Tabelecleucel for Solid Organ Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy

This is a multicenter, open-label, single-arm phase 3 study to assess the efficacy and safety
of tabelecleucel for the treatment of EBV+ PTLD in the setting of SOT after failure of
rituximab or rituximab plus chemotherapy.

Tabelecleucel cell products will be selected for the subject from a bank of available
tabelecleucel cell products based on matching >= 2 human leukocyte antigen (HLA) alleles, at
least one of which is a restricting HLA allele, shared between the tabelecleucel donor and
the subject's EBV+ PTLD.

Subjects will be enrolled into one of two cohorts based on therapy prior to enrollment:
Cohort A, for those who have failed rituximab alone; and Cohort B, for those who have failed
rituximab and have also received chemotherapy for the treatment of PTLD. Study procedures and
product administration will be the same for each cohort.

Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle,
subjects will receive IV tabelecleucel at a dose of 2×10^6 cells/kg on Days 1, 8, and 15,
followed by observation through Day 35.

Inclusion Criteria:

1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of
these

2. A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD with a pathology sample
available for central review

3. Availability of appropriate HLA partially-matched and restricted tabelecleucel cell
product

4. Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score >= 3) systemic disease (using
Lugano Classification response criteria) by positron emission tomography
(PET)-diagnostic computed tomography (CT). For subjects with treated central nervous
system (CNS) disease, a head CT and/or brain/spinal magnetic resonance imaging (MRI)
as clinically appropriate will be required to follow CNS disease response per Lugano
Classification response criteria.

5. Treatment failure of rituximab monotherapy (Cohort A) or rituximab plus any concurrent
or sequentially administered chemotherapy regimen (Cohort B) for treatment of PTLD.
Note: Subjects with CD20 negative disease are eligible to enroll without prior
anti-CD20 therapy after failure of first-line treatment (reduction of
immunosuppression is not considered first-line therapy) and discussion with the
sponsor's medical monitor.

6. Males and females of any age

7. Eastern Cooperative Oncology Group (ECOG) performance status <= 3 for subjects aged >
16 years; Lansky score >= 20 for subjects from birth to 16 years

8. Adequate organ function

1. Absolute neutrophil count >= 1000/μL, with or without cytokine support

2. Platelet count >= 50,000/μL, with or without transfusion or cytokine support

3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total
bilirubin (TBILI) each < 3×ULN; however, ALT, AST, and TBILI each <= 5×ULN is
acceptable if the elevation is considered due to PTLD involvement of the liver.

4. Creatinine < 3×ULN

9. Subject or subject's representative is willing and able to provide written informed
consent

Exclusion Criteria:

1. Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, methotrexate,
or extracorporeal photopheresis

2. Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving treatment
at enrollment

3. Grade >= 2 graft-versus-host disease (GvHD) per the Center for International Blood and
Marrow Transplant Research (CIBMTR) consensus grading system at enrollment

4. Ongoing or recent use of a checkpoint inhibitor agent (eg ipilimumab, pembrolizumab,
nivolumab) within three drug half-lives from the most recent dose to Cycle 1 Day 1

5. Need for vasopressor or ventilatory support

6. Antithymocyte globulin or similar anti-T cell antibody therapy <= 4 weeks prior to
Cycle 1 Day 1

7. Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor
(CAR) T cells directed against B cells within 8 weeks of Cycle 1 Day 1

8. Pregnancy

9. Female of childbearing potential or male with a female partner of childbearing
potential unwilling to use a highly effective method of contraception

10. Inability to comply with study-related procedures