FDA Approves Orca-T for Matched Donor HSCT in Hematologic Malignancies

The FDA has approved allogeneic regulatory T cell–based immunotherapy with hematopoietic stem and progenitor cell (HSPC) and T cells-vldq (Tregzi; Orca-T) for use in matched donor hematopoietic stem cell transplantation (HSCT) with a myeloablative preparative regimen, for hematopoietic and immunologic reconstitution, and to improve chronic graft-vs-host disease (cGHVD)–free survival in the treatment of adults with hematological malignancies.

The regulatory decision was supported by data from the phase 3 Precision-T trial (NCT05316701), in which adult patients with acute leukemias or myelodysplastic syndromes (MDS) who received Orca-T (n = 93) achieved a median cGFS that was not estimable (NE; 95% CI, NE-NE) vs 7.3 months (95% CI, 6.3-15.5) months in patients in the control arm treated with unmanipulated allograft followed by GVHD prophylaxis with tacrolimus and methotrexate (n = 94; HR, 0.26; 95% CI, 0.14-0.47; P < .00001). The median follow-ups were 8.48 months (range, 0-22) and 9.03 months (range, 0-20), respectively.

How was the Precision-T trial designed?

Precision-T was a multicenter, open-label, randomized, controlled trial that enrolled 187 adult patients with acute leukemias or MDS undergoing matched donor HSCT with a myeloablative preparative regimen.^1,2

Patients were randomly assigned to receive an Orca-T (n = 93) followed by single-agent GVHD prophylaxis with tacrolimus, or an unmanipulated allograft (n = 94) followed by GVHD prophylaxis with tacrolimus plus methotrexate.¹

Orca-T consists of 3 components: HSPCs, regulatory T cells (Tregs), and conventional T cells (Tcons). These components are manufactured from the donor graft and administered sequentially. The targeted doses were at least 1.0 × 10⁶ viable HSPCs/kg and 1.3 × 10⁶ to 3.5 × 10⁶ viable Tregs/kg, both given intravenously on day 0, followed by 1.3 × 10⁶ to 6.9 × 10⁶ viable Tcons/kg given intravenously on day 2 or day 3.

The primary end point was cGFS, defined as time from HSCT to death from any cause or moderate to severe cGVHD per National Institutes of Health consensus criteria, as determined by a blinded, independent end point adjudication committee.

What additional efficacy and safety data supported the approval?

The 12-month cumulative incidence of moderate to severe cGVHD was 12.6% (95% CI, 5.3%-23.1%) in the Orca-T arm vs 44.0% (95% CI, 31.3%-56.1%) in the unmanipulated allograft control arm (HR, 0.19; 95% CI, 0.08-0.43; P = .00002).

All patients treated with Orca-T achieved an absolute neutrophil count of at least 500/mm³ within 28 days of infusion; of these patients, 60.2% had neutrophil counts above that threshold on 3 consecutive days, confirming durable neutrophil recovery.

The most common adverse reactions reported in at least 20% of patients treated with Orca-T were mucositis, diarrhea, rash, viral infections, infections of unspecified pathogen, abdominal pain, vomiting, nausea, bacterial infections, hemorrhage, acute GVHD, edema, and fungal infections.

The prescribing information for Orca-T carries warnings and precautions for graft failure, GVHD, infusion reactions, secondary malignancies and malignancies of donor origin, and transmission of infectious agents.¹

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. FDA. June 30, 2026. Accessed June 30, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-allogeneic-regulatory-t-cell-based-immunotherapy-hspc-and-t-cells-vldq-use-matched
2. A study comparing Orca-T to standard of care in patients undergoing allogeneic hematopoietic stem cell transplant for hematologic malignancies (Precision-T). ClinicalTrials.gov. Updated March 4, 2026. Accessed June 30, 2026. https://clinicaltrials.gov/study/NCT05316701