Orca-T Tops Tacrolimus Methotrexate In Precision-T Phase 3 Trial

Key Takeaways

• Orca-T plus tacrolimus was associated with better survival free from moderate-to-severe chronic GVHD than conventional allograft with tacrolimus and methotrexate.
• Lower moderate-to-severe chronic GVHD, higher GVHD-free and relapse-free survival, and lower nonrelapse mortality were reported with Orca-T.
• Fewer serious infectious complications were reported with Orca-T, while one-year overall survival was numerically higher without a statistically significant difference.

In the Precision-T phase 3 trial, Orca-T plus tacrolimus improved survival free from moderate-to-severe chronic GVHD versus conventional allograft with tacrolimus and methotrexate, with a hazard ratio of 0.26. The randomized multicenter study enrolled adults with acute leukemias or myelodysplastic syndrome undergoing myeloablative allogeneic transplantation. One-year estimates and secondary outcomes also favored Orca-T across chronic GVHD, relapse-related composites, and non-relapse mortality. The comparison was between Orca-T plus tacrolimus and a conventional allograft using tacrolimus and methotrexate for GVHD prophylaxis after transplantation. The advantage was observed in adults receiving HLA-matched donor grafts in this myeloablative transplant population.

Precision-T was a randomized multicenter phase 3 trial that enrolled 187 adults with acute leukemias or myelodysplastic syndrome across transplant centers. All participants underwent myeloablative conditioning and received granulocyte colony-stimulating factor-mobilized peripheral blood grafts from HLA-matched donors. Patients were assigned to Orca-T with tacrolimus or to conventional allograft with tacrolimus and methotrexate. Orca-T was described as using purified donor regulatory T cells to prevent GVHD while requiring significantly less immunosuppression. The primary endpoint was survival free from moderate-to-severe chronic GVHD, and a stratified log-rank test showed the trial met that endpoint.

At 1 year, survival free from moderate-to-severe chronic GVHD was 78.0% with Orca-T and 38.4% with tacrolimus and methotrexate in the conventional arm. The cumulative incidence of moderate-to-severe chronic GVHD was 12.6% versus 44.0%, with a Gray test P value below .001. GVHD-free and relapse-free survival at 1 year was 63.1% in the Orca-T arm and 30.9% in the comparator arm, with P < .001. These one-year estimates for cGFS, chronic GVHD, and GRFS all favored Orca-T in the randomized cohorts. The arm-level results were consistent with the strong primary-endpoint effect estimate reported for the trial.

One-year non-relapse mortality was 3.4% with Orca-T and 13.2% with tacrolimus and methotrexate in the conventional arm, with P = .03. Serious infectious complications were also less frequent with Orca-T across the one-year safety findings. Overall survival at 1 year was 93.9% with Orca-T and 83.1% with tacrolimus and methotrexate, but that numerical difference was not statistically significant. The authors characterized Orca-T as a therapeutic option for GVHD prophylaxis with low toxicity. Together, the one-year findings paired lower nonrelapse mortality and fewer serious infections with higher GVHD-free and relapse-free survival in the randomized study.