Orca-T Yields Superior Survival Outcomes vs Allo-HSCT Across Subgroups in Advanced Hematologic Malignancies

Treatment with Orca-T prolonged moderate-to-severe chronic graft-vs-host disease (cGVHD)–free survival (cGFS) vs standard-of-care allogeneic hematopoietic stem cell transplant (allo-HSCT) in patients with advanced hematologic malignancies and varied demographic and clinical features—including older patients, those with high pre-transplant comorbidity, and those with high-risk disease—according to results from prespecified subgroup analyses of the phase 3 Precision-T trial (NCT05316701).¹

Results presented during the 2025 ASH Annual Meeting and Exposition showed that among the subgroup of patients older than 50 years of age, the 1-year cGFS rates were 74% with Orca-T (n = 31) and 35% with allo-HSCT (n = 32; HR, 0.30 (95% CI, 0.12-0.76; P = .007). The 1-year GVHD-free, relapse-free survival (GRFS) rates with these respective regimens were 59% and 23% (HR, 0.44, 95% CI, 0.21-0.91; P = .024). Furthermore, 94% of patients treated with Orca-T in this subgroup were alive at 1 year vs 80% of those who received allo-HSCT (HR, 0.48; 95% CI, 0.12-1.89; P = .28).

In patients with 3 or more pre-transplant comorbidities, the 1-year cGFS rates were 5.2% with Orca-T (n = 19) and 48% with allo-HSCT (n = 29; HR, 0.1; 95% CI, 0.01-0.76; P = .006). The 1-year GRFS rates with these respective regimens were 21% and 84% (HR, 0.37, 95% CI, 0.12-1.1; P = .062). One patient treated with Orca-T was alive at 1 year vs 6 of those who received allo-HSCT (HR, 0.26; 95% CI, 0.03-2.16; P = .176).

Among patients with high-risk disease, the 1-year cGFS rates were 24% with Orca-T (n = 25) and 46% with allo-HSCT (n = 24; HR; 0.39; 95% CI, 0.14-1.06; P = .057). The 1-year GRFS rates with these respective regimens were 36% and 63% (HR, 0.46, 95% CI, 0.2-1.05; P = .058). Notably, 1 OS event occurred in the Orca-T at 1 year vs 2 in the allo-HSCT arm (HR, 0.49; 95% CI, 0.04-5.44; P = .555).

“In subgroups of patients, cGFS, OS, and GRFS [rates] consistently favored Orca-T,” lead study author Everett Meyer, MD, PhD, and colleagues wrote in a poster presentation of the data. “These data suggest that the benefit of Orca-T extends to older patients and those with high-risk disease.”

Meyer is an associate professor of medicine (Blood and Marrow Transplantation and Cellular Therapy), of pediatrics (Stem Cell Transplantation), and, by courtesy, of surgery (Abdominal Transplantation) at Stanford University in California.

What prior data have been reported from Precision-T?

Orca-T is an investigational allogeneic T-cell immunotherapy that leverages purified donor regulatory T cells to prevent GVHD. Prior findings from Precision-T were presented during the 51st Annual EBMT Meeting. In the overall patient population, at a median follow-up of 11.4 months (range, 0.2-24.3), Orca-T (n = 93) significantly improved cGFS compared with SOC allo-HSCT with tacrolimus plus methotrexate prophylaxis (n = 94; HR, 0.26; 95% CI, 0.14-0.47; log-rank P < .00001).² The 1-year cGFS rates in these respective arms were 78.0% (95% CI, 65.0%-86.6%) and 38.4% (95% CI, 26.2%-50.5%).

Based on these prior findings from Precision-T, in October 2025, the FDA accepted and granted priority review to a biologics license application seeking the approval of Orca-T for the treatment of select patients with hematologic malignancies, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS).³

According to the study’s statistical analysis plan, the 56th cGFS event triggered the primary analysis, which occurred at a median follow-up of 9 months.¹ Subset analyses were subsequently conducted to further examine clinical outcomes with Orca-T according to several demographic and clinical variables.

What was the design of Precision-T?

The randomized, open-label, multicenter Precision-T trial enrolled patients with AML, ALL, mixed-phenotype acute leukemia, or MDS in complete remission (CR) or CR with incomplete hematologic recovery (CRi) who would have undergone standard allo-HSCT.² Patients were required to have a disease risk index score of intermediate or high and be 65 years of age or younger.¹

Eligible patients at 19 centers across the United States were randomly assigned to receive Orca-T (n = 88) or tacrolimus/methotrexate (Tac/MTX; n = 94). Patients in both groups received myeloablative conditioning or a total body irradiation–based regimen, and had an 8/8 HLA-matched donor.

