Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial

期刊论文
发表日期：

2024年4月24日

查看全文

Meenakshi Hegde,
Shoba Navai,
Christopher DeRenzo,
Sujith K. Joseph,
Khaled Sanber,
Mengfen Wu,
Ahmed Z. Gad,
Katherine A. Janeway,
Matthew Campbell,
Dolores Mullikin,
Zeid Nawas,
Catherine Robertson,
Pretty R. Mathew,
Huimin Zhang,
Birju Mehta,
Raksha R. Bhat,
Angela Major,
Ankita Shree,
Claudia Gerken,
Mamta Kalra,
Rikhia Chakraborty,
Sachin G. Thakkar,
Olga Dakhova,
Vita S. Salsman,
Bambi Grilley,
Natalia Lapteva,
Adrian Gee,
Gianpietro Dotti,
Riyue Bao,
Ahmed Hamed Salem,
Tao Wang,
Malcolm K. Brenner,
Helen E. Heslop,
Winfried S. Wels,
M. John Hicks,
Stephen Gottschalk,
Nabil Ahmed

摘要

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.