An Open-Label Phase 1B/2 Study to Evaluate the Safety and Efficacy of Tabelecleucel in Combination With Pembrolizumab in Subjects With Platinum-pretreated, Recurrent/Metastatic Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma
This is a multicenter, open-label, single-arm phase 1b/2 study to assess the safety and efficacy of tabelecleucel in combination with pembrolizumab for the treatment of subjects with platinum-pretreated, recurrent/metastatic Epstein-Barr Virus-associated Nasopharyngeal Carcinoma (EBV+ NPC).
Tabelecleucel will be selected for each subject from the 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+ NPC. Sites will provide high resolution HLA typing of the subject and other information as required by the protocol.
Phase 1b will identify the maximum tolerated dose (MTD) and characterize the dose limiting toxicity (DLT) for tabelecleucel in combination with pembrolizumab in up to 24 subjects. In the absence of an MTD, the recommended Phase 2 dose will be identified. Phase 2 will evaluate the safety and efficacy of the combination in 36 subjects at the recommended dose level from Phase 1b.
12 Years and up
Accepting Healthy Volunteers?
1. Male or female ≥ 12 years of age
2. Incurable, locally recurrent or metastatic EBV+NPC (World Health Organization type II/III)
3. Subjects must have had prior receipt of platinum-containing regimen
4. Phase 1B (Cohort 1):
1. Checkpoint inhibitor naïve (have never received pembrolizumab or any other checkpoint/immuno-oncology agents) OR
2. Refractory to an anti-programmed cell death protein-1 (PD-1) or anti-programmed death-ligand1 (PD-L1) monoclonal antibody approved by the local regulatory agency either as monotherapy or in combination with other checkpoint inhibitors or therapies according to their approved label.
5. Phase 2 (Cohort 2): Checkpoint inhibitor naïve (have never received pembrolizumab or any other checkpoint/immuno-oncology agents
6. Life expectancy ≥ 4 months at time of screening
7. Measurable disease using RECIST 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been documented in such lesions
8. Eastern Cooperative Oncology Group (ECOG) performance status of < 2 for subjects aged > 16 years; Lansky score ≥ 70 for subjects aged 12 to 16 years
9. Adequate organ function per the protocol.
10. Willing and able to provide written informed consent (pediatric subjects 12 to < 18 years of age must provide assent along with consent from the subject's legally authorized representative)
1. Disease that is suitable for local therapy administered with curative intent
2. Requires vasopressor or ventilator support
3. Received antithymocyte globulin or similar anti-T-cell antibody therapy ≤ 4 weeks prior to Cycle 1 Day 1
4. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Cycle 1 Day 1 of study treatment.
5. Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
6. History or evidence of interstitial lung disease
7. History of severe hypersensitivity (Grade ≥ 3) to pembrolizumab and/or any of its excipients
8. Active infection requiring systemic therapy
9. History of (non-infectious) pneumonitis that required steroids or current pneumonitis
10. Received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor or recombinant erythropoetin) within 4 weeks prior to study Day 1
11. Received any non-oncology vaccine therapy used for prevention of infectious diseases for up to 30 days prior to enrollment.
12. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
13. Pregnancy or breastfeeding: females of childbearing potential must have a negative serum pregnancy test.
14. Female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception (abstinence is acceptable) for the course of the study through 120 days after the last study dose
15. Inability to comply with study procedures
16. Received chemotherapy or targeted small molecule therapy within 2 weeks of Cycle 1 Day 1. Subjects must have recovered (ie, grade ≤ 1 or at baseline) from AEs due to a previously administered agent. Subjects with grade ≤ 2 neuropathy or grade ≤ 2 alopecia are an exception to this criterion.
17. Received prior radiotherapy within 2 weeks of Cycle 1 Day 1. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1- week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
18. Antibody/biologic therapy within 4 weeks of Cycle 1 Day 1 or not recovered (i.e., grade ≤ 1 or at baseline) from AEs due to agents administered more than 4 weeks earlier
19. Carcinomatous meningitis; and/or active CNS metastases, unless metastases are treated and stable and the subject does not require systemic steroids.
20. Known history of human immunodeficiency virus (HIV), known active hepatitis B virus (HBV; e.g., hepatitis B surface antigen [HBsAg] reactive), or hepatitis C virus (HCV; e.g., HCV ribonucleic acid [RNA] is detected)
21. Prior treatment with any investigational product within 4 weeks of Cycle 1 Day 1
22. Prior treatment with EBV T cells