Treatment with the allogeneic T-cell immunotherapy Orca-T led to an improvement in moderate-to-severe chronic graft-vs-host disease (cGVHD)–free survival compared with conventional allogeneic hematopoietic stem cell transplant (alloHSCT) in patients with advanced hematologic malignancies, meeting the primary end point of the phase 3 Precision-T trial (NCT05316701).1
Findings showed that at a median follow-up of 11.4 months (range, 0.2-24.3), patients treated with Orca-T (n = 93) experienced a 1-year cGVHD-free survival rate of 78% (95% CI, 65%-87%) compared with 38% (95% CI, 26%-51%) for those who underwent conventional alloHSCT (n = 94; HR, 0.26; _P_ < .00001).
Additionally, the 1-year overall survival (OS) rates were 94% (95% CI, 86%-97%) for the Orca-T arm vs 83% (95% CI, 73%-90%) for the alloHSCT arm (HR, 0.49; _P_ = .11823). The cumulative incidence of moderate-to-severe cGVHD was 13% (95% CI, 5%-23%) for Orca-T vs 44% (95% CI, 31%-56%) for alloHSCT (HR, 0.19; _P_ < .00002).
Full data from Precision-T will be presented at the [**51st Annual EBMT Meeting**](https://www.onclive.com/conference/ebmt-meeting) in April.
"Today, treating patients with serious blood cancers using alloHSCTs requires a difficult risk-benefit trade-off as clinicians aim to cure the disease while avoiding potentially deadly treatment-related toxicities, like GVHD," presenting study author Everett Meyer, MD, PhD, a hematologist and associate professor of medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Health Care, stated in a news release. "The Precision-T study showed double the rate of survival free from GVHD with Orca-T vs a conventional transplant, a relapse-free survival \[RFS\] rate of 76%, and no new safety concerns. These findings are highly encouraging and provide compelling new evidence as we work to solve for the critical factors contributing to the needs of this patient population."
The randomized, open-label, multicenter Precision-T trial enrolled patients 18 to 65 years of age with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), or acute mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi), with or without the presence of known minimal residual disease; or myelodysplastic syndromes (MDS) indicated for alloHSCT.2 Patients were required to be planning to undergo alloHSCT with a matched related or unrelated donor using a conditioning regimen of total body irradiation (TBI) plus cyclophosphamide; TBI plus etoposide; or busulfan, fludarabine, and thiotepa. Patients needed a disease risk index overall categorization of intermediate or high and a Karnofsky performance status of at least 70%.
Prior alloHSCT was not permitted, and patients could not receive corticosteroids or other immunosuppressive therapies.
Patients were randomly assigned to receive Orca-T or conventional alloHSCT. Patients in both groups received myeloablative conditioning.1
Along with the primary end point of cGVHD-free survival, secondary end points included time to moderate-to-severe cGVHD; 1-year RFS; 1-year GVHD-free survival; and OS.2
At baseline, the total trial population (n = 187) had a median age of 43.5 years (range, 19-65).1
Additional data showed that the 1-year RFS rate was 76% in the Ora-T arm vs 74% in the alloHSCT arm (HR, 0.80; _P_ = .49). The 1-year rate of non-relapse mortality was 3% for Orca-T compared with 13% for alloHSCT. Grade 3/4 acute GVHD occurred in 6% of patients in the Orca-T arm vs 17% of patients in the alloHSCT arm.
No new safety signals were reported. Grade 4 or higher infections were reported in 6% of patients in the Orca-T group vs 10% of patients in the alloHSCT group.
“Approximately 46,000 people are diagnosed with AML, ALL, and MDS in the United States each year, but only a fraction of them receive an alloHSCT within the current paradigm,” Rawan Faramand, MD, of the Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center, added in the news release. “Additional treatment options are needed, and the introduction of a cell therapy like Orca-T that leverages a precision-based approach could pave the way for a new standard of care for patients with various hematologic malignancies.”
### **References**
1. Orca Bio announces positive results from the pivotal phase 3 study of investigational Orca-T compared to allogeneic stem cell transplant for the treatment of hematologic malignancies. News release. Orca Bio. March 17, 2025. Accessed March 17, 2025. https://orcabio.com/orca-bio-announces-positive-results-from-the-pivotal-phase-3-study-of-investigational-orca-t-compared-to-allogeneic-stem-cell-transplant-for-the-treatment-of-hematologic-malignancies/
2. Precision-T: a randomized study of Orca-T in recipients undergoing allogeneic transplantation for hematologic malignancies (Orca-T). ClinicalTrials.gov. Updated March 17, 2025. Accessed March 17, 2025. https://clinicaltrials.gov/study/NCT05316701