Developers Submit BLA for Tabelecleucel in EBV+ Lymphoproliferative Disease

Supporting data for the BLA in this indication partly came from the phase 3 ALLELE study (NCT03394365).

Developers have submitted a biologics license application (BLA) for tabelecleucel (Tab-cel) as a treatment for adult and pediatric patients with Epstein-Barr virus (EBV)–positive post-transplant lymphoproliferative disease (PTLD), according to a press release from Atara Biotherapeutics, Inc.¹

Specifically, the BLA is intended to support the use of tabelecleucel in those who have received at least 1 prior line of therapy. For those with a solid organ transplant, chemotherapy is a suitable type of prior therapy if no contraindications are present.

“The BLA submission for [tabelecleucel] represents a significant moment for Atara, our partner Pierre Fabre, and the broader allogeneic T-cell therapy field, and is a critical step towards our goal of delivering this first-of-its-kind treatment to [patients with EBV-positive PTLD] in the United States,” Pascal Touchon, president and chief executive officer at Atara, said in the press release.¹

Supporting data for the BLA in this indication partly came from the phase 3 ALLELE study (NCT03394365).

According to findings published in Lancet Oncology, the objective response rate (ORR) among patients with a hematopoietic stem cell transplant (HSCT) was 50% (n = 7/14).² Complete responses (CRs) and partial responses (PRs) occurred in 43% (n = 6/14) and 7% (n = 1/14) of patients in this cohort, respectively.

Among patients with a solid organ transplant (SOT), the ORR was 52% (n = 15/29). Additionally, data highlighted a CR rate of 21% (n = 6/29) and a PR rate of 31% (n = 9/29) in this group.

Among all evaluable patients, the ORR was 51% (n = 22/43), the CR rate was 28% (n = 12/43), and the PR rate was 23% (n = 10/43).

Any-grade treatment-emergent adverse effects (TEAEs) in the HSCT and SOT groups, respectively, included disease progression (36% vs 55%), pyrexia (36% vs 28%), and diarrhea (29% vs 28%). Serious grade 3 or higher TEAEs affected 57% and 52% of patients in each respective group. Additionally, 7% and 14% of patients in each cohort had fatal serious TEAEs.

“…Ongoing results from the first global, multicenter, open-label, phase 3 trial of the novel, first-in-class, allogeneic T-cell therapy tabelecleucel show meaningful clinical outcomes and a favorable safety profile in this at-risk population,” the study authors wrote.² “[Tabelecleucel is] a potentially transformative treatment for patients with relapsed or refractory EBV-positive [PTLD] following HSCT or SOT for whom there are no other approved [PTLD] therapies and who would otherwise have dismal outcomes.”

In the open-label ALLELE trial, patients were assigned to receive tabelecleucel intravenously at 2 x 10⁶ cells/kg on days 1, 8, and 15 of every 35-day treatment cycle. Investigators assessed patients for post-treatment survival for a maximum of 5 years.

The trial’s primary end point was ORR. Secondary end points included duration of response, CR rate, PR rate, time to response, overall survival, allograft loss or rejection, and safety.

Patients with biopsy-proven EBV-positive PTLD that was relapsed or refractory to rituximab (Rituxan) following HSCT or SOT were eligible for enrollment on the trial. Having an ECOG performance status of 3 or lower if 16 years and older or a Lansky score of more than 20 if younger than 16 years was another requirement for enrollment. Additional eligibility criteria included having adequate organ function and morphologic remission of the underlying primary disease following allogeneic HSCT.

Those with Burkitt lymphoma, classical Hodgkin lymphoma, or any T-cell lymphoma were ineligible for enrollment on the study.

References

1. Atara Biotherapeutics submits tabelecleucel (Tab-cel®) biologics license application for treatment of Epstein-Barr Virus positive post-transplant lymphoproliferative disease with U.S. FDA. News release. Atara Biotherapeutics, Inc. May 20, 2024. Accessed May 21, 2024. https://tinyurl.com/3yvu6r22
2. 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. Published online January 31, 2024. doi:10.1016/S1470-2045(23)00649-6