An Open-label, Single-arm, Multicohort, Phase 2 Study to Assess the Efficacy and Safety of Tabelecleucel in Subjects With Epstein-Barr Virus-associated Diseases (EBVision)

More details:

Overview

Tabelecleucel (Ebvallo) is a donor-derived T-cell therapy for relapsed or refractory Epstein–Barr virus–positive post-transplant lymphoproliferative disease (EBV+ PTLD). It is authorised in the European Union for patients aged 2 years and older who have received prior treatment; it remains investigational in the United States. (ema.europa.eu)

Mechanism of action

The therapy contains T cells selected for their ability to recognise Epstein–Barr virus (EBV). Their receptors recognise viral peptides displayed with specific human leukocyte antigen (HLA) molecules on infected cells, enabling the T cells to kill those cells. A product lot is selected according to the patient’s HLA profile; the T cells are not genetically modified. (ema.europa.eu)

Efficacy

In the single-arm phase 3 ALLELE trial, a peer-reviewed analysis of 43 treated patients reported an objective response in 7 of 14 (50%) recipients of a hematopoietic cell transplant and 15 of 29 (52%) recipients of a solid-organ transplant. A subsequent conference abstract covering 75 patients reported an overall response rate of 50.7% (38/75), including 28.0% complete responses; median response duration was 23 months. Because ALLELE has no randomised control group, these results do not establish how much benefit tabelecleucel provides relative to other care. (pubmed.ncbi.nlm.nih.gov)

Safety

In the 75-patient update, serious adverse events occurring after treatment were reported in approximately 63% of patients, and fatal adverse events in approximately 19%; none of the fatal events was judged treatment-related. The investigators reported no cytokine-release syndrome or treatment-related graft-versus-host disease or organ rejection. These findings need to be interpreted in the context of a small trial involving seriously ill patients. (ash.confex.com)

Further reading

• Peer-reviewed ALLELE trial report
• Updated ALLELE conference abstract
• European Medicines Agency product information

Last updated: Sep 2026

Inclusion Criteria:

* Diagnosis of EBV+ disorder.

* Eastern Cooperative Oncology Group performance status ≤ 3 for participants aged ≥ 16 years; Lansky score ≥ 20 for participants from ≥ 1 year to \< 16 years.

* Adequate organ function test results, unless organ dysfunction is considered to be due to the underlying EBV-associated disease by the investigator.

Cohort-specific Inclusion Criteria:

* For participants with PID LPD:

* R/R or newly diagnosed PID LPD for whom. the standard first-line therapy is inappropriate, as determined by investigator. The LPD is confirmed by at least biopsy-proven EBV+ LPD or positive cerebrospinal fluid (CSF) cytology with or without radiographically measurable intracranial disease with EBV detected in CSF.

* Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification (Cheson BD, et al. J Clin Oncol. 2014;27:3059) during or after treatment or failure to achieve a complete response (CR) or partial response (PR) (defined by Lugano radiographic criteria) after standard first-line therapy.

* Participant may have systemic disease only, systemic and CNS disease, or CNS disease only.

* For participants with AID LPD:

* R/R or newly diagnosed AID LPD for whom the standard first line therapy is inappropriate, as determined by the investigator. The LPD is confirmed by at least biopsy-proven EBV+ LPD or positive CSF cytology, with or without radiographically measurable intracranial disease, with EBV detected in CSF.

* Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification during or after treatment or failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy.

* Participant may have systemic disease only, systemic and CNS disease, or CNS disease only.

* For participants with AID etiology or AID attributable to immunosenescence, objective laboratory evidence of immunodeficiency.

* For participants with CNS PTLD:

* R/R or newly diagnosed EBV+ CNS PTLD for whom the standard. first-line therapy is inappropriate, as determined by the investigator. The CNS PTLD is histologically confirmed by at least biopsy-proven EBV+ CNS PTLD or positive CSF cytology with or without radiographically measurable intracranial disease with EBV detected in CSF.

* Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification during or after treatment or failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy.

* Participant may have systemic and CNS disease or CNS disease only.

* For participants with EBV+ 1L PTLD, including CD20-negative disease:

* Biopsy-proven EBV+ PTLD for whom standard first-line therapy (rituximab and/or chemotherapy) is inappropriate, as determined by the investigator.

* Participants must have systemic disease measurable per Lugano Classification criteria, except when contraindicated or mandated by local practice, then MRI may be used.

* For participants with sarcoma, including LMS, or smooth muscle tumors:

* EBV+ sarcoma or smooth muscle tumor with rapidly progressive disease defined as progressive disease per RECIST 1.1 criteria as documented radiographically within a 6-month interval prior to enrollment.

* Participants with newly diagnosed EBV+ sarcoma for whom the standard first-line therapy is inappropriate, as determined by the investigator.

* Biopsy-proven EBV+ sarcoma meeting one of the criteria's of pathologically confirmed EBV+ Leiomyosarcoma or EBV+ sarcoma or smooth muscle tumor.

* Measurable disease using diagnostic CT and/or MRI following RECIST 1.1 criteria (Eisenhauer et al. 2009. Eur J Cancer 45\[2\]:228-247).

Exclusion Criteria:

* Currently active Burkitt, T-cell, natural killer/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy.

* Serious known active infections, defined as ongoing uncontrolled adenovirus infection or infections requiring systemic therapy at the time of enrollment, or known history of human immunodeficiency virus (HIV) infection.

* Suspected or confirmed Grade ≥ 2 acute graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research (CIBMTR) consensus grading system or extensive chronic GvHD per National Institutes of Health (NIH) consensus criteria at the time of the enrollment.

* Need for vasopressor or ventilatory support at the time of enrollment.

* Prior therapy (in order of increasing washout period) prior to enrollment as follows:

* Within 4 weeks or 5 half-lives (whichever is shorter) for any investigational product and/ or any chemotherapy (systemic or intrathecal), targeted small molecule therapy, or antibody/biologic therapy. Note: prior anti-CD20 antibody use is permitted within the washout period if a subsequent disease response assessment indicates disease progression.

* Within 8 weeks: prior tabelecleucel (\> 8 weeks prior to enrollment) is permitted if response was obtained or if usual protocol-directed therapeutic options were not exhausted, for cellular therapies (chimeric antigen receptor therapies directed at T-cells or T-cell subsets, donor lymphocyte infusion, other CTLs or virus-specific T-cells); and/or therapies which could impact tabelecleucel function (anti-thymocyte globulin, alemtuzumab).

* Any prior treatment with EBV-CTLs with the exception of tabelecleucel as above

* Women who are breastfeeding or pregnant.

* Unwilling to comply with protocol specified contraceptive/reproductive restrictions from enrollment through 90 days after the last treatment.

* Ongoing need for daily steroids of \> 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis (for participants with CNS disease, protocol-specified dexamethasone is permitted and concludes by the time of enrollment).

* Any conditions that may put the study outcomes at undue risk (life expectancy \< 60 days or any life-threatening illness, medical condition, or organ system dysfunction).

* For participants with PID LPD or AID LPD: history of prior allogeneic HCT or solid organ transplant.

* For participants with EBV+ 1L PTLD: prior systemic therapy for PTLD.