Tabelecleucel in Combination With Pembrolizumab in Subjects With Epstein-Barr Virus-associated Nasopharyngeal Carcinoma (EBV+ NPC)

Not Recruiting

Trial ID: NCT03769467


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).

Official Title

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

Stanford Investigator(s)

Parveen Shiraz, MD
Parveen Shiraz, MD

Instructor, Medicine - Blood & Marrow Transplantation

A. Dimitrios Colevas, MD
A. Dimitrios Colevas, MD

Professor of Medicine (Oncology) and, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS) and of Radiation Oncology (Radiation Therapy)


Inclusion Criteria:

   1. Male or female ≥ 12 years of age

   2. Incurable, locally recurrent or metastatic Epstein-Barr virus (EBV)+NPC (World Health
   Organization type II/III) in whom the EBV nucleic acid or antigens have been
   demonstrated in tissue biopsy samples.

   3. Subjects must have had prior receipt of platinum-containing regimen either:

      1. For the treatment of recurrent or metastatic disease, or

      2. Experienced progression of disease within 6 months following completion of a
      platinum-based combination therapy as part of (neo)adjuvant chemotherapy. Note:
      Subject who had only concurrent chemoradiation therapy without (neo)adjuvant
      therapy and then recurred/metastasized must have progressed on at least 1
      platinum-containing regimen for their recurrent/metastatic disease before study

   4. Phase 1B (Cohort 1):

      1. Checkpoint inhibitor naïve (have never received pembrolizumab or any other
      anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX40 or anti-CTLA-4
      antibodies) 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. To be considered refractory to an
      anti-PD-1 or anti-PD-L1 monoclonal antibody, all of the following criteria must
      be met:

   i. Received at least 2 doses of anti-PD-1 or anti-PD-L1 monoclonal antibody at a local
   regulatory agency-approved dose and schedule. ii. Have progressive disease after
   anti-PD-1 or anti-PD-L1 monoclonal antibody as defined according to Response
   Evaluation Criteria in Solid Tumors) RECIST 1.1. The initial evidence of progressive
   disease is to be confirmed by a second assessment, no less than 4 weeks from the date
   of the first documented progressive disease, in the absence of rapid clinical
   progression. (The eligibility determination will be made by the investigator and then
   the sponsor will collect for retrospective analysis at a central vendor. Once
   progressive disease is confirmed, the initial date of progressive disease
   documentation will be considered the date of disease progression).

   iii. Documented disease progression within 24 weeks of the last dose of anti-PD-1 or
   anti-PD-L1 monoclonal antibody. A subject who was re-treated with anti-PD-1 or
   anti-PD-L1 monoclonal antibody and a subject who was on maintenance with an anti-PD-1
   or anti-PD-L1 monoclonal antibody will be allowed to enter the study as long as there
   is documented PD within 24 weeks of the last treatment date (with the anti-PD-1 or
   anti-PD-L1 monoclonal antibody).

   5. Phase 1B (Cohort 1): If PD-1/PD-L1 failure (ie, refractory to or relapsed after
   PD-1/PD-L1 treatment), must have a lesion that can be biopsied after administration of
   tabelecleucel with acceptable clinical risk (as judged by the investigator) and must
   agree to undergo biopsy before Cycle 1 Day 1.

   6. Phase 2 (Cohort 2): Checkpoint inhibitor naïve (have never received pembrolizumab or
   any other anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX40 or anti-CTLA-4

   7. For all subjects: Agree to submit prior biopsy material, if available, for biomarker

   8. Life expectancy ≥ 4 months at time of screening.

   9. 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.

10. Eastern Cooperative Oncology Group (ECOG) performance status of < 2 for subjects aged
   > 16 years; Lansky score ≥ 70 for subjects aged 12 to 16 years.

11. Adequate organ function per the protocol.

12. 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).

Exclusion Criteria:

   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. The use of physiologic doses of corticosteroids may be approved after
   consultation with the sponsor's medical monitor.

   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

   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. Unresolved immunotherapy-related AEs or treatment for these events within 4 weeks
   prior to enrollment.

12. History of severe immunotherapy-related adverse effects (Common Terminology Criteria
   for Adverse Events [CTCAE] grade 4 or CTCAE grade 3 requiring treatment > 4 weeks).

13. Received any non-oncology vaccine therapy used for prevention of infectious diseases
   for up to 30 days prior to enrollment. Examples include, but are not limited to:
   measures, mumps, rubella, chicken pox, yellow fever, rabies, bacille Calmette-Guerin,
   and typhoid vaccine. Seasonal flu vaccines that do not contain live virus are

14. 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.

15. Pregnancy or breastfeeding: females of childbearing potential must have a negative
   serum pregnancy test. The serum pregnancy must be confirmed negative within 72 hours
   of Cycle 1 Day 1 (first dose of investigational product) for the subject to be

16. 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.

17. Inability to comply with study procedures.

18. 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 adverse events
   (AEs) due to a previously administered agent. Subjects with grade ≤ 2 neuropathy or
   grade ≤ 2 alopecia are an exception to this criterion.

19. 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.

20. 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

21. Carcinomatous meningitis; and/or active CNS metastases, unless metastases are treated
   and stable and the subject does not require systemic steroids. NOTE: Subjects with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging [using the identical imaging modality for each
   assessment, either magnetic resonance imaging (MRI) or computed tomography (CT) scan]
   for at least four weeks prior to the first dose of investigational product and any
   neurologic symptoms have returned to baseline), have no evidence of new or enlarging
   brain metastases, and are not using steroids for at least 7 days prior to first dose
   of investigational product. This exception does not include carcinomatous meningitis
   which is excluded regardless of clinical stability.

22. History or current evidence of any condition, therapy, or laboratory abnormality that
   might confound the results of the study, interfere with the subject's participation
   for the full duration of the study, or is not in the best interest of the subject to
   participate, in the opinion of the treating investigator.

23. Known psychiatric or substance abuse disorders that would interfere with cooperation
   with the requirements of the study.

24. 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).

25. Prior treatment with any investigational product within 4 weeks of Cycle 1 Day 1.

26. Prior treatment with EBV T cells.


biological: tabelecleucel

biological: pembrolizumab

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Elizabeth Winters

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