On June 30, the U.S. Food and Drug Administration (FDA) approved allogeneic regulatory T-cell–based immunotherapy with hematopoietic stem and progenitor cell (HSPC) and T cells-vldq (Tregzi) 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 (GHVD)-free survival in the treatment of adults with hematologic malignancies.
Precision-T
Efficacy was evaluated in Precision-T (ClinicalTrials.gov identifier NCT05316701), a multicenter, open-label, randomized, controlled trial in adults with acute leukemias or myelodysplastic syndrome (MDS). In total, 187 patients were randomly assigned to receive either allogeneic regulatory T-cell–based immunotherapy with HSPC and T cells (n = 93)—referred to as Orca-T during the trial—followed by single-agent GVHD prophylaxis with tacrolimus, or unmanipulated allograft (n = 94) followed by GVHD prophylaxis with tacrolimus and methotrexate.
The primary efficacy outcome measure was chronic GVHD-free survival (cGFS), defined as the time from HSCT to death by any cause or moderate-to-severe chronic GVHD, as graded per National Institutes of Health consensus criteria and determined by a blinded, independent endpoint adjudication committee.
The median cGFS was not estimable (95% confidence interval [CI] = not estimable to not estimable) in the cell therapy arm vs 7.3 months (95% CI = 6.3–15.5 months) in the control arm (hazard ratio [HR] = 0.26, 95% CI = 0.14–0.47, P < .00001) after a median follow up of 8.48 months (range = 0–22 months) and 9.03 months (range = 0–20 months), respectively. The cumulative incidence of moderate-to-severe cGVHD estimate at 12 months was 12.6% (95% CI = 5.3%–23.1%) for the investigational arm and 44.0% (95% CI = 31.3%–56.1%) for the unmanipulated allograft control arm (HR = 0.19, 95% CI = 0.08–0.43, P = .00002). All 88 patients (100%) treated with the cell therapy regimen achieved a neutrophil count of 500/mm3 within 28 days of infusion. Of these, 53 patients (60.2%) had neutrophil counts above 500/mm3 on 3 consecutive days, confirming neutrophil recovery within 28 days of infusion.
The most common adverse reactions (incidence ≥ 20%) with the cell therapy regimen were mucositis, diarrhea, rash, viral infections, infections–pathogen unspecified, abdominal pain, vomiting, nausea, bacterial infections, hemorrhage, acute GVHD, edema, and fungal infections.
The prescribing information includes warnings and precautions for graft failure, GVHD, infusion reactions, secondary malignancies and malignancies of donor origin, and transmission of infectious agents.
Recommended Dosage
The newly approved therapy consists of three product components that are sequentially administered: HSPCs, regulatory T cells (Tregs), and conventional T cells (Tcons). The targeted doses for each component are as follows: HSPC: ≥ 1.0 × 106 viable cells/kg and Tregs: 1.3 × 106 to 3.5 × 106 viable cells/kg administered intravenously (IV) on day 0 followed by Tcons: 1.3 × 106 to 6.9 x 106 viable cells/kg administered IV on day +2 to day +3.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Priority Review. The therapy received Orphan Drug designation and Regenerative Medicine Advanced Therapy designation.
