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.