Article
Author: Joseph, Sujith K ; Brenner, Malcolm K ; Janeway, Katherine A ; Kalra, Mamta ; Zhang, Huimin ; Gad, Ahmed Z ; Navai, Shoba ; Grilley, Bambi ; Heslop, Helen E ; Wu, Mengfen ; Salem, Ahmed Hamed ; Mehta, Birju ; Nawas, Zeid ; Lapteva, Natalia ; Mullikin, Dolores ; Gottschalk, Stephen ; Major, Angela ; Gerken, Claudia ; Wang, Tao ; Hicks, M John ; Robertson, Catherine ; Gee, Adrian ; Thakkar, Sachin G ; Salsman, Vita S ; Sanber, Khaled ; Wels, Winfried S ; Hegde, Meenakshi ; Dotti, Gianpietro ; Shree, Ankita ; Dakhova, Olga ; DeRenzo, Christopher ; Bao, Riyue ; Bhat, Raksha R ; Ahmed, Nabil ; Mathew, Pretty R ; Chakraborty, Rikhia ; Campbell, Matthew
In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 108 T cells per m2 after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 108 CAR+ T cells per m2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1-2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3-4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044 .