A Study to Evaluate Tabelecleucel in Participants With Epstein-barr Virus-associated Diseases

Summary

Objectives

This is a multicenter, multicohort, open-label, single-arm, Phase 2 study to assess the
efficacy and safety of tabelecleucel for the treatment of EBV-associated diseases.
Participants will be enrolled in one of the following cohorts:

- EBV+ lymphoproliferative disease (LPD) in the setting of primary immunodeficiency (PID)
(EBV+ PID LPD) that is relapsed and/or refractory (R/R) or newly diagnosed where
standard first-line therapy is inappropriate

- EBV+ LPD in the setting of acquired (non-congenital) immunodeficiency (AID) (EBV+ AID
LPD) that is R/R or newly diagnosed where standard first-line therapy is inappropriate

- EBV+ posttransplant lymphoproliferative disease (PTLD) involving the central nervous
system (CNS) (EBV+ CNS PTLD) that is R/R or newly diagnosed where standard first-line
therapy is inappropriate

- EBV+ PTLD where standard first-line therapy (rituximab or chemotherapy) is
inappropriate, including cluster of differentiation antigen 20 (CD20)-negative disease

- EBV+ sarcomas, including leiomyosarcoma (LMS), or smooth muscle tumors that is rapidly
progressive where standard first-line therapy is inappropriate

Tabelecleucel will be administered in cycles lasting for 35 days. During each cycle,
participants will receive tabelecleucel at a dose of 2 x 10^6 cells/kg intravenously (IV)
weekly for 3 weeks, followed by observation through Day 35. Treatment will continue until
maximal response, disease progression, unacceptable toxicity, or initiation of nonprotocol
therapy for the underlying disease. For EBV+ sarcoma cohort, treatment will continue until
disease progression, unacceptable toxicity, two consecutive complete responses (CRs), or up
to 12 months from the first dose. Participants who fail to respond to initial tabelecleucel
treatment may continue tabelecleucel with a different human leukocyte antigen (HLA)
restriction (termed a Restriction Switch), if available; administration of tabelecleucel with
up to four different HLA restrictions is allowed for any participant.

After treatment is completed or discontinued, participants will complete a safety follow-up
visit at 30 days after the last dose and then will enter a quarterly follow-up period.
Participants without documented disease progression will be assessed every 3 months after the
safety follow-up visit for continued evaluation of disease response until the end of study
(EOS) visit at 24-month after first dose. Participants with disease progression any time
prior to the EOS visit will continue to be followed every 3 months for survival status until
the EOS visit.

An adaptive 2-stage design will be used for each cohort in this study. For each cohort, 8
evaluable participants will be enrolled in Stage 1. The decision to move to Stage 2
enrollment will be based on an interim analysis of the first 8 evaluable participants in the
cohort using investigator's assessment (per defined radiologic, clinical, and/or laboratory
response criteria) who receive tabelecleucel and have at least 1 valid postbaseline disease
response assessment. The number of participants enrolled in Stage 2 for each cohort will
depend on the number of observed responders in Stage 1. Sponsor may decide not to move
forward to Stage 2 in any cohort even if the criteria to move forward for that cohort are
met. The decision not to move forward may also be based on data from one or other cohorts.