49O - Clinical Experience of Tabelecleucel in Epstein-Barr Virus-Positive Post-transplant Lymphoproliferative Disease (EBV+ PTLD) Involving the Central Nervous System

Background

Tabelecleucel is an investigational, off-the-shelf, allogeneic EBV-specific T-cell immunotherapy being studied in patients (pts) with EBV⁺ diseases, including EBV⁺ PTLD with central nervous system (CNS) involvement. Pts with relapsed/refractory (R/R) EBV⁺ CNS PTLD have very limited treatment options and poor prognosis. We previously reported results from pts with R/R EBV⁺ CNS PTLD treated within 2 single-center studies. We report here a combined analysis from 4 open-label studies.

Methods

Safety and efficacy were evaluated using data from 4 open-label studies: 2 single-center, phase 2 (P2) trials (NCT00002663, n=10; NCT01498484, n=2), a multicenter, expanded-access protocol (EAP-201 [2016-2020]; NCT02822495, n=2) and the multicenter, P2 EBVision (study 205) trial (NCT04554914, n=4). Pts with R/R or treatment naive EBV⁺ CNS PTLD received cycles of 3 weekly infusions of tabelecleucel at ∼2x10⁶ cells/kg. Response was assessed by study investigator. Key endpoints were objective response rate (ORR), overall survival (OS), and safety parameters.

Results

Eighteen pts were included in this pooled analysis. Pts received a median (range) of 1 (0 to 5) lines of prior therapy. In all pts, ORR was 77.8% (95% CI: 52.4, 93.6), 1 yr and 2 yr OS rates were 70.6% and 54.9%, respectively (Table). There were no treatment-related fatal or life-threatening treatment-emergent adverse events (TEAEs) reported or serious treatment-related TEAEs of neurotoxicity, organ rejection, GVHD, or tumor flare reaction of any grade. Table: 49O

Key efficacy outcomes in EBV+ CNS PTLD pts treated with tabelecleucel

CI = confidence interval; NE = not estimable; ORR = objective response rate; OS = overall survival.

Conclusions

In this combined analysis that includes the 1^st reported EBVision data, tabelecleucel induced a high response rate of ∼78% and demonstrated promising survival among pts with EBV⁺ CNS PTLD, consistent with previous single-center experience. Tabelecleucel was also well tolerated. The P2 EBVision trial is ongoing to further investigate the clinical benefit of tabelecleucel in pts with EBV⁺ diseases.

Clinical trial identification

NCT00002663, NCT01498484, NCT02822495, NCT04554914.

Editorial acknowledgement

Medical writing assistance was provided by Tricia Gallagher from AMICULUM Ltd.

Legal entity responsible for the study

Atara Biotherapeutics, Inc.

Funding

Atara Biotherapeutics, Inc.

Disclosure

R. Baiocchi: Financial Interests, Personal, Advisory Board: Atara Biotherapeutics, Prelude Therapeutics, Viracta Therapeutics; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultant: Atara Biotherapeutics, Viracta Therapeutics; Financial Interests, Personal, Research Funding, Funding received 2021-2022: Codiak Biosciences; Financial Interests, Personal, Other, Editorial Board: eLife Journal; Other, Personal, Other, Product development, no funding, supply of drug (vaccine): Agenus; Financial Interests, Personal, Research Funding: Prelude Therapeutics; Financial Interests, Personal, Stocks/Shares, Stockholder: Viracta Therapeutics. S. Choquet: Financial Interests, Personal, Other, Consultant: Atara Biotherapeutics, AbbVie, Accord Healthcare, AstraZeneca, Biogaran, Gilead/Kite, Janssen, Pierre Fabre, Roche, Sandoz/Novartis, Takeda, Viatris. M. Ghosh: Non-Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Novartis, Miltenyi, Atara, Cargo Therapeutics; Non-Financial Interests, Personal and Institutional, Advisory Role: Cabaletta Bio; Non-Financial Interests, Personal and Institutional, Local PI: Kite/Gilead. R. Dinavahi, J. Wahlstrom, X. You, S. Zhang: Financial Interests, Personal, Full or part-time Employment: Atara Biotherapeutics; Financial Interests, Personal, Stocks/Shares: Atara Biotherapeutics. S. Prockop: Non-Financial Interests, Institutional, Other, Susan Prockop is a co-inventor of intellectual property licensed to Atara and has transferred her rights to this intellectual property to MSK and has no personal financial interests in Atara Biotherapeutics; Financial Interests, Institutional, Research Funding: Atara Biotherapeutics, Jasper Therapeutics, Allovir; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultant: CellEvolve, Pierre Fabre; Financial Interests, Personal, Other, Honorarium: Regeneron. All other authors have declared no conflicts of interest.