<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03769467</url>
  </required_header>
  <id_info>
    <org_study_id>ATA129-NPC-202</org_study_id>
    <secondary_id>KEYNOTE PN597</secondary_id>
    <nct_id>NCT03769467</nct_id>
  </id_info>
  <brief_title>Tabelecleucel in Combination With Pembrolizumab in Subjects With Epstein-Barr Virus-associated Nasopharyngeal Carcinoma (EBV+ NPC)</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Atara Biotherapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Atara Biotherapeutics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, open-label, single-arm Phase 1B/2 study to assess the safety and&#xD;
      efficacy of tabelecleucel in combination with pembrolizumab for the treatment of subjects&#xD;
      with platinum-pretreated, recurrent/metastatic Epstein-Barr Virus-associated Nasopharyngeal&#xD;
      Carcinoma (EBV+ NPC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, open-label, single-arm Phase 1B/2 study to assess the safety and&#xD;
      efficacy of tabelecleucel in combination with pembrolizumab for the treatment of subjects&#xD;
      with platinum-pretreated, recurrent/metastatic EBV+ NPC.&#xD;
&#xD;
      Tabelecleucel will be selected for each subject from the bank of available tabelecleucel cell&#xD;
      products based on matching ≥ 2 human leukocyte antigen (HLA) alleles, at least one of which&#xD;
      is a restricting HLA allele, shared between the tabelecleucel donor and the subject's EBV+&#xD;
      NPC. Sites will provide high resolution HLA typing of the subject and other information as&#xD;
      required by the protocol.&#xD;
&#xD;
      Phase 1B will identify the maximum tolerated dose (MTD) and characterize the dose limiting&#xD;
      toxicity (DLT) for tabelecleucel in combination with pembrolizumab in up to 24 subjects. In&#xD;
      the absence of an MTD, the recommended Phase 2 dose (RP2D) will be identified. Phase 2 will&#xD;
      evaluate the safety and efficacy of the combination in 36 subjects at the recommended dose&#xD;
      level from Phase 1B.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Phase 1B part was completed with review of DLTs and cumulative safety data by Safety Data&#xD;
    Review Committee and identification of a safe RP2D. Post-internal review, sponsor decided to&#xD;
    terminate the study, and hence, Phase 2 part was not conducted.&#xD;
  </why_stopped>
  <start_date type="Actual">February 19, 2019</start_date>
  <completion_date type="Actual">August 19, 2021</completion_date>
  <primary_completion_date type="Actual">August 19, 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1B: Incidence of dose-limiting toxicities (DLTs)</measure>
    <time_frame>Within the first 21-day cycle</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1B: Maximum tolerated dose (MTD)</measure>
    <time_frame>Within the first 21-day cycle</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1B: Recommended Phase 2 Dose (RP2D) of tabelecleucel in combination with pembrolizumab</measure>
    <time_frame>Approximately 1 year</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>Approximately 38 months</time_frame>
    <description>The ORR is defined as complete response (CR) or partial response (PR) confirmed &gt;= 28 days from the initial response assessment showing a response.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complete Response (CR) rate</measure>
    <time_frame>Approximately 38 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>Approximately 38 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Approximately 38 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Approximately 38 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune response rate (iRR)</measure>
    <time_frame>Approximately 38 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of immune response (DOiR)</measure>
    <time_frame>Approximately 38 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Nasopharyngeal Carcinoma</condition>
  <condition>Nasopharyngeal Neoplasms</condition>
  <condition>Epstein-Barr Virus Infections</condition>
  <condition>Epstein-Barr Viraemia</condition>
  <condition>Epstein-Barr Virus-associated Nasopharyngeal Carcinoma (EBV+ NPC)</condition>
  <arm_group>
