Clinical Trials /

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

NCT03769467

Description:

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).

Related Conditions:
  • Nasopharyngeal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tabelecleucel in Combination With Pembrolizumab in Subjects With EBV+ Nasopharyngeal Carcinoma (ATA129-NPC-202)
  • 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

Clinical Trial IDs

  • ORG STUDY ID: ATA129-NPC-202
  • SECONDARY ID: KEYNOTE PN597
  • NCT ID: NCT03769467

Conditions

  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms
  • Epstein-Barr Virus Infections
  • Epstein-Barr Viraemia

Interventions

DrugSynonymsArms
tabelecleuceltab-cel®, ATA129, EBV-CTLtabelecleucel in combination with pembrolizumab
pembrolizumabMK-3475tabelecleucel in combination with pembrolizumab

Purpose

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).

Detailed Description

      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 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.
    

Trial Arms

NameTypeDescriptionInterventions
tabelecleucel in combination with pembrolizumabExperimentalTabelecleucel will be administered initially to 12 subjects at a dose of 2 x 10^6 cells/kg intravenously (IV) on Day 1, Day 8, and 15 of a 21-day cycle. Pembrolizumab will be administered to adult subjects at 200 mg or to pediatric subjects (12 to < 18 years of age) at 2 mg/kg IV every 3 weeks.
  • tabelecleucel
  • pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          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)

        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.

          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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b: Incidence of dose-limiting toxicities (DLTs)
Time Frame:Approximately 1 month
Safety Issue:
Description:The ORR is defined as complete response [CR] or partial response [PR] confirmed ≥ 28 days from the initial response assessment showing a response.

Secondary Outcome Measures

Measure:Complete Response (CR) rate
Time Frame:Approximately 38 months
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:Approximately 38 months
Safety Issue:
Description:DOR is defined as CR + PR
Measure:Progression-free survival (PFS)
Time Frame:Approximately 38 months
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Approximately 38 months
Safety Issue:
Description:
Measure:Immune response rate (iRR)
Time Frame:Approximately 38 months
Safety Issue:
Description:iRR is defined as immune CR [iCR] + immune PR [iPR] rate
Measure:Duration of immune response (DOiR)
Time Frame:Approximately 38 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Atara Biotherapeutics

Trial Keywords

  • Nasopharyngeal Carcinoma (NPC)
  • NPC
  • Nasopharyngeal Cancer
  • Nose Cancer
  • Epstein-Barr Virus
  • Epstein-Barr Virus Viremia
  • EBV-associated NPC
  • Allogeneic, off-the-shelf T-cell
  • immunotherapy
  • Head and Neck Cancer
  • Carcinoma
  • Nasopharyngeal Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Neoplasms by Histologic Type
  • Neoplasms
  • Pharyngeal Neoplasms
  • Otorhinolaryngologic Neoplasms
  • Head and Neck Neoplasms
  • Neoplasms by Site
  • Nasopharyngeal Diseases
  • Pharyngeal Diseases
  • Stomatognathic Diseases
  • Otorhinolaryngologic Diseases
  • Pembrolizumab
  • PD-1
  • PD1
  • PD-L1
  • PDL1

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