The trial’s primary end point was cGFS.² Secondary end points included OS, GRFS, and the incidence of moderate-to-severe cGVHD.

In the current analysis, patient subgroups were identified according to differences in recipient age and sex, donor type, disease type, disease risk, and condition regimen received.¹ Both cGFS and GRFS were compared between treatment groups for each patient subset.

What were the baseline characteristics of patients in this study?

In the overall population, the median age for patients was 46 years (range, 33-55) in the Orca-T arm (n = 88) and 43 years (range, 32-55) in the allo-HSCT arm (n = 94). The majority of patients across both arms were male (Orca-T, 58%; allo-HSCT, 53%), had a Karnofsky score below 90 (78%; 72%), had 2 or fewer comorbidities (78%; 69%), and had intermediate-risk disease (72%; 74%). Most patients had AML (56%; 61%), followed by ALL (31%; 28%) and MDS (14%; 12%). Donor types were similar between matched related (49%; 51%) and matched unrelated (51%; 49%).

What additional efficacy data from Precision-T were reported at the 2025 ASH Annual Meeting?

In the intention-to-treat cohorts, the 1-year cGFS rate with Orca-T was 78% (95% CI, 65%-87%) vs 38% (95% CI, 26%, 51%) with Tac/MTX (HR, 0.26; 95% CI, 0.14-0.47: P < .00001). The GRFS rates with these respective regimens were 63% and 31% (HR, 0.37; 95% CI, 0.23-0.60; P < .00001). Furthermore, 94% of patients treated with Orca-T were alive at 1 year vs 83% of those who received Tac/MTX (HR, 0.49; 95% CI, 0.20-1.22; P = .12). Respective non-relapse mortality rates were 3.4% vs 14%. Of note, 1-year RFS rates were comparable between Orca-T and allo-HSCT groups at 76% vs 74%, respectively.

In the remaining subgroups, outcomes for cGFS favored Orca-T over Tac/MTX:

• Recipient age: HR, 0.24 (95% CI, 0.11-0.54) for patients 50 years of age or younger (P < .001)
• Recipient sex: HR, 0.24 (95% CI, 0.10-0.56) for men (P < .001); HR, 0.32 (95% CI, 0.14-0.77) for women (P = .007)
• Donor type: HR, 0.32 (95% CI, 0.14-0.77) for related donors (P = .007); HR, 0.21 (95% CI, 0.09-0.48) for unrelated donors (P < .001)
• Disease type: HR, 0.28 (95% CI, 0.06-1.41) for lymphoid disease (P = .100); HR, 0.26 (95% CI, 0.13-0.49) for myeloid disease (P < .001)
• Karnofsky performance status: HR, 0.33 (95% CI, 0.09-1.18) for scores less than 90 (P = .074); HR, 0.24 (95% CI, 0.12-0.47) for scores of at least 90 (P < .001)
• Disease risk: HR, 0.21 (95% CI, 0.10-0.44) for intermediate-risk disease (P < .001)
• Comorbidities: HR, 0.30 (95% CI, 0.15-0.57) for patients with no more than 2 comorbidities (P < .001)

OS and GRFS outcomes also consistently favored Orca-T across subgroups.

Disclosures: Meyer did not provide disclosures

References

1. Meyer EH, Salhotra A, Gandhi AP, et al. Orca-T improves chronic graph-versus-host disease free in patients with a broad range of demographic and clinical variables: Results of randomized, phase 3 trial. Blood. 2025;146(suppl 1):2477. doi:10.1182/blood-2025-2477
2. Meyer EH, Salhotra A, Gandhi AP, et al. Orca-T demonstrates improved survival free of chronic GvHD compared to conventional allogeneic hematopoietic stem cell transplant: a randomized phase 3 trial in advanced hematologic malignancies. Presented at: 51st Annual EBMT Meeting; March 30-April 2, 2025; Florence, Italy. Abstract OS15-01.
3. Orca Bio announces FDA acceptance and priority review of the biologics license application (BLA) for Orca-T to treat hematological malignancies. News release. Orca Bio. October 6, 2025. Accessed January 8, 2025. https://orcabio.com/orca-bio-announces-fda-acceptance-and-priority-review-of-the-biologics-license-application-bla-for-orca-t-to-treat-hematological-malignancies/