    <arm_group_label>tabelecleucel in combination with pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive IV infusions of tabelecleucel at 2 × 10^6 T-cells/kg on Days 1, 8, and 15; and an IV infusion of pembrolizumab at 200 mg for adults or 2 mg/kg for adolescents on Day 1 of each 21-day cycle (at least 2 cycles or up to 4 cycles). For Cohort 1, if there is a dose-limiting toxicity, the dose of tabelecleucel will be reduced to 1 x 10^6 cells/kg and pembrolizumab will continue to be administered as above. Otherwise, all subjects in Cohort 1 will receive tabelecleucel at 2 x 10^6 cells/kg/dose and pembrolizumab as above. Subjects in Cohort 2 will receive the recommended Phase 2 dose of tabelecleucel per the SDRC and pembrolizumab as above.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>tabelecleucel</intervention_name>
    <description>Tabelecleucel is an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.</description>
    <arm_group_label>tabelecleucel in combination with pembrolizumab</arm_group_label>
    <other_name>tab-cel®</other_name>
    <other_name>ATA129</other_name>
    <other_name>Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pembrolizumab</intervention_name>
    <description>pembrolizumab IV infusion</description>
    <arm_group_label>tabelecleucel in combination with pembrolizumab</arm_group_label>
    <other_name>MK-3475</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female ≥ 12 years of age&#xD;
&#xD;
          2. Incurable, locally recurrent or metastatic Epstein-Barr virus (EBV)+NPC (World Health&#xD;
             Organization type II/III) in whom the EBV nucleic acid or antigens have been&#xD;
             demonstrated in tissue biopsy samples.&#xD;
&#xD;
          3. Subjects must have had prior receipt of platinum-containing regimen either:&#xD;
&#xD;
               1. For the treatment of recurrent or metastatic disease, or&#xD;
&#xD;
               2. Experienced progression of disease within 6 months following completion of a&#xD;
                  platinum-based combination therapy as part of (neo)adjuvant chemotherapy. Note:&#xD;
                  Subject who had only concurrent chemoradiation therapy without (neo)adjuvant&#xD;
                  therapy and then recurred/metastasized must have progressed on at least 1&#xD;
                  platinum-containing regimen for their recurrent/metastatic disease before study&#xD;
                  entry.&#xD;
&#xD;
          4. Phase 1B (Cohort 1):&#xD;
&#xD;
               1. Checkpoint inhibitor naïve (have never received pembrolizumab or any other&#xD;
                  anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX40 or anti-CTLA-4&#xD;
                  antibodies) OR&#xD;
&#xD;
               2. Refractory to an anti-programmed cell death protein-1 (PD-1) or anti-programmed&#xD;
                  death-ligand1 (PD-L1) monoclonal antibody approved by the local regulatory agency&#xD;
                  either as monotherapy or in combination with other checkpoint inhibitors or&#xD;
                  therapies according to their approved label. To be considered refractory to an&#xD;
                  anti-PD-1 or anti-PD-L1 monoclonal antibody, all of the following criteria must&#xD;
                  be met:&#xD;
&#xD;
             i. Received at least 2 doses of anti-PD-1 or anti-PD-L1 monoclonal antibody at a local&#xD;
             regulatory agency-approved dose and schedule. ii. Have progressive disease after&#xD;
             anti-PD-1 or anti-PD-L1 monoclonal antibody as defined according to Response&#xD;
             Evaluation Criteria in Solid Tumors) RECIST 1.1. The initial evidence of progressive&#xD;
             disease is to be confirmed by a second assessment, no less than 4 weeks from the date&#xD;
             of the first documented progressive disease, in the absence of rapid clinical&#xD;
             progression. (The eligibility determination will be made by the investigator and then&#xD;
             the sponsor will collect for retrospective analysis at a central vendor. Once&#xD;
             progressive disease is confirmed, the initial date of progressive disease&#xD;
             documentation will be considered the date of disease progression).&#xD;
&#xD;
             iii. Documented disease progression within 24 weeks of the last dose of anti-PD-1 or&#xD;
             anti-PD-L1 monoclonal antibody. A subject who was re-treated with anti-PD-1 or&#xD;
             anti-PD-L1 monoclonal antibody and a subject who was on maintenance with an anti-PD-1&#xD;
             or anti-PD-L1 monoclonal antibody will be allowed to enter the study as long as there&#xD;
             is documented PD within 24 weeks of the last treatment date (with the anti-PD-1 or&#xD;
             anti-PD-L1 monoclonal antibody).&#xD;
&#xD;
          5. Phase 1B (Cohort 1): If PD-1/PD-L1 failure (ie, refractory to or relapsed after&#xD;
