A Study to Evaluate Tabelecleucel in Participants With Epstein Barr Virus (EBV) Associated Diseases

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 [cohort closed for enrollment after completion of stage1]

- EBV+ post-transplant 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 which occurs at 12 (± 1) months after Cycle 1 Day 1

for adults, and 24 (± 1) months after Cycle 1 Day 1 for pediatric participants.

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 relevant 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.