Abstract CT105: AUTO1, a novel fast off CD19CAR delivers durable remissions and prolonged CAR T cell persistence with low CRS or neurotoxicity in adult ALL

• Published in: Cancer research (Chicago, Ill.) Ill.), 2019-07, Vol.79 (13_Supplement), p.CT105-CT105
• Main Authors: Roddie, Claire, O'Reilly, Maeve A., Pinto, Juliana Dias Alves, Vispute, Ketki, Syed, Fahetullah, Nickolay, Lauren, Pathak, Yashma, Gali, Alexia, Lowe, Helen, Champion, Kim, Wheeler, Graham, Olejnik, Jo, Marzolini, Maria, Pule, Martin A., Peggs, Karl S.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2019-CT105

Introduction: CD19 CAR T therapy has advanced treatment of relapsed/refractory (r/r) Acute Lymphoblastic Leukemia (B-ALL). However, several challenges remain including: (1) considerable toxicity of CD19 CAR therapy; (2) the need for long-term persistence to deliver sustained response; (3) requirement for robust, cost effective manufacture. All current CD19 CARs for B-ALL use a high affinity CD19 binder, fmc63. We hypothesized that a CD19 binder with a lower affinity due to a fast binding off-rate, would result in more physiological T-cell activation, reduce toxicity and improve engraftment. Preliminary pediatric clinical data of a novel CD19 CAR (AUTO1) supports this assertion. In adults, prognosis for B-ALL is poor, patients are more vulnerable to CD19 CAR immunotoxicity and there is currently no CD19 CAR therapeutic with acceptable toxicity and durable efficacy. AUTO1 may be particularly well suited to this patient group. We describe preliminary data testing AUTO1 in adults with r/r B-ALL. Further, to address large-scale manufacture, we compare standard manufacturing with a closed semi-automated manufacture process. Methods: Manufacturing: AUTO1 utilizes non-mobilized autologous leucapheresate. The first 6 trial products were generated using a standard dynal bead/WAVE Bioreactor process and subsequent products using a closed CliniMACS® Prodigy/ TransACTTM process. Study design: ALLCAR19 (NCT02935257) is a phase I/II study recruiting subjects 16-65y with r/r B ALL. Lymphodepletion with fludarabine (30 mg/m2 x3) and cyclophosphamide (60mg/kg x1) is followed by split dose CAR T infusion (Day 0: if ≥20% BM blasts, infuse 10 x 106 CAR T; if