Developers Resubmit BLA for Tab-Cel in EBV+ Lymphoproliferative Disease

The most recent FDA decision is supported by findings from the phase 3 ALLELE trial, which assessed the investigational therapy in a small cohort of patients with EBV-positive PTLD.

A biologics license application for tabelecleucel (Ebvallo; tab-cel) as a monotherapy for pretreated patients 2 years old and older with Epstein-Barr virus (EBV)–positive post-transplant lymphoproliferative disease (PTLD) has been resubmitted to the FDA, according to a news release from the drug’s developer Atara Biotherapeutics, Inc.1

The decision follows the FDA’s lift of a clinical hold on a new drug application for tab-cel in the same patient population in May 2025.2 Previously, the FDA issued a complete response letter for tab-cel in patients with EBV-positive PTLD in January 2025, but did not identify deficiencies related to the manufacturing, efficacy, or safety of the agent.3

“The BLA resubmission for tab-cel represents the collaborative efforts with our partner, Pierre Fabre Laboratories, to address the third-party manufacturing facility observations outlined in the January 2025 complete response letter,” Cokey Nguyen, president and chief executive officer of Atara, said in the news release on the biologics license application resubmission.1 “We look forward to continued engagement with the FDA throughout its review and with Pierre Fabre Laboratories as they actively prepare for the potential launch of this innovative therapy in the US.”

The most recent FDA decision is supported by findings from the phase 3 ALLELE trial (NCT03394365), which assessed the investigational therapy in a small cohort of patients with EBV-positive PTLD. Findings were previously published in The Lancet Oncology.4 In the study, patients were assessed separately based on transplantation received: hematopoietic stem-cell transplant (HSCT; n = 14) or solid organ transplant (SOT; n = 29).

At a median follow-up of 14.1 months in the HSCT group, the objective response rate (ORR) was 50% (95% CI, 23%-77%) and included 43% of patients achieving a complete response (CR), as well as 7% achieving a partial response (PR). A total of 21% of patients experienced stable disease for a clinical benefit rate (CBR) of 71%. The median time to response was 1.0 months (IQR, 1.0-1.0), and the median duration of response (DOR) was 23.0 months (95% CI, 15.9-not estimable [NE]).

In the SOT cohort, after a median follow-up of 6.0 months, the ORR was 52% (95% CI, 33%-71%), with 21% and 31% having a CR and PR, respectively. A total of 7% of patients experienced stable disease for a CBR of 59%. The respective median time to response and DOR were 1.1 months (IQR, 1.0-3.0) and 15.2 months (95% CI, 1.2-NE).

Patients in the phase 3 study were included in the final analysis if they had received at least 1 dose of study therapy. The median patient age in the HSCT and SOT groups was 51.9 years (range, 21.9-65.1) and 44.4 years (range, 23.8-67.0), respectively. The majority of patients in each arm were White (86% vs 83%) and had an ECOG performance score of 0 or 1 (77% vs 70%). Patients in each arm had high (46% vs 41%) or intermediate (46% vs 48%) PTLD-adapted prognostic indices and diffuse large B-cell lymphoma histology (71% vs 66%).

The primary end point of the study was ORR. Secondary end points included DOR, time to response, and overall survival. Exploratory end points included CBR.

The most common treatment-emergent adverse effects (TEAEs) in the HSCT and SOT cohorts included pyrexia (36% vs 28%) and diarrhea (29% vs 28%). The most common treatment-emergent serious AEs (SAEs) of grade 3 or higher in severity occurred in 57% vs 52% of respective cohorts, as well as 53% of patients overall.

Treatment-related SAEs were observed in 4 patients across cohorts, including 1 event each of grades 3 and 4 in severity. No patients had treatment-related SAEs that resulted in treatment discontinuation. Additionally, fatal treatment-emergent SAEs occurred in 7% and 14% of the HSCT and SOT groups.

References

1. Atara Biotherapeutics provides regulatory and business updates on tabelecleucel (Tab-cel®). News release. Atara Biotherapeutics, Inc. July 14, 2025. Accessed July 15, 2025. https://tinyurl.com/25pxk95y
2. Atara Biotherapeutics provides regulatory updates on EBVALLO (tabelecleucel). News release. Atara Biotherapeutics, Inc. May 5, 2025. Accessed July 15, 2025. https://tinyurl.com/3cekvud5
3. Atara Biotherapeutics provides regulatory and business update on EBVALLOTM (tabelecleucel). News release. Atara Biotherapeutics, Inc. January 16, 2025. Accessed July 15, 2025. https://tinyurl.com/2sutywn9
4. Mahadeo KM, Baiocchi R, Beitinjaneh A, et al. Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial. Lancet Oncol. 2024;25:376-387. doi:10.1016/S1470-2045(23)00649-6