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Myeloablative Orca-Q demonstrated efficacy and safety in high-risk hematologic malignancies.
Treatment with the precision-engineered allogeneic immunotherapy graft, Orca-Q with or without graft-vs-host disease (GVHD) prophylaxis displayed encouraging efficacy and safety, including low rates of GVHD and non-relapse mortality (NRM), in patients with advanced, high-risk hematologic malignancies, according to data from a phase 1 trial (NCT03802695) presented at the 2025 ASH Annual Meeting and Exposition.1
Findings demonstrated that no patients experienced primary graft failure; the median time to neutrophil engraftment was 11 days in patients who received GVHD prophylaxis (n = 18) and 15 days in those who were not administered GVHD prophylaxis (n = 26). There were no statistically significant differences in the rates of grade 3 or higher acute GVHD in patients who underwent GVHD prophylaxis vs those who did not (5.6% vs 8.4%), or in rates of moderate-to-severe chronic GVHD (11.8% vs 0%). Notably, 33% of patients administered GVHD prophylaxis experienced grade 2 or 3 infections compared with 17% of patients who did not receive GVHD prophylaxis (P = .12).
“We think this [Orca-Q] platform accelerates the immune reconstitution with low infection rates,“ lead study author Samer A. Srour, MB ChB, MS, said in a presentation of the data. “We are hoping to have a registrational phase 3 [study] sometime soon.”
Srour is an assistant professor in the Department of Stem Cell Transplantation of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.
Although allogeneic hematopoietic stem cell transplant represents the only potentially curative approach for patients with select hematologic malignancies, the approach is associated with impaired immune reconstitution and an increased risk of organ toxicity, infection, and disease relapse due to pharmacologic immunosuppression.
Orca-Q is an allogeneic immunotherapy graft intended to minimize GVHD while promoting graft-vs-leukemia and graft-vs-infection effects. The therapy comprises high-purity hematopoietic stem and progenitor cells, regulatory and invariant natural killer T cells, and T-cell subsets.
The ongoing multicenter, dose-expansion phase 1 study is enrolling patients 18 to 78 years of age with high-risk hematologic malignancies, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high- or very high–risk myelodysplastic syndrome (MDS), myelofibrosis, and chronic myeloid leukemia.1,2 Patients need to have a hematopoietic cell transplantation–specific comorbidity index (HCT-CI) of 4 or less, a Karnofsky performance status of at least 70, and adequate organ function.1
Enrolled patients with 8/8 HLA matched donors underwent myeloablative conditioning from days –10 to –2 prior to a fresh Orca-Q infusion on day 0. Notably, post-transplant cyclophosphamide and methotrexate were not permitted. Patients received either single-agent tacrolimus from day –1 to day 90 with tapering, or no GVHD prophylaxis.
The rate of primary graft failure through day 28 serves as the trial’s primary end point. Secondary end points include rates of acute and chronic GVHD; relapse-free survival (RFS); NRM; and GVHD and RFS (GRFS).
At baseline, the median age was 41 years (range, 27-55) in the GVHD prophylaxis arm vs 60 years (range, 20-70) in the non-prophylaxis arm, and the respective rates of female patients were 44% and 50%. Median follow-ups were 1531 days (range, 66-1825) and 234 days (range, 5-1418), respectively. Most patients in both arms were White (prophylaxis arm, 72.2%; non-prophylaxis arm, 96%) and not Hispanic or Latino (69%; 76%).
HCT-CI scores in the prophylaxis arm were 0 (50.0%), 1 (5.6%), 2 (22.2%), 3 (11.1%), and 4 (11.1%). These respective rates in the non-prophylaxis arm were 34.6%, 15.4%, 23.1%, 19.2%, and 7.7%. Primary disease types in the prophylaxis arm included AML (44.4%), ALL (33.3%), CML (16.6%), and MDS (5.5%). Patients in the non-prophylaxis group had AML (61.5%), ALL (11.5%), CML (11.5%), MDS (3.8%), and myelofibrosis (11.5%).
In the prophylaxis arm, 72.2% of patients were in first complete remission (CR), 22.2% were in second CR, and 5.6% had active disease. Among patients in the non-prophylaxis group, 61.5% were in first CR, 7.7% were in second CR, 7.7% were in third CR, and 23% had active disease. Seventy-eight percent of patients in the prophylaxis arm has matched-related donors vs 46% in the non-prophylaxis arm. The median ages of donors were 34 years (range, 23-52) and 47 years (range, 21-68), respectively. Most patients in the prophylaxis group underwent myeloablative conditioning with a total body irradiation–based approach (67%), whereas the majority of patients in the non-prophylaxis arm received a busulfan, fludarabine, and thiotepa–based regimen (88.5%).
Findings also showed that the 360-day NRM rates were 6% in the GVHD prophylaxis arm and 0% in the non-prophylaxis arm, with the difference not reaching statistical significance. Differences in RFS at 360 days were also not statistically significant, with rates of 88% in the prophylaxis group and 87% in the non-prophylaxis group.
The 360-day overall survival (OS) rates were 94% for the prophylaxis arm and 87% in the non-prophylaxis group. The 360-day GRFS rates were 77% and 79%, respectively. Differences in OS and GRFS were also not statistically significant between the 2 arms.
Notably, patients who did not receive GVHD prophylaxis had higher CD8-positive cell counts at day 28 vs the prophylaxis arm. However, no differences in T-cell, B-cell, and natural killer–cell reconstitution were reported after day 28.
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