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

Sponsor
Essen Biotech
Study ID
NCT07066982
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

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

Eligibility Criteria

Sex
ALL
Age
21 Years - 90 Years
Healthy Volunteers
Not accepted

Interventions

  • CD146/HER2 CAR-T cells — BIOLOGICAL
    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.

Study Details

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.

Key Dates

First listed
Jul 15, 2025
Start date
May 29, 2025
Status verified
Jul 2025
Primary completion
Dec 10, 2027
Completion
Dec 28, 2028

Study Design

Enrollment
60 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: CD146/HER2 CAR T cells, chemotherapy
    Patients will be administered fludarabine phosphate intravenously (IV) over a 30-minute period on days -4 to -2. Additionally, cyclophosphamide will be administered intravenously (IV) over 60 minutes on day -2. Subsequently, patients will receive CD146 HER-2 CAR T cells intravenously (IV) over a duration of 10-20 minutes on day 0. Patients who exhibit positive responses to the initial dose of CD146/HER2 CAR T cells, do not experience unacceptable side effects, and have a sufficient quantity of cells available may be eligible to receive 2 or 3 additional doses of CD146/HER2 CAR T cells.

Primary Outcome Measure

Incidence and severity of dose-limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/BCMA chimeric antigen receptor (CAR) T cells [ Time Frame: 28 days ]

Central Contacts

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