Preliminary safety and efficacy of ATA188, a pre-manufactured, unrelated donor (off-the-shelf, allogeneic) Epstein-Barr virus-targeted T-cell immunotherapy for patients with progressive forms of multiple sclerosis
ECTRIMS Online Library. Pender M. Sep 13, 2019; 278696; P1657
Michael Pender
Michael Pender
Contributions
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Abstract

Abstract: P1657

Type: Poster Sessions

Abstract Category: Poster Session 3

M. Pender1, S. Hodgkinson2, S. Broadley3, J. Lindsey4, Z. Ioannides1, D. Munson5, K. Rasor5, F. Forozan5, P. Foubert5, B. Aftab5, L. Gamelin5, W. Ye5, J. Willmer5, A. Bar-Or6

1University of Queensland, Brisbane, QLD, 2University of New South Wales, Sydney, NSW, 3Griffith University, Southport, NT, Australia, 4University of Texas Health Science Center at Houston, Houston, TX, 5Atara Biotherapeutics, South San Francisco, CA, 61Center for Neuroinflammation and Experimental Therapeutics, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

Introduction: Evidence suggests Epstein-Barr virus (EBV) infection is associated with multiple sclerosis pathogenesis. In patients (pt) with progressive forms of MS (pMS), autologous EBV-specific T cells may prevent progression and improve symptoms (Pender, et al. JCI Insight. 2018).
Objectives: To evaluate ATA188, an off-the-shelf, allogeneic, EBV-targeted T cell immunotherapy comprised of HLA-matched, in vitro-expanded, cytotoxic T lymphocytes in a first-in-human, multicenter, 2-part study in adults with pMS (NCT03283826). Preliminary data are reported.
Methods: Eligible pt (age 18‒< 66) are EBV-seropositive with pMS and an Expanded Disability Status Scale (EDSS) score of 3‒7. Cohorts (cht) 1‒4 (6‒9 pt/cht) receive escalating doses of ATA188. 1° endpoints: safety and identification of the recommended phase 2 dose (RP2D) of ATA188. Efficacy criteria: EDSS, MS Impact Scale-29, Fatigue Severity Scale, and 12-Item MS Walking Scale scores; timed 25-foot walk; 9-hole Peg Test; and visual acuity. A responder (R) has sustained ≥ minimal clinically significant (MCS) improvement from BL in 2 consecutive evaluations on ≥2 efficacy criteria; a partial responder (PR) has ≥ MCS improvement from baseline (BL) in any 1 evaluation on ≥2 efficacy criteria; and a non-responder (NR) has ≥ MCS decline from BL in any 1 evaluation on ≥2 efficacy criteria (if both criteria are met, pt is NR). Plasma inflammatory biomarkers (IL-2, IL-1β, TNF-α, IL-6) are monitored throughout treatment.
Results: As of 27 May 2019, 19 pt (53% male; median age, 56 years) have enrolled (6 in each of cht 1‒3; 1 in cht 4) and received ≥1 dose of ATA188. Treatment-emergent AEs (TEAE) occurred in 63% (12/19) pt and treatment-related AEs (TRAE) in 37% (7/19) pt; 1 pt (cht 2) had a grade ≥ 3 TEAE, and 1 (cht 4) had a serious TRAE. No dose-limiting toxicities or fatal TEAE have been reported. Efficacy data are available for cht 1 and 2: cht 1, 1 R, 1 PR, and 4 NR at 6 months and 1 R, 0 PR, and 1 NR at 12 months; cht 2, 2 R, 4 PR, and 0 NR at 6 months. On measures of disability, 3/6 showed improvement and 3/6 showed decline in cht 1; 4/6 showed improvement and 1/6 showed decline in cht 2. Inflammatory cytokines remained at or near baseline.
Conclusion: Preliminary data indicate ATA188 is well tolerated and improves efficacy measures in adults with pMS, even at lower doses. These results support continuing part 1 to identify RP2D for part 2, (randomized, double-blind, placebo-controlled portion).
Disclosure: Michael P. Pender reports grants from MS Queensland, a research grant from Atara Biotherapeutics, personal consulting fees from Atara Biotherapeutics, travel support from Atara Biotherapeutics, and membership of the Neurology Clinical Advisory Panel of Atara Biotherapeutics.
Suzanne Hodgkinson reports clinical trial support from Atara Biotherapeutics and honoraria for advisory boards from Biogen, Novartis, Merck, Roche and Sanofi.
Simon Broadley reports clinical trial support through Griffith University from Atara Biotherapeutics.
John W. Lindsey reports clinical trial support from Atara Biotherapeutics.
Zara A. Loannides has nothing to disclose.
Blake T. Aftab, Daniel Munson, Kevin Rasor, Farahnaz Forozan, Philippe Foubert, Laurence Gamelin, Amy Feng, and Jonathan Willmer are employees and stockholders of Atara Biotherapeutics.

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