On December 12, 2022 10:00 Atara Biotherapeutics, a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, reported updated interim analysis and safety results from its Phase 3 multicenter ALLELE study investigating tabelecleucel (tab-cel) for the treatment of relapsed/refractory (r/r) Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD) following solid organ transplant (SOT) or hematopoietic cell transplant (HCT) (Press release, Atara Biotherapeutics, DEC 12, 2022, View Source [SID1234625181]).

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The Phase 3 ALLELE study findings, along with updated efficacy and safety data from two single-center, open-label studies as well as a multicenter expanded access program investigating tab-cel including patients with Epstein-Barr virus positive leiomyosarcomas (EBV+ LMS), were featured among four poster presentations at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place December 10-13, 2022, in New Orleans.

"The updated efficacy and safety results of the Phase 3 ALLELE study including additional patients and longer follow-up are consistent with the transformative potential of tab-cel in EBV+ PTLD patients with no approved treatment options available," said Jakob Dupont, MD, Head of Global Research & Development at Atara. "Similar to EBV+ PTLD, patients with EBV+ LMS face a poor prognosis with limited treatment options, underscoring the significant need for effective and safe new therapeutic options. We report exciting new data that suggest tab-cel may provide a clinical benefit in these hard-to-treat patients with LMS and, together with other EBV-driven diseases like PTLD, represent the potential of tab-cel to transform the lives of thousands of patients across multiple indications and geographies."

In the ongoing Phase 3 ALLELE study, 43 patients — 14 HCT recipients and 29 SOT recipients — were treated with tab-cel and were included in the analysis. Patients received a median of 2 cycles (range: 1-6) of tab-cel. The median age of evaluable patients for both SOT and HCT was 48.5 years (3.2–81.5) who had received a median of 1 (range: 1-5) prior systemic treatments. Responses per clinical and radiographic assessment were measured by independent oncologic response adjudication (IORA) assessment.

Results as of November 2021 data cutoff showed:

An objective response rate (ORR) of 51.2% (22/43) was observed for both HCT and SOT groups (95% CI: 35.5, 66.7), 51.7% (15/29) for patients following SOT (95% CI: 32.5, 70.6) and 50.0% (7/14) for HCT patients (95% CI: 23.0, 77.0) with a best overall response of Complete Response (CR; 27.9%; n=12; n=6, SOT, n=6, HCT) or Partial Response (PR; 23.3%; n=10; n=9, SOT, n=1, HCT).
The median time to response (TTR) in all patients was 1.0 month (range: 0.7-4.7) and median duration of response (DOR) in 22 responders was 23.0 months (95% CI: 6.8, not estimable [NE]), with 12/22 responders having a DOR >6 months.
Median overall survival (OS) of 18.4 months (95% CI: 6.9, NE) in all patients, 16.4 months in SOT (95% CI: 5.0, NE) and not yet reached in HCT (95% CI: 5.7, NE).
One-year survival rates were 61.1% (95% CI: 43.7, 74.5), 56.2% in SOT (95% CI: 34.6, 73.2) and 70.1% in HCT (95% CI: 38.5, 87.6).
Patients responding to tab-cel had longer one-year survival compared to the non-responders, with a one-year survival rate of 84.4% (95% CI: 58.9, 94.7) versus 34.8% (95% CI: 14.6, 56.1) for non-responders.
In addition, Atara presented updated efficacy and safety data investigating the potential of tab-cel in patients with EBV+ LMS who have received at least one therapy. EBV+ LMS is a rare, aggressive, and potentially fatal solid tumor that responds poorly to radiation and chemotherapy. Among 18 patient-treatments, median age was 8.9 years (range: 3–35) and 44.4% of patients were male.

Results showed:

A clinical benefit rate (CR, PR, and stable disease) of 77.8% (14/18) (95% CI: 56.6, 96.2), and ORR of 22.2% (95% CI: 6.4, 47.6; PR in all cases) was observed. Median follow-up for all patients was 18.9 months (95% CI: 1.5, 109.3).
The estimated median OS was 77.4 months (95% CI:18.0, NE) and the median progression-free survival (PFS) was 12.5 months (95% CI: 5.5, NE).
Median DOR was 6.2 months (95% CI: 4.8, NE) with a one-year DOR rate of 37.5% (95% CI: 1.1, 80.8). The one-year survival rate was 86.7% (95% CI: 56.4, 96.5) and the estimated two-year survival rate was 78.0% (95% CI: 45.5, 92.5).
In both the ALLELE and LMS studies, tab-cel was well tolerated and the safety profile consistent with previous data. There was no evidence of tumor flare reaction, infusion reactions, cytokine release syndrome, transmission of infectious diseases, and no events of graft versus host disease (GvHD) or organ rejection related to tab-cel.

In separate posters, Atara also presented the methodology of using T-cell receptor β (TCRβ) sequencing to identify allogeneic cell product clones post-infusion and data confirming the absence of clinical manifestation of immunogenicity following tab-cel administration in patients enrolled in the ALLELE study.

Poster Presentation Details:

Title: New and Updated Results from a Multicenter, Open-Label, Global Phase 3 Study of Tabelecleucel (Tab-cel) for Epstein–Barr Virus-Positive Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) Following Allogeneic Hematopoietic Cell (HCT) or Solid Organ Transplant (SOT) after Failure of Rituximab or Rituximab and Chemotherapy (ALLELE)

Presenting Author: Kris Michael Mahadeo, MD, MPH, MD Anderson Cancer Center, Houston, TX
Date & Time: Monday, December 12, 2022, 6-8 p.m. CST / 5-7 p.m. PST
Abstract Number: 4658
Poster Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster III
Location: Ernest N. Morial Convention Center, Hall D
Title: Updated Efficacy and Safety of Tabelecleucel in Patients with Epstein-Barr Virus-Positive (EBV+) Leiomyosarcomas (LMS)

Presenting Author: Lauren S. Jiménez-Kurlander, MD, Boston Children’s Hospital/Dana Farber Cancer Institute, Boston, MA
Date & Time: Sunday, December 11, 2022, 6-8 p.m. CST / 5-7 p.m. PST
Abstract Number: 3349
Poster Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster II
Location: Ernest N. Morial Convention Center, Hall D
Title: Utilizing TCRseq to Detect Tabelecleucel, an Allogeneic Epstein-Barr Virus (EBV)-Specific T-Cell Therapy, Post-Infusion

Presenting Author: Fiona Ruiz, PhD, Atara Biotherapeutics, Thousand Oaks, CA
Date & Time: Saturday, December 10, 2022, 5:30-7:30 p.m. CST / 4:30-6:30 p.m. PST
Abstract Number: 2169
Poster Session: 803. Emerging Tools, Techniques and Artificial Intelligence in Hematology: Poster I
Location: Ernest N. Morial Convention Center, Hall D
Title: Exploring the Impact of Humoral Immunogenicity with Tabelecleucel for the Treatment of EBV+ PTLD Following HCT and SOT

Presenting Author: Tassja J. Spindler, Atara Biotherapeutics, Thousand Oaks, CA
Date & Time: Sunday, December 11, 2022, 6-8 p.m. CST / 5-7 p.m. PST
Abstract Number: 3351
Poster Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster II
Location: Ernest N. Morial Convention Center, Hall D
About Tabelecleucel

Tabelecleucel (tab‐cel) is an allogeneic, EBV-specific T-cell immunotherapy which targets and eliminates EBV-infected cells in an HLA-restricted manner. Tab-cel has been granted Breakthrough Therapy Designation for the treatment of rituximab-refractory EBV-associated lymphoproliferative disease (LPD) by the U.S. Food and Drug Administration (FDA) and has orphan drug designation in the U.S. Tabelecleucel received PRIME designation by the European Medicines Agency (EMA) for the treatment of patients with EBV-associated PTLD in the allogeneic hematopoietic stem cell transplant (HCT) setting who have failed on rituximab and has orphan drug designation in the EU.