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

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

NCT ID: NCT06305299

Condition: Ovary Neoplasm
Ovarian Cancer
Epithelial Ovarian Cancer
Recurrent

Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Cyclophosphamide
Fludarabine
Fludarabine phosphate

Conditions: Keywords:
cellular therapy
biologic therapy
Platinum Resistant

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: iC9-CAR.B7-H3 T cells
Description: iC9-CAR.B7-H3 T cells will then be administered intraperitoneally
Arm group label: Chimeric Antigen Receptors

Other name: iC9-CAR.B7-H3 T

Intervention type: Drug
Intervention name: Cyclophosphamide
Description: cyclophosphamide 300 mg/m2 IV will be given.
Arm group label: Chimeric Antigen Receptors

Other name: Cycloblastin

Other name: Endoxan

Other name: Neosar

Other name: Procytox

Other name: Revimmune

Intervention type: Drug
Intervention name: Fludarabine
Description: fludarabine 30 mg/m2 IV will be given.
Arm group label: Chimeric Antigen Receptors

Other name: Fludara

Other name: Fludarabine Phosphate

Summary: 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: 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).

Criteria for eligibility:
Criteria:
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.

Gender: Female

Gender based: Yes

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Lineberger Comprehensive Cancer Center

Address:
City: Chapel Hill
Zip: 27599
Country: United States

Status: Recruiting

Contact:
Last name: Caroline Babinec
Email: Caroline_babinec@med.unc.edu

Investigator:
Last name: Linda Van Le
Email: Principal Investigator

Start date: July 29, 2024

Completion date: March 2026

Lead sponsor:
Agency: UNC Lineberger Comprehensive Cancer Center
Agency class: Other

Source: UNC Lineberger Comprehensive Cancer Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06305299
http://unclineberger.org/patientcare/clinical-trials/clinical-trials