             PD-1/PD-L1 treatment), must have a lesion that can be biopsied after administration of&#xD;
             tabelecleucel with acceptable clinical risk (as judged by the investigator) and must&#xD;
             agree to undergo biopsy before Cycle 1 Day 1.&#xD;
&#xD;
          6. Phase 2 (Cohort 2): Checkpoint inhibitor naïve (have never received pembrolizumab or&#xD;
             any other anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX40 or anti-CTLA-4&#xD;
             antibodies).&#xD;
&#xD;
          7. For all subjects: Agree to submit prior biopsy material, if available, for biomarker&#xD;
             assessment.&#xD;
&#xD;
          8. Life expectancy ≥ 4 months at time of screening.&#xD;
&#xD;
          9. Measurable disease using RECIST 1.1. Tumor lesions situated in a previously irradiated&#xD;
             area are considered measurable if progression has been documented in such lesions.&#xD;
&#xD;
         10. Eastern Cooperative Oncology Group (ECOG) performance status of &lt; 2 for subjects aged&#xD;
             &gt; 16 years; Lansky score ≥ 70 for subjects aged 12 to 16 years.&#xD;
&#xD;
         11. Adequate organ function per the protocol.&#xD;
&#xD;
         12. Willing and able to provide written informed consent (pediatric subjects 12 to &lt; 18&#xD;
             years of age must provide assent along with consent from the subject's legally&#xD;
             authorized representative).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Disease that is suitable for local therapy administered with curative intent&#xD;
&#xD;
          2. Requires vasopressor or ventilator support.&#xD;
&#xD;
          3. Received antithymocyte globulin or similar anti-T-cell antibody therapy ≤ 4 weeks&#xD;
             prior to Cycle 1 Day 1.&#xD;
&#xD;
          4. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other&#xD;
             form of immunosuppressive therapy within 7 days prior to Cycle 1 Day 1 of study&#xD;
             treatment. The use of physiologic doses of corticosteroids may be approved after&#xD;
             consultation with the sponsor's medical monitor.&#xD;
&#xD;
          5. Active autoimmune disease that has required systemic treatment in past 2 years (ie,&#xD;
             with use of disease modifying agents, corticosteroids or immunosuppressive drugs).&#xD;
             Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement&#xD;
             therapy for adrenal or pituitary insufficiency) is not considered a form of systemic&#xD;
             treatment and is allowed.&#xD;
&#xD;
          6. History or evidence of interstitial lung disease.&#xD;
&#xD;
          7. History of severe hypersensitivity (Grade ≥ 3) to pembrolizumab and/or any of its&#xD;
             excipients.&#xD;
&#xD;
          8. Active infection requiring systemic therapy.&#xD;
&#xD;
          9. History of (non-infectious) pneumonitis that required steroids or current pneumonitis.&#xD;
&#xD;
         10. Received transfusion of blood products (including platelets or red blood cells) or&#xD;
             administration of colony stimulating factors (including granulocyte-colony stimulating&#xD;
             factor, granulocyte macrophage-colony stimulating factor or recombinant erythropoetin)&#xD;
             within 4 weeks prior to study Day 1.&#xD;
&#xD;
         11. Unresolved immunotherapy-related AEs or treatment for these events within 4 weeks&#xD;
             prior to enrollment.&#xD;
&#xD;
         12. History of severe immunotherapy-related adverse effects (Common Terminology Criteria&#xD;
             for Adverse Events [CTCAE] grade 4 or CTCAE grade 3 requiring treatment &gt; 4 weeks).&#xD;
&#xD;
         13. Received any non-oncology vaccine therapy used for prevention of infectious diseases&#xD;
             for up to 30 days prior to enrollment. Examples include, but are not limited to:&#xD;
             measures, mumps, rubella, chicken pox, yellow fever, rabies, bacille Calmette-Guerin,&#xD;
             and typhoid vaccine. Seasonal flu vaccines that do not contain live virus are&#xD;
             acceptable.&#xD;
&#xD;
         14. Known additional malignancy that is progressing or requires active treatment.&#xD;
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the&#xD;
             skin that has undergone potentially curative therapy or in situ cervical cancer.&#xD;
&#xD;
         15. Pregnancy or breastfeeding: females of childbearing potential must have a negative&#xD;
