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 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 three 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 endpoint 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