Abstract LB-147: Administration of HER2-CAR T cells after lymphodepletion safely improves T cell expansion and induces clinical responses in patients with advanced sarcomas
Abstract
Background: Patients with advanced sarcoma have limited treatment options and poor survival. In our phase 1 dose-escalation trial, intravenous administration of up to 1x108/m2autologous HER2-CAR T cells in patients with HER2+ sarcoma was safe. The goal of the current study is to evaluate if lymphodepleting chemotherapy can safely improve the expansion of HER2-CAR T cells. Methods: In a phase 1 clinical trial, NCT00902044, we administered 1x108/m2autologous HER2-CAR T cells to patients with recurrent/refractory HER2+ sarcoma following lymphodepletion. Results: Ten patients with refractory/metastatic HER2+ sarcoma (5 osteosarcoma, 3 rhabdomyosarcoma [RMS], 1 Ewing sarcoma, 1 synovial sarcoma) with a median age of 14 (range: 4 to 54) were treated; one RMS patient was re-enrolled and retreated. Each patient received up to 3 infusions of 1x108cells/m2 CAR T cells after lymphodepletion with either fludarabine (Flu; n = 3) or Flu and cyclophosphamide (Flu/Cy; n = 8). Eligible patients were given up to an additional 5 subsequent infusions without lymphodepletion. Flu and Flu/Cy induced lymphopenia with an absolute lymphocyte count of Conclusions: Administration of lymphodepletion chemotherapy followed by autologous HER2-CAR T cells is safely tolerated and is associated with objective clinical benefit in some patients with advanced HER2+ sarcoma. Immune correlative studies suggest that the HER2-CAR T cells given in combination with Flu/Cy lymphodepletion induce endogenous immune…
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