Phase I study of ATA188, an off-the-shelf, allogeneic Epstein-Barr virus-targeted T-cell immunotherapy for progressive forms of multiple sclerosis
Epstein-Barr virus (EBV) is a necessary risk factor for the development of multiple sclerosis (MS) [Abrahamyan S et al. JNNP 2020]. Early experience with autologous EBV-specific T-cell adoptive immunotherapy proved safe and may offer clinical benefit [Pender MP et al. JCI Insight 2018].
This Phase I study evaluated the safety and potential efficacy of off-the-shelf, allogeneic EBV-targeted T-cell therapy (ATA188) in adults with progressive forms of MS (NCT03283826). In part-1, four cohorts received escalating doses of ATA188 to determine the recommended part-2 dose (RP2D). Patients were followed for 1-year and given the option to participate in a 4-year open label extension (OLE) at the RP2D (cohort-3 dose). In addition to safety, sustained disability improvement (SDI) was assessed [Pender MP et al. EAN 2020].
As of April 2020, 25 patients had received ≥1 dose of ATA188. No grade >3 events, doselimiting toxicities, cytokine release syndrome, graft vs host disease, or infusion reactions were observed and two treatment-emergent serious adverse events were reported: muscle spasticity (grade-2; not treatment related) and MS relapse (grade-3; possibly treatment related). Efficacy endpoints were assessed in cohorts 1–4 at 6- (n=24) and 12-months (n=23). Six patients met SDI criteria at 6-months and 7 patients at 12-months, which was driven by EDSS in all but 2 patients. At both timepoints, a greater proportion of patients achieved SDI at higher doses. In cohorts-1–4, all patients with SDI at 6-months maintained it through 12-months. OLE data were available for 6 patients; 3 had SDI at 6- and 12-months which was maintained at 15-months.
Preliminary data indicate ATA188 is well tolerated. A greater proportion of patients showed SDI at higher doses. Patients achieving SDI at any timepoint maintained it at future timepoints. Based on these data, part-2 of the study has been initiated using the cohort-3 dose.