Phase I study of ATA188, an off-the-shelf, allogeneic Epstein-Barr virus-targeted T-cell immunotherapy for progressive forms of multiple sclerosis

Jonathan Willmer
Atara Biotherapeutics
27
South San Francisco, California, United States

Abstract

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.

Phase I study of ATA188, an off-the-shelf, allogeneic Epstein-Barr virus-targeted T-cell immunotherapy for progressive forms of multiple sclerosis

Pender MP,1 Hodgkinson SJ,2,3 Broadley S,4 Lindsey J,5 Ioannides ZA,1 Bagert B,6 Khanna R,7
Smith C,7 Gamelin L,8 Ye W,8 Willmer J,8 Bar-Or A9
1The University of Queensland, Brisbane, Australia; 2University of New South Wales, Sydney, Australia; 3Liverpool Hospital,
Liverpool, New South Wales, Australia; 4Griffith University, Southport, Australia; 5University of Texas Health Science
Center at Houston, Houston, TX, USA; 6Ochsner Health, New Orleans, LA, USA; 7QIMR Centre for Immunotherapy and
Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Australia; 8Atara Biotherapeutics, South
San Francisco, CA, USA; 9Center for Neuroinflammation and Experimental Therapeutics, and Department of Neurology,
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA