On June 15, 2018 Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported positive long-term outcomes including durable remissions and encouraging safety findings from two Phase 2 studies of tab-cel (tabelecleucel), Atara’s most advanced off-the-shelf T-cell immunotherapy (Press release, Atara Biotherapeutics, JUN 15, 2018, View Source [SID1234527345]). These single center, open-label studies enrolled patients with Epstein-Barr virus associated post-transplant lymphoproliferative disorder (EBV+ PTLD) following allogeneic hematopoietic cell transplant (HCT) or solid organ transplant (SOT) who failed first-line therapy. Atara and its collaborating investigators at Memorial Sloan Kettering Cancer Center (MSK) reported the Phase 2 results in a poster presentation at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), being held in Stockholm, Sweden, June 14-17, 2018.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Tab-cel demonstrated durable remissions and an encouraging safety profile after substantial follow-up time for patients with EBV-associated lymphomas who have limited treatment options and often experience poor outcomes," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "No patient who responded to tab‑cel in these studies died of EBV+ PTLD after treatment with this off-the-shelf, allogeneic T-cell immunotherapy. We are progressing two tab-cel Phase 3 clinical studies to confirm the Phase 2 findings in patients with EBV+ PTLD following HCT and SOT who have failed first line therapy."

Overall Survival (OS)

One- and three-year OS for tab-cel treated patients with EBV+ PTLD following HCT who failed rituximab (n=35) was 68% and 55%, respectively. Median OS was not reached after 23.3 months of follow-up in this patient group. The expected median survival for patients with EBV+ PTLD following HCT who have failed rituximab first line therapy is 16 to 56 days.1,2
In patients with EBV+ PTLD following SOT who failed rituximab, the one- and three-year OS after treatment with tab-cel (n=14) was 64% and 43%, respectively. Median survival in this patient group was 21.3 months, which compares favorably to the expected 12- to 13-month median survival in patients with EBV+ PTLD following SOT who fail to achieve a complete response to first-line therapy with single-agent rituximab.3
None of the EBV+ PTLD patients who had complete or partial responses (CR or PR) after treatment with tab-cel died of EBV+ PTLD. Two-year OS for these responding patients was 83% and 86% following HCT (n=24) and SOT (n=7), respectively.
Overall response rates (ORR)

Tab-cel was associated with durable ORR (CR plus PR) of 69% and 50% in patients with EBV+ PTLD following HCT and SOT, respectively, who have failed rituximab.
Safety

Tab-cel was generally well-tolerated. Safety findings were consistent with previous reports of these studies with no new signals noted with additional follow up.
Atara anticipates results from the first tab-cel Phase 3 study and submission of an EU conditional marketing authorization application in the first half of 2019.

Details for the poster presentation at the EHA (Free EHA Whitepaper) Congress are as follows:

Abstract PF401: Long Term Outcomes of Tabelecleucel (Allogeneic Third-Party EBV-Targeted Cytotoxic T Lymphocytes) for Rituximab-Refractory Post-Transplant EBV+ Lymphomas: A Single Center Experience
Session Title: Gene therapy, cellular immunotherapy and vaccination – Clinical
Presentation Date & Time: Friday, June 15; 5:30 p.m. to 7:00 p.m. CEST
Authors:Susan Prockop, Ekaterina Doubrovina, Amy Feng, Guenther Koehne, Parastoo Dahi, Esperanza Papadopoulos, Craig Sauter, Stephanie Suser, Willis Navarro, Akshay Sudhindra, Richard O’Reilly
Location: Poster area, Älvsjö building, Stockholm International Fairs and Congress Centre (Stockholmsmässan)

About EBV+ PTLD
Since its discovery as the first human oncovirus, Epstein-Barr virus (EBV) has been implicated in the development of a wide range of lymphoproliferative disorders, including lymphomas, and other cancers. EBV is widespread in all human populations and persists as a lifelong, asymptomatic infection. In immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplants (HCT) or solid organ transplants (SOT), EBV-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. 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.

About tab-cel (tabelecleucel; formerly known as ATA129)
Atara’s most advanced T-cell immunotherapy in development, tab-cel, is a potential treatment for patients with Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (EBV+ PTLD) who have failed rituximab, as well as other EBV-associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). In February 2015, FDA granted tab-cel Breakthrough Therapy Designation for EBV+ PTLD following allogeneic hematopoietic cell transplant (HCT), and in October 2016, tab-cel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. Atara also received positive regulatory feedback from Health Canada in September 2017 supporting the submission of tab-cel for an expedited approval pathway. 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 is planning a Phase 1/2 study in NPC. Tab-cel is also available to eligible patients with EBV-associated hematologic and solid tumors through an ongoing multicenter expanded access protocol clinical study, positive interim results of which were presented in December 2017 at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.