Autologous HER2-specific CAR T-cells after lymphodepletion for advanced sarcoma – A Phase I trial

In this prospective, interventional phase I study ( NCT00902044 ) for patients with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T-cells (HER2-CART) after lymphodepletion with cyclophosphamide (Cy) +/− fludarabine (Flu): 1×10 8 T-cells/m 2 after Flu (cohort A) or Flu/Cy (cohort B), and 1×10 8 CAR-positive T-cells/m 2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2-CART after lymphodepletion. The determination of antitumor responses was the secondary outcome. Thirteen patients were treated in 14 enrollments with 7 receiving multiple infusions. HER2-CART expanded after 19 of 21 infusions. Nine of 12 patients in cohorts A and B developed grade 1–2 cytokine release syndrome (CRS). Two patients in cohort C experienced dose limiting toxicity with grade 3–4 CRS. Antitumor activity was observed with clinical benefit in 50% of patients treated. Tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and treatment response. Our results affirm HER2 as a CART target and demonstrate the safety of this therapeutic approach in sarcoma.