide 300 mg/m2 IV will be given.

Fludarabine

Intervention Type DRUG

fludarabine 30 mg/m2 IV will be given.

Interventions

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iC9-CAR.B7-H3 T cells

iC9-CAR.B7-H3 T cells will then be administered intraperitoneally

Intervention Type BIOLOGICAL

Cyclophosphamide

cyclophosphamide 300 mg/m2 IV will be given.

Intervention Type DRUG

Fludarabine

fludarabine 30 mg/m2 IV will be given.

Intervention Type DRUG

Other Intervention Names

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iC9-CAR.B7-H3 T Cycloblastin Endoxan Neosar Procytox Revimmune Fludara Fludarabine Phosphate

Eligibility Criteria

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Inclusion Criteria

1. Unless otherwise noted, subjects must meet all of the following criteria to participate in all phases of the study:
2. 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.
3. Age ≥ 18 years at the time of consent.
4. Eastern Cooperative Oncology Group (ECOG) of 0-2.
5. The subject must have histologically or cytologically confirmed epithelial ovarian, peritoneal or fallopian tube cancer and must have a histological diagnosis of a high-grade serous histology based on local histopathological findings.
6. Subject must have recurrent platinum-resistant or platinum-refractory disease defined as: A disease that has progressed by imagining while receiving platinum OR Disease that has recurred within 6 months of the last receipt of platinum-based chemotherapy. Rising CA-125 only is not considered as platinum-resistant or refractory disease.
7. Having received at least 2 prior regimens (including front-line therapy).

Exclusion Criteria

1. Subjects with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
2. The subject is not willing and not able to comply with study procedures based on the judgment of the investigator or protocol designee.

10\. The subject is not willing to undergo a biopsy prior to treatment, after infusion, and at the time of disease progression ), and the tumor is determined to be safe by the treating investigator for biopsy collection.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Linda Van Le, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

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Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Catherine Cheng

Role: CONTACT

919-445-4208

Caroline Babinec

Role: CONTACT

Facility Contacts

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Caroline Babinec

Role: primary

Related Links

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http://unclineberger.org/patientcare/clinical-trials/clinical-trials

University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Other Identifiers

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LCCC2152-ATL

Identifier Type: -

Identifier Source: org_study_id

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