Hung Trinh, Senior VP of Operations at Seneca Therapeutics, shared a post on LinkedIn about a recent article by Fabian Müller et al, published in Nature Medicine:
“CD19 CAR-T cells for treatment-refractory autoimmune diseases: the phase 1/2 CASTLE basket trial
- The median transduction efficacy was 34% (IQR 30−37) with CD4+ cells dominating the product over CD8+ T cells, leading to a CD4/CD8 ratio of 2.9
- CAR-T cells were no longer detected after a median of 83 (56−113) days
- B cell depletion and effects on white blood cells
- B cells were rapidly depleted in all patients after a median time of 7 (0−7) days
Innovative trial designs are needed to allow feasible testing of the safety and efficacy of CAR-T cells in clinical studies. CASTLE (CAR-T cells in systemic B cell mediated autoimmune disease) is a phase 1/2a two-stage optimal design basket study that investigated the safety and efficacy of zorpocabtagene autoleucel (Zorpo-cel, also known as MB-CART19.1), an autologous CD19 CAR-T cell product, in patients with treatment-resistant systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM).
The primary safety outcome was the rate of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The secondary clinical efficacy outcomes were remission of SLE according to DORIS criteria, no progression of interstitial lung disease in SSc and American College of Rheumatology (ACR) major/moderate response in IIM after 24 weeks. A total of 24 patients were enrolled (10 with SLE, 9 with SSc and 5 with IIM), all receiving a single infusion of Zorpo-cel after stopping immunosuppressive treatments and receiving standard lymphodepletion with cyclophosphamide and fludarabine. Primary and secondary endpoints of CASTLE were met.
Regarding safety, no CRS higher than grade 2 and no ICANS occurred. Regarding efficacy, 22 of the 24 patients achieved predefined efficacy endpoints, with 9 out of 10 patients with SLE reaching DORIS remission, 9 out of 9 patients with SSc showing no disease progression, and 4 out of 5 patients with IIM reaching ACR major/moderate response. Furthermore, all patients remained free of glucocorticoids and any other immunosuppressive treatment over the entire observation period of 24 weeks. CASTLE suggests the feasibility, safety and efficacy of Zorpo-cel in three different autoimmune diseases and paves the way for conducting a pivotal study.”
Title: CD19 CAR-T cells for treatment-refractory autoimmune diseases: the phase 1/2 CASTLE basket trial
Authors: Fabian Müller, Melanie Hagen, Andreas Wirsching, Soraya Kharboutli, Michael Aigner, Simon Völkl, Sascha Kretschmann, Koray Tascilar, Jule Taubmann, Laura Bucci, Maria Gabriella Raimondo, Christina Bergmann, Tobias Rothe, Giulia Corte, Carlo Tur, Luis Muñoz, Sebastian Böltz, Louis Schuster, Fabian Hartmann, Panagiotis Garantziotis, Silvia Spörl, Ingrid Vasova, Armin Gerbitz, Bernd Spriewald, Hans Kiener, Diana Giannarelli, Franco Locatelli, Maria-Antonietta D’Agostino, Linda Hanssens, Stefan Miltenyi, Aline Bozec, Ricardo Grieshaber-Bouyer, Andreas Mackensen, Georg Schett
Read the Full Article on Nature Medicine
More post featuring Hung Trinh.