Phase 1b/2 Study To Evaluate AUTO1 CAR T Cells in Relapsed/Refractory Adult B-Cell ALL

AUTO1, an investigational CD19-targeted chimeric antigen receptor (CAR) T-cell therapy, is being evaluated for the treatment of adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).¹

In an open-label, multicenter fashion, the study aims to determine the safety and efficacy of AUTO1 with the coprimary end points of objective response rate (ORR), and the frequency and severity of adverse events (AEs) and serious AEs occurring after AUTO1 infusion.

As phase 2 secondary end points, the study will assess duration of response, progression-free survival, overall survival, the frequency and severity of AE and serious AEs, the incidence of severe hypogammaglobulinemia, the duration of severe hypogammaglobulinemia, and the detection of CAR T cells measured by pathologic complete responses following AUTO1 infusion.

This study follows the phase 1 single-group assignment study (ALLCAR19; NCT02935257), AUTO1 was given as treatment for relapsed or refractory adult B-ALL. Twenty-five patients were included in the study and the population had a median age of 43.5 years. According to findings published in the Journal of Clinical Oncology, the CAR T cells did not lead to ≥ grade 3 cytokine release syndrome, and 15% experienced grade 3 neurotoxicity, but it was resolved to grade 1 within 72 hours.²

Minimal residual disease (MRD) complete responses were observed in 85% of patients at month 1, and 3 of the 17 eligible patients underwent allogenic stem cell transplant while in remission. AUTO1 treatment achieved event-free survival (EFS) rates of 68.3% at 6 months (95% CI, 42.4%-84.4%) and 48.3% at 12 months (95% CI, 23.1%-69.7%).

Overall AUTO1 was tolerable and safe with high rates of remission in relapsed/refractory adult B-ALL, leading investigators to consider CAR T cells as a possible stand-alone treatment for this disease.

In the newer phase 1b/2 study, patients aged 18 years or older will be enrolled. To be eligible, patients must have an ECOG performance status of 0 or 1, and documented CD19 positivity within 1 month of screening. Patients with Philadelphia chromosome-positive ALL are eligible to enroll if they are intolerant to tyrosine kinase inhibitors (TKIs), failed 2 lines of any TKI, or failed 1 line of a second-generation TKI. All patients must also have adequate renal, hepatic, pulmonary, and cardiac function. The study has specific criteria for entry to the phase 1b portion and phase 2 portions.¹

For cohort 1A of the phase 1b trial and cohort 2A of the phase 2 trial, patients must show presence of ≥ 5% blast in the bone marrow at screening. Those enrolling in cohort 1B of the phase 1b trial and cohort 2B of the phase 2 trial are required to be MRD positive.

The trial is recruiting at 16 locations in the United States and 19 other locations in the United Kingdom and Spain.

_References:

_{1. A Study of CD19 Targeted CAR T Cell Therapy in Adult Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia (ALL). Clinicaltrials.gov. Accessed March 25, 2022. https://clinicaltrials.gov/ct2/show/NCT04404660?term=obecabtagene+autoleucel&draw=2&rank=1}

_{2. Immunotherapy for High Risk/Relapsed CD19+ Acute Lymphoblastic Leukaemia, B-cell Non-Hodgkin's Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL)/ Small Lymphocytic Lymphoma (SLL) Using CAR T-cells to Target CD19 (ALLCAR19). Clinicaltrials.gov. Accessed March 25, 2022. https://www.clinicaltrials.gov/ct2/show/NCT02935257}