Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial.
Nat Cancer
; 5(6): 880-894, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38658775
ABSTRACT
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 .
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sarcoma
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Immunotherapy, Adoptive
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Receptor, ErbB-2
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Receptors, Chimeric Antigen
Limits:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Nat Cancer
Year:
2024
Document type:
Article