RecruitingPhase 1Phase 2NCT07066982

Sequential Infusion of CD146-Targeted and HER2-Targeted CAR T Cells in Patients With Advanced Sarcomas

A Phase 1/2 Open-Label, Multicenter Trial of Sequential Infusion of CD146-Targeted and HER2-Targeted CAR T Cells in Patients With Advanced Sarcomas

Sponsor

Essen Biotech

Enrollment

60 participants

Start Date

May 29, 2025

Study Type

INTERVENTIONAL

Conditions

Sarcoma Sarcoma, Synovial Sarcoma,Soft Tissue Sarcoma, Kaposi Sarcoma, Ewing Sarcoma of Bone and Connective Tissue Sarcoma Metastatic Sarcomas, Germinoblastic Sarcoma of Bone

Summary

This is an open-label, non-randomized, multicenter Phase 1/2 trial evaluating a dual CAR-T cell therapy targeting CD146 and HER2 in patients with advanced sarcoma. Participants will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by sequential infusion of autologous CD146-specific and HER2-specific CAR-T cells. The Phase 1 portion will employ a dose-escalation design to assess safety and determine the recommended Phase 2 dose, while the Phase 2 expansion will evaluate preliminary efficacy (tumor response and survival outcomes). Approximately 40 patients (children and adults) with relapsed or refractory sarcomas will be enrolled across multiple centers. All participants will be followed for up to 36 months to monitor dose-limiting toxicities, objective response rates, progression-free survival, overall survival, and long-term safety.

Eligibility

Min Age: 21 YearsMax Age: 90 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a new immune cell therapy approach called CAR-T cells — where a patient's own immune cells are genetically modified to attack cancer — in people with advanced sarcoma (a type of cancer in bones or soft tissues) that has not responded to standard treatments. Two different CAR-T cell products targeting two different proteins (CD146 and HER2) are infused sequentially. **You may be eligible if...** - You are 12 years or older (with guardian consent if a minor) - You have a confirmed diagnosis of advanced or metastatic sarcoma (such as osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, or others) - Your cancer has progressed on or you are not a candidate for standard treatment - Your tumor expresses CD146 or HER2 (special proteins the therapy targets) - Your heart, lung, kidney, and blood counts meet requirements **You may NOT be eligible if...** - You have previously received CAR-T cell therapy - You have active uncontrolled infections including HIV, hepatitis B or C - You have serious heart failure or other major uncontrolled medical conditions - You are pregnant or breastfeeding - You have had an organ transplant or bone marrow transplant 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

BIOLOGICALCD146/HER2 CAR-T cells

The intervention in this clinical trial involves a novel approach using CD146/HER2 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. BCMA/GPRC5D Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, CD146/HER-2 CAR T cells, over 10-20 minutes on day 0. Additional Doses: Eligible patients responding well to the initial CD146/HER-2 CAR-T cell infusion without unacceptable side effects and sufficient CAR-T cell availability may receive 2 or 3 additional doses.