Orca-T Gains FDA Approval in Matched Donor Transplants

Allogeneic regulatory T cell-based immunotherapy with hematopoietic stem and progenitor cell (HSPC) and T cells-vldq (Orca-T; Tregzi) has gained FDA approval for use in matched donor hematopoietic stem cell transplantation (HSCT) with a myeloablative preparative regimen for the treatment hematopoietic and immunologic reconstitution and to improve chronic graft-vs-host disease (cGHVD)-free survival in the treatment of adults with hematological malignancies including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndromes (MDS).¹

Approval for the immunotherapy was based on positive results from the pivotal phase 3 Precision-T trial (NCT04013685), a randomized, open-label multi-center study that evaluated the safety, efficacy and tolerability of Orca-T compared with conventional allogeneic hematopoietic stem cell transplant (alloHSCT) in 187 patients with AML, ALL and MDS.² The study met its primary end point of a statistically significant improvement in survival free moderate-to-severe cGvHD with Orca-T vs alloHSCT.

In the trial, investigators reported that the 1-year moderate-to-severe cGVHD-free survival rate was 78% (95% CI, 65%-87%) in the Orca-T arm (n = 93) vs 38% (95% CI, 26%-51%) in the alloHSCT arm (HR, 0.26; P < .00001). The cumulative incidence of moderate-to-severe cGVHD was 13% (95% CI, 5%-23%) with Orca-T vs 44% (95% CI, 31%-56%) with alloHSCT.

Regarding overall survival (OS)—a secondary end point—the 1-year rates were 94% (95% CI, 86%-97%) and 83% (95% CI, 73%-90%) in the Orca-T and alloHSCT arms, respectively (HR, 0.49; P = .11823).

“Deciding whether to pursue a transplant may be a bit easier now that we have more successful treatments for one of its biggest concerns: [GVHD],” Gwen Nichols, MD, chief medical officer at Blood Cancers United, formerly The Leukemia & Lymphoma Society, a resource representing all blood cancers by delivering support, resources, research, and services, said in an interview with Targeted Oncology.

“When patients go online to research transplant and weigh that decision with their doctor, they're going to read about [GVHD] — and it's scary. We can't always predict who will develop a severe case. But being able to tell patients that there are steps we can take to help reduce that risk should be reassuring for both the physician and the patient,” Nichols continued.

Details About the Trial

Orca-T is manufactured from highly purified cells derived from peripheral blood of related or unrelated matched donors.

The trial enrolled patients with acute leukemia in complete remission (CR) or CR with incomplete hematologic recovery; or with MDS that is indicated for alloHSCT per 2017 International Expert Panel recommendations and/or therapy-related/secondary MDS, with no more than 10% bone marrow blasts.³ Patients needed to be planning to undergo a matched related or unrelated donor alloHSCT with total body irradiation (TBI) and cyclophosphamide; TBI and etoposide; or busulfan, fludarabine, and thiotepa.

Key inclusion criteria comprised a resting cardiac ejection fraction of at least 45% or a shortening fraction of at least 27%; alanine aminotransferase and aspartate aminotransferase levels less than 3 times the upper level of normal (ULN); intermediate- or high-risk disease designation; and a total bilirubin level less than the ULN.

Investigators excluded patients who received a prior alloHSCT, those with a planned donor lymphocyte infusion, and those with planned pharmaceutical in vivo or ex vivo T-cell depletion.

Patients were randomly assigned to receive Orca-T plus single-agent tacrolimus or alloHSCT plus tacrolimus and methotrexate. In both arms, patients underwent myeloablative conditioning and used a matched related or unrelated donor.

Along with the primary end point of moderate-to-severe cGVHD-free survival at 1 year, secondary end points comprised time to moderate-to-severe cGVHD; OS; and the rate of patients free from both cGVHD and relapse at 1 year.

REFERENCES

1. FDA approves allogeneic regulatory T cell-based immunotherapy with HSPC and T cells-vldq for use in matched donor hematopoietic stem cell transplantation for adults with hematologic malignancies. News release. US FDA. June 30, 2026. Accessed June 30, 2026. https://tinyurl.com/2fj66cys

2. Meyer EH, Salhotra A, Gandhi AP, et al. Orca-T vs allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial. Blood. 2026;147(11):1168-1177. doi:10.1182/blood.2025031313

3. Precision-T: a randomized study of Orca-T in recipients undergoing allogeneic transplantation for hematologic malignancies (Orca-T). ClinicalTrials.gov. Updated September 26, 2025. Accessed October 6, 2025. https://clinicaltrials.gov/study/NCT05316701