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Tabelecleucel, tab-cel® – Investigational PTLD T-cell immunotherapy

 

Publications and Presentations
Ongoing Clinical Studies

Tabelecleucel, tab-cel® is an off-the-shelf, allogeneic T-cell immunotherapy in Phase 3 studies for patients with EBV+ PTLD (Epstein-Barr virus associated post-transplant lymphoproliferative disease), as well as other EBV-associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). PTLD is a type of cancer or lymphoma that may occur after bone marrow or organ transplant.

In February 2015, the FDA granted tabelecleucel Breakthrough Therapy Designation for Epstein-Barr virus associated post-transplant lymphoproliferative disorder following allogeneic hematopoietic cell transplant (HCT), and in October 2016, tabelecleucel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. In addition, tab-cel® has orphan status in the U.S. and EU.

Tab-cel® is in Phase 3 clinical development for the treatment of EBV+ PTLD following an allogeneic hematopoietic cell transplant (MATCH study) or solid organ transplant (ALLELE study), and Atara recently initiated a Phase 1/2 study in NPC. Tab-cel® is also available to eligible patients with Epstein-Barr virus-associated diseases and malignancies for whom there are no other appropriate therapeutic options through an expanded access program.

If you are interested in learning more about our ongoing clinical studies, please contact us at ClinicalStudies@atarabio.com.

Post-Transplant Lymphoproliferative Disease (PTLD)

Post-transplant lymphoproliferative disease (PTLD) is a type of cancer or lymphoma that may occur after bone marrow or organ transplant.

A patient who receives a transplant must take medications to suppress their immune system (immunosuppression) so that their body will not reject the new bone marrow or organ. When the immune system is suppressed, it is easier to become sick. Sometimes when a transplant patient is infected with Epstein-Barr virus (EBV), the virus may cause a serious cancer or lymphoma known as PTLD.

EBV is a common virus that infects over 90% of people in the world. For most healthy people, it causes common cold like symptoms and then stays in your body but is completely controlled by your immune system, so you don’t have any further symptoms after the initial infection. If a person has a suppressed immune system, the EBV can activate and cause an uncontrolled growth of cells in the patient’s lymph nodes and other organs. When abnormal cells multiply out of control, it may result in cancer.

PTLD is a common cancer after transplant but is still considered a rare disease that only occurs in a small percentage of transplant patients. Rates of PTLD cancer are higher for people who have types of bone marrow and organ transplants that require higher levels of immunosuppression.

In immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplants (HCT) or solid organ transplants (SOT), Epstein-Barr virus associated post-transplant lymphoproliferative disorder (EBV+ PTLD), represents a life-threatening condition.

  • Median overall survival in patients with EBV+ PTLD following HCT who have failed rituximab-based first line therapy is 16-56 days.(1)
  • In EBV+ PTLD following SOT, patients failing rituximab experience increased chemotherapy-induced treatment-related mortality compared to other lymphoma patients. One- and two-year survival in patients with high-risk EBV+ PTLD following SOT is 36% and 0%, respectively.

Nasopharyngeal Carcinoma (NPC)

Nasopharyngeal carcinoma (NPC) is a head and neck cancer that is primarily EBV-associated with worldwide incidence of approximately 80,000 new cases per year. Approximately 25% of patients with NPC develop recurrent or metastatic disease. A majority of NPCs are associated with Epstein-Barr virus (EBV), and upregulation of programmed cell death-ligand 1 (PD-L1) expression upon EBV infection is thought to play a role in the pathogenesis of NPC.

Despite improvements in first-and second-line treatments, metastatic NPC has a poor prognosis with a median overall survival (OS) of 21–29 months.(2) The anti-PD1 checkpoint immunotherapy, pembrolizumab, demonstrated anti-tumor activity in a phase 1b study of patients with recurrent or metastatic NPC, with an objective response rate (ORR) of 26% and median OS of 16.5 months.(3) In a phase 2 study of patients with recurrent or metastatic EBV+ NPC, tabelecleucel, Atara’s off-the-shelf, allogeneic T-cell immunotherapy had a favorable safety profile with an overall response rate of 21% and a 2-year OS rate of 84%.(4)

We initiated a Phase 1/2 study of tab-cel® (tabelecleucel) in combination with Merck’s anti-PD-1 (programmed death receptor-1) checkpoint immunotherapy, KEYTRUDA® (pembrolizumab), in patients with platinum-resistant or recurrent EBV associated NPC.

 

(1) Expected median survival for patients with EBV+ PTLD following HCT who have failed rituximab first line therapy is 16 to 56 days; Atara estimated 1-year survival based on analysis of Ocheni S, et al. EBV reactivation and post transplant lymphoproliferative disorders following allogeneic SCT. Bone Marrow Transplantation. 2008 Aug;42(3):181-6; Fox CP, et al. EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: Clinical features, viral load correlates and prognostic factors in the rituximab era. Bone Marrow Transplant. 2014;49(2):280-6.

(2)Zhang, et al. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016;388:1883-92.

(3)Hsu C, et al. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056.

(4)Prockop, S. et al. Treatment of EBV+ nasopharyngeal carcinoma with banked EBV-specific cytotoxic T cells. J Clin Oncol. 2016;34 (suppl; abstr 3012).