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

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ClinicalTrials.gov Identifier: NCT03769467
Recruitment Status : Recruiting
First Posted : December 7, 2018
Last Update Posted : January 10, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Atara Biotherapeutics

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Nasopharyngeal Carcinoma Nasopharyngeal Neoplasms Epstein-Barr Virus Infections Epstein-Barr Viraemia Biological: tabelecleucel Biological: pembrolizumab Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 28, 2018
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: tabelecleucel in combination with pembrolizumab
Tabelecleucel 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.
Biological: tabelecleucel
Tabelecleucel is an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
Other Names:
  • tab-cel®
  • ATA129
  • EBV-CTL

Biological: pembrolizumab
pembrolizumab IV infusion
Other Name: MK-3475




Primary Outcome Measures :
  1. Phase 1b: Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Approximately 1 month ]
  2. Phase 1b: Maximum tolerated dose (MTD) [ Time Frame: Approximately 1 year ]
  3. Phase 1b: Recommended phase 2 dose (RP2D) of tabelecleucel in combination with pembrolizumab [ Time Frame: Approximately 1 year ]
  4. Objective response rate (ORR) [ Time Frame: Approximately 38 months ]
    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 :
  1. Complete Response (CR) rate [ Time Frame: Approximately 38 months ]
  2. Duration of response (DOR) [ Time Frame: Approximately 38 months ]
    DOR is defined as CR + PR

  3. Progression-free survival (PFS) [ Time Frame: Approximately 38 months ]
  4. Overall Survival (OS) [ Time Frame: Approximately 38 months ]
  5. Immune response rate (iRR) [ Time Frame: Approximately 38 months ]
    iRR is defined as immune CR [iCR] + immune PR [iPR] rate

  6. Duration of immune response (DOiR) [ Time Frame: Approximately 38 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03769467


Contacts
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Contact: Atara Biotherapeutics (805) 603-4856 clinicaltrials@atarabio.com
Contact: Atara Biotherapeutics

Locations
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United States, Missouri
Washington University School of Medicine (Adults and Pediatrics) Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Douglas Adkins, MD    314-747-8475    dadkins@wustl.edu   
United States, Pennsylvania
University of Pennsylvania (Adults and Pediatrics) Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Joshua Bauml, MD    215-614-1858    Joshua.Bauml@uphs.upenn.edu   
Sponsors and Collaborators
Atara Biotherapeutics
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Wen Shi, MD, PhD Atara Biotherapeutics
Study Director: Akshay Sudhindra, MD Atara Biotherapeutics

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Responsible Party: Atara Biotherapeutics
ClinicalTrials.gov Identifier: NCT03769467     History of Changes
Other Study ID Numbers: ATA129-NPC-202
KEYNOTE PN597 ( Other Identifier: Merck Sharp & Dohme Corp. )
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Atara Biotherapeutics:
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

Additional relevant MeSH terms:
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Carcinoma
Neoplasms
Virus Diseases
Nasopharyngeal Carcinoma
Viremia
Nasopharyngeal Neoplasms
Epstein-Barr Virus Infections
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Herpesviridae Infections
DNA Virus Infections
Tumor Virus Infections
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents