RecruitingPhase 1Phase 2NCT07067255

Sequential CD146 and GPC3 CAR-T Cell Therapy in Advanced Ovarian Cancer

Phase 1/2 Study of Sequential CD146 and GPC3 CAR-T Cell Therapy in Advanced Ovarian Cancer

Sponsor

Essen Biotech

Enrollment

80 participants

Start Date

Apr 29, 2025

Study Type

INTERVENTIONAL

Conditions

Ovarian Cancer Ovarian Carcinoma Ovarian Cancer Stage IV Ovarian Sarcoma

Summary

This is a multicenter, open-label Phase 1/2 clinical trial evaluating the safety and preliminary efficacy of sequentially administered CD146-targeted and GPC3-targeted CAR-T cell therapy in patients with advanced relapsed or refractory ovarian cancer. Eligible patients will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by an infusion of autologous CD146-directed CAR-T cells (Arm A) and a subsequent infusion of autologous GPC3-directed CAR-T cells (Arm B). The Phase 1 portion will assess safety, tolerability, and dose-limiting toxicities (DLTs) to determine a recommended Phase 2 dose, while the Phase 2 portion will evaluate efficacy endpoints including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Patients will be followed for up to 36 months after CAR-T infusion to monitor long-term outcomes and adverse events.

Eligibility

Min Age: 21 YearsMax Age: 90 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a sequential CAR-T cell therapy in women with advanced ovarian cancer that has come back or stopped responding to standard treatment. The approach involves infusing two sets of genetically engineered immune cells — one targeting a protein called CD146 and another targeting GPC3 — one after the other. **You may be eligible if...** - You are 18 or older with confirmed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer - Your cancer has relapsed or is resistant to platinum-based chemotherapy - Your tumor tests positive for both CD146 and GPC3 - You have measurable disease on imaging and are in good physical condition - Your organs and blood counts meet acceptable thresholds **You may NOT be eligible if...** - You have previously received CAR-T cell therapy targeting CD146 or GPC3 - You have active cancer in the brain (CNS metastases) - You have active hepatitis B or C, or uncontrolled HIV - You are pregnant or breastfeeding - You have a serious heart condition or another active cancer requiring treatment Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

BIOLOGICALGPC3 CD146 CAR-T cells

The intervention in this clinical trial involves a novel approach using CD146/GPC3 Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies. Treatment Regimen: Patients in the trial will undergo the following regimen: Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy. Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2. GPC3/CD146 Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, GPC3/CD146 CAR T cells, over 10-20 minutes on day 0. Additional Doses: Eligible patients responding well to the initial CD146/GPC3 CAR-T cell infusion without unacceptable side effects and sufficient CAR-T cell availability may receive 2 or 3 additional doses.