Neoplasms

All Conditions

Infections

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Symptoms and General Pathology

Musculoskeletal Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Nasopharyngeal Neoplasms

Recurrence

Communicable Diseases

Head and Neck Neoplasms

Epstein-Barr Virus Infections

Death

Virus Diseases

Nasopharyngeal Carcinoma

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Pharyngeal Neoplasms

Viremia

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pharyngeal Diseases

Otorhinolaryngologic Neoplasms

Nose Neoplasms

Nasopharyngeal Diseases

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Syndrome

Systemic Inflammatory Response Syndrome

Inflammation

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

Tabelecleucel is an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.

tabelecleucel

pembrolizumab

Willis Navarro, MD

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.

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

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

The ORR is defined as complete response (CR) or partial response (PR) confirmed \>= 28 days from the initial response assessment showing a response.

Merck Sharp & Dohme LLC

Atara Biotherapeutics

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Post-transplant Lymphoproliferative Disease

Antirheumatic Agents

Hematinics

Gastrointestinal Agents

Rituximab

Liver Extracts

Pancrelipase

Pancreatin

Participants who have failed rituximab will receive IV tabelecleucel.

Participants who have failed both rituximab and chemotherapy will receive IV tabelecleucel.

Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.

Aditi Mehta, DO

Amandeep Salhotra, MD

Huynh Cao, MD

Neena Kapoor, MD

Herbert Eradat, MD

William Asch, MD

Udeme Ekong, MD

Amer Beitinjaneh, MD, MPH, MSc

Suhag Parikh, MD

Jean Koff, MD

Sonali Chaudhury, MD

Satayaijt Kosuri, MD

Patrick Hagen, MD

Jean Yared, MD

Sarah Nikiforow, MD

Armin Ghobadi, MD

Koen Van Besien, MD

Ran Reshef, MD

Kevin Curran, MD

Michael Kent, MD

Matthew McKinney, MD

Hanna Rabi, MD

Robert Baiocchi, MD, PhD

Nemecek Eneida, MD

Nancy Bunin, MD

Michelle Hudspeth, MD

Bhagirathbhai Dholaria, MD

Luis Pineiro, MD

Tamra Slone, MD

Kris Michael Mahadeo, MD

James Butterworth, MD

Shyam Panicker, MD, MBBS, MRCP, FRACP, FRCPA

Daniel Chambers, MBBS, MRCP, FRACP, MD

Devendra Hiwase, MD

Rachel Conyers, MD, MBBS, FRACP

Duncan Purtill, MD, MBBS, FRACP, FRCPA

Nina Worel, MD

Willems Evelyne, MD

Daan Dierickx, MD

Victor Lewis, MD

Joerg Krueger, MD

Arjun Law, MD

Edouard Forcade, MD

Eolia Brissot, MD

Franck Morschhauser, MD

Benedicte Neven, MD

Sylvain Choquet, MD

Roberto Cairoli, MD

Patrizia Comoli, MD

Simona Sica, MD

Franco Locatelli, MD

Giaccone Luisa, MD

Eva González-Barca, MD

Lucrecia Yanez, MD

Pere Barba, MD

Gillen Oarbeascoa, MD

Jose Perez-Simon, MD

Juan Montoro, MD

Sridhar Chaganti, MD

Daniele Avenoso, MD

Eduardo Olavarria, MD

The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

This is a multicenter, open-label, phase 3 study to assess the efficacy and safety of tabelecleucel for the treatment of EBV+ PTLD in the setting of SOT after failure of rituximab and rituximab plus chemotherapy (SOT cohort) or HCT after failure of rituximab (HCT cohort).

Enrollment will be preceded by confirmation of availability of partially human leukocyte antigen (HLA) matched and restricted tabelecleucel for the participant.

Study procedures and product administration will be the same for each cohort. Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle, participants will receive intravenous tabelecleucel at a dose of 2×10\^6 cells/kg on Days 1, 8, and 15, followed by observation through Day 35. Treatment will continue until maximal response, unacceptable toxicity, initiation of non protocol therapy, or failure of tabelecleucel with up to 2 different HLA restrictions (SOT cohort) or up to 4 different HLA restrictions (HCT cohort). The study includes a total of 5 years of follow-up for disease and survival status.

This protocol has been amended to include the HCT cohort from clinical study ATA129-EBV-301 (NCT03392142).

NOTE, 29 April 2020: Enrollment is temporarily paused at study site/locations with status "active, not recruiting" due to COVID-19 restrictions.

Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy

Multicenter, Open-Label, Phase 3 Study of Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab or Rituximab and Chemotherapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tabelecleucel in Combination With Pembrolizumab in Subjects With Epstein-Barr Virus-associated Nasopharyngeal Carcinoma (EBV+ NPC)	NCT03769467	Nasopharyngeal ... Nasopharyngeal ... Epstein-Barr Vi... Epstein-Barr Vi... Epstein-Barr Vi...	tabelecleucel pembrolizumab	12 Years -	Atara Biotherapeutics
Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy	NCT03394365	Epstein-Barr Vi... Solid Organ Tra... Lymphoprolifera... Allogeneic Hema... Stem Cell Trans...	tabelecleucel	-	Atara Biotherapeutics
Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy	NCT03394365	Epstein-Barr Vi... Solid Organ Tra... Lymphoprolifera... Allogeneic Hema... Stem Cell Trans...	tabelecleucel	-	Atara Biotherapeutics
Tabelecleucel in Combination With Pembrolizumab in Subjects With Epstein-Barr Virus-associated Nasopharyngeal Carcinoma (EBV+ NPC)	NCT03769467	Nasopharyngeal ... Nasopharyngeal ... Epstein-Barr Vi... Epstein-Barr Vi... Epstein-Barr Vi...	tabelecleucel pembrolizumab	12 Years -	Atara Biotherapeutics

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