             serum pregnancy test. The serum pregnancy must be confirmed negative within 72 hours&#xD;
             of Cycle 1 Day 1 (first dose of investigational product) for the subject to be&#xD;
             eligible.&#xD;
&#xD;
         16. Female of childbearing potential or male with a female partner of childbearing&#xD;
             potential unwilling to use a highly effective method of contraception (abstinence is&#xD;
             acceptable) for the course of the study through 120 days after the last study dose.&#xD;
&#xD;
         17. Inability to comply with study procedures.&#xD;
&#xD;
         18. Received chemotherapy or targeted small molecule therapy within 2 weeks of Cycle 1 Day&#xD;
             1. Subjects must have recovered (ie, grade ≤ 1 or at baseline) from adverse events&#xD;
             (AEs) due to a previously administered agent. Subjects with grade ≤ 2 neuropathy or&#xD;
             grade ≤ 2 alopecia are an exception to this criterion.&#xD;
&#xD;
         19. Received prior radiotherapy within 2 weeks of Cycle 1 Day 1. Subjects must have&#xD;
             recovered from all radiation-related toxicities, not require corticosteroids, and not&#xD;
             have had radiation pneumonitis. A 1- week washout is permitted for palliative&#xD;
             radiation (≤ 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.&#xD;
&#xD;
         20. Antibody/biologic therapy within 4 weeks of Cycle 1 Day 1 or not recovered (i.e.,&#xD;
             grade ≤ 1 or at baseline) from AEs due to agents administered more than 4 weeks&#xD;
             earlier.&#xD;
&#xD;
         21. Carcinomatous meningitis; and/or active CNS metastases, unless metastases are treated&#xD;
             and stable and the subject does not require systemic steroids. NOTE: Subjects with&#xD;
             previously treated brain metastases may participate provided they are stable (without&#xD;
             evidence of progression by imaging [using the identical imaging modality for each&#xD;
             assessment, either magnetic resonance imaging (MRI) or computed tomography (CT) scan]&#xD;
             for at least four weeks prior to the first dose of investigational product and any&#xD;
             neurologic symptoms have returned to baseline), have no evidence of new or enlarging&#xD;
             brain metastases, and are not using steroids for at least 7 days prior to first dose&#xD;
             of investigational product. This exception does not include carcinomatous meningitis&#xD;
             which is excluded regardless of clinical stability.&#xD;
&#xD;
         22. History or current evidence of any condition, therapy, or laboratory abnormality that&#xD;
             might confound the results of the study, interfere with the subject's participation&#xD;
             for the full duration of the study, or is not in the best interest of the subject to&#xD;
             participate, in the opinion of the treating investigator.&#xD;
&#xD;
         23. Known psychiatric or substance abuse disorders that would interfere with cooperation&#xD;
             with the requirements of the study.&#xD;
&#xD;
         24. Known history of human immunodeficiency virus (HIV), known active hepatitis B virus&#xD;
             (HBV; e.g., hepatitis B surface antigen [HBsAg] reactive), or hepatitis C virus (HCV;&#xD;
             e.g., HCV ribonucleic acid [RNA] is detected).&#xD;
&#xD;
         25. Prior treatment with any investigational product within 4 weeks of Cycle 1 Day 1.&#xD;
&#xD;
         26. Prior treatment with EBV T cells.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Willis Navarro, MD</last_name>
    <role>Study Director</role>
    <affiliation>Atara Biotherapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford Hospital and Clinics</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlantic Health System / Morristown Medical Center</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07962</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laura &amp; Isaac Perlmutter Cancer Center at NYU Langone Health</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania (Adults and Pediatrics)</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
  </removed_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <disposition_first_submitted>August 17, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>September 26, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 30, 2022</disposition_first_posted>
  <last_update_submitted>September 26, 2022</last_update_submitted>
