NCT06305299

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

Administration of T Cells Expressing B7-H3 Specific Chimeric Antigen Receptors (CAR) and Containing the Inducible Caspase 9 Safety Switch in Subjects With Recurrent Platinum Resistant Epithelial Ovarian Cancer

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Conditions

• Ovary Neoplasm
• Ovarian Cancer
• Epithelial Ovarian Cancer
• Recurrent

Interventions

Type	Name	Description
BIOLOGICAL	iC9-CAR.B7-H3 T cells	iC9-CAR.B7-H3 T cells will then be administered intraperitoneally
DRUG	Cyclophosphamide	cyclophosphamide 300 mg/m2 IV will be given.
DRUG	Fludarabine	fludarabine 30 mg/m2 IV will be given.

Timeline

• Start date: 2024-07-29
• Primary completion: 2036-04-01
• Completion: 2036-04-01
• First posted: 2024-03-12
• Last updated: 2026-04-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study