Brief Title
Tabelecleucel in Combination With Pembrolizumab in Subjects With 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
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).
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Phase 1b: Incidence of dose-limiting toxicities (DLTs)
Secondary Outcome
Complete Response (CR) rate
Condition
Nasopharyngeal Carcinoma
Intervention
tabelecleucel
Study Arms / Comparison Groups
tabelecleucel in combination with pembrolizumab
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
60
Start Date
November 28, 2018
Completion Date
September 2023
Primary Completion Date
September 2023
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 adverse events
(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
Gender
All
Ages
12 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Patrick Phuong, PharmD, 650-491-5794, [email protected]
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT03769467
Organization ID
ATA129-NPC-202
Secondary IDs
KEYNOTE PN597
Responsible Party
Sponsor
Study Sponsor
Atara Biotherapeutics
Collaborators
Merck Sharp & Dohme Corp.
Study Sponsor
Patrick Phuong, PharmD, Study Director, Atara Biotherapeutics
Verification Date
November 2019