  <last_update_submitted_qc>September 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nasopharyngeal Carcinoma (NPC)</keyword>
  <keyword>NPC</keyword>
  <keyword>Nasopharyngeal Cancer</keyword>
  <keyword>Nose Cancer</keyword>
  <keyword>Epstein-Barr Virus (EBV)</keyword>
  <keyword>Epstein-Barr Virus Viremia</keyword>
  <keyword>EBV-associated NPC</keyword>
  <keyword>Allogeneic, off-the-shelf T-cell</keyword>
  <keyword>immunotherapy</keyword>
  <keyword>Head and Neck Cancer</keyword>
  <keyword>Carcinoma</keyword>
  <keyword>Nasopharyngeal Neoplasms</keyword>
  <keyword>Neoplasms, Glandular and Epithelial</keyword>
  <keyword>Neoplasms by Histologic Type</keyword>
  <keyword>Neoplasms</keyword>
  <keyword>Pharyngeal Neoplasms</keyword>
  <keyword>Otorhinolaryngologic Neoplasms</keyword>
  <keyword>Head and Neck Neoplasms</keyword>
  <keyword>Neoplasms by Site</keyword>
  <keyword>Nasopharyngeal Diseases</keyword>
  <keyword>Pharyngeal Diseases</keyword>
  <keyword>Stomatognathic Diseases</keyword>
  <keyword>Otorhinolaryngologic Diseases</keyword>
  <keyword>Pembrolizumab</keyword>
  <keyword>Programmed death-1 (PD-1)</keyword>
  <keyword>Programmed death-ligand 1(PD-L1)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Epstein-Barr Virus Infections</mesh_term>
    <mesh_term>Viremia</mesh_term>
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Nasopharyngeal Carcinoma</mesh_term>
    <mesh_term>Nasopharyngeal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03769467
org study id: ATA129-NPC-202
secondary id: KEYNOTE PN597
nct id: NCT03769467
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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).
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 (RP2D) 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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1B: Incidence of dose-limiting toxicities (DLTs)
time frame: Within the first 21-day cycle
measure: Phase 1B: Maximum tolerated dose (MTD)
time frame: Within the first 21-day cycle
measure: Phase 1B: Recommended Phase 2 Dose (RP2D) of tabelecleucel in combination with pembrolizumab
time frame: Approximately 1 year
measure: Objective response rate (ORR)
time frame: Approximately 38 months
description: The ORR is defined as complete response (CR) or partial response (PR) confirmed >= 28 days from the initial response assessment showing a response.
measure: Complete Response (CR) rate
time frame: Approximately 38 months
measure: Duration of response (DOR)
time frame: Approximately 38 months
measure: Progression-free survival (PFS)
time frame: Approximately 38 months
measure: Overall Survival (OS)
time frame: Approximately 38 months
measure: Immune response rate (iRR)
time frame: Approximately 38 months
measure: Duration of immune response (DOiR)
time frame: Approximately 38 months
arm group label: tabelecleucel in combination with pembrolizumab
arm group type: Experimental
description: Subjects will receive IV infusions of tabelecleucel at 2 × 10^6 T-cells/kg on Days 1, 8, and 15; and an IV infusion of pembrolizumab at 200 mg for adults or 2 mg/kg for adolescents on Day 1 of each 21-day cycle (at least 2 cycles or up to 4 cycles). For Cohort 1, if there is a dose-limiting toxicity, the dose of tabelecleucel will be reduced to 1 x 10^6 cells/kg and pembrolizumab will continue to be administered as above. Otherwise, all subjects in Cohort 1 will receive tabelecleucel at 2 x 10^6 cells/kg/dose and pembrolizumab as above. Subjects in Cohort 2 will receive the recommended Phase 2 dose of tabelecleucel per the SDRC and pembrolizumab as above.
intervention type: Biological
intervention name: tabelecleucel
description: Tabelecleucel is an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
arm group label: tabelecleucel in combination with pembrolizumab
other name: tab-cel®
other name: ATA129
other name: Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL)
intervention type: Biological
intervention name: pembrolizumab
description: pembrolizumab IV infusion
arm group label: tabelecleucel in combination with pembrolizumab
other name: MK-3475
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Willis Navarro, MD
role: Study Director
affiliation: Atara Biotherapeutics
facility: 
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country: United States
country: Canada
responsible party type: Sponsor
mesh term: Virus Diseases
mesh term: Epstein-Barr Virus Infections
mesh term: Viremia
mesh term: Carcinoma
mesh term: Neoplasms
mesh term: Nasopharyngeal Carcinoma
mesh term: Nasopharyngeal Neoplasms
mesh term: Pembrolizumab
sharing ipd: No