Sequential Infusion of CD146-Targeted and HER2-Targeted CAR T Cells in Patients With Advanced Sarcomas
Trial Parameters
Brief 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 Criteria
Inclusion Criteria: * Expected survival time ≥3 months; * Diagnosis: Histologically or cytologically confirmed sarcoma (soft tissue or bone sarcoma), that is metastatic, locally advanced, or refractory to standard therapy. This may include osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, leiomyosarcoma, or other high-grade sarcomas. Patients must have evidence of measurable disease as per RECIST or applicable criteria. * Prior Treatment: Patients should have received and progressed on or not be candidates for standard first-line treatments. There is no limit on number of prior lines of therapy, but at least one prior systemic therapy for sarcoma is typically required (unless no standard therapy exists for the subtype). A minimum wash-out period (e.g. 2 weeks) from previous treatments (chemotherapy, radiation, or other immunotherapy) is required before lymphodepletion. * Age and Performance Status: Participants age 12 years and older (both adolescent and adult patients are eligible; for m