Tab-cel (tabelecleucel)

P1/2, N=12, Terminated, Atara Biotherapeutics | Phase classification: P1b/2 --> P1/2

P3, N=66, Recruiting, Atara Biotherapeutics | Trial primary completion date: Jun 2022 --> Aug 2025

These include immunosuppression reduction, nucleoside analogs, HDAC inhibitors, EBV-specific cytotoxic T-lymphocytes (CTLs), and monoclonal antibodies, such as rituximab. There is currently an open clinic trial combining the use of a HDAC inhibitor, nanatinostat, and ganciclovir to treat refractory/relapsed EBV lymphomas. Another novel therapy includes tabelecleucel, which is an allogenic EBV-directed T-cell immunotherapy that was approved by the European Medicines Agency, but is currently only available in the US for limited use in relapsed or refractory EBV-positive PTLD. Further research is needed to establish EBV monitoring protocols in high-risk populations, such as those with autoimmune disease, cancer, HIV, or receiving immunosuppressive therapy. Additionally, standardized treatments for both the prevention of EBV reactivation in high-risk populations and treatment of EBV reactivation and lymphoproliferation need to be established.

Updated ALLELE P3 data, which included additional pts and longer follow-up, confirm that tab-cel providesconsistent clinically meaningful outcomes, including improved overall ORR, prolonged DOR and OS, and no safety concerns seen with other adoptive T-cell therapies, making it a potentially transformative treatment advance for r/r EBV + PTLD. EBV, Post-transplant lymphoproliferative disorder

The process for generating tab-cel from unrelated donors enriches for known EBV- specific clones and results in a net amplification of EBV-targeted T-cell clonality. Upon activation, tab-cel exhibits a multi-factorial activation profile and demonstrates PF associated with secretion of effector and chemoattractive cytokines. Altogether this multi-omics profiling will facilitate corollaries associated with clinical outcomes.

P2, N=228, Recruiting, Atara Biotherapeutics | Initiation date: Nov 2020 --> Feb 2021

P2, N=228, Ongoing, Atara Biotherapeutics, Inc.

A Phase III study of tab-cel for solid organ or allogeneic hematopoietic cell transplant patients with EBV+ PTLD after failure of rituximab or rituximab plus chemotherapy (NCT03394365) is ongoing. Figure 1. Study design schema