Orca-T, an investigational allogeneic T-cell immunotherapy, is showing promise in the treatment of advanced hematologic malignancies. Preliminary findings from a phase 1 study and retrospective analyses of a phase 1b trial suggest that Orca-T offers a safe and effective alternative to conventional transplantation methods and post-transplant cyclophosphamide.
Phase 1 Study: Safety and Feasibility
Data from a phase 1 study (NCT05088356) presented at the 2025 Transplantation & Cellular Therapy Meetings, indicated that Orca-T, when combined with hematopoietic bone marrow stem cell transplantation using reduced-intensity conditioning (RIC), is a safe and feasible option for patients with advanced hematologic malignancies. The median follow-up was 10.4 months (range, 1-32).
Key findings from the interim analysis include:
- Median time for neutrophil engraftment: 15 days (range, 9-39)
- Median time for platelet engraftment: 19.5 days (range, 14-70)
- Median donor chimerism for CD15 at day 30: 100% (range, 99%-100%)
- Median donor chimerism for CD15 at day 90: 100% (range, 98%-100%)
- 12-month relapse-free survival (RFS) rate: 79% (95% CI, 65%-96%)
Safety data revealed moderate chronic graft-vs-host disease (GVHD) in 2 patients and grade 2 to 4 acute/late onset GVHD in 4 patients. Notably, no patients experienced grade 3 or 4 acute/late onset GVHD or severe chronic GVHD.
"We observed robust myeloid and T-cell engraftment; thus no dose escalation of conventional T cells was needed," noted Alejandro Villar-Prados, MD, PhD, a clinical fellow at Stanford University, in a poster presentation. "Orca-T in combination with RIC results in low incidences of acute and chronic GVHD, while maintaining a strong graft vs tumor effect."
Phase 1b Trial: Improved Overall Survival
Retrospective data from a phase 1b trial (NCT04013685) demonstrated improved overall survival (OS) with Orca-T compared to post-transplant cyclophosphamide in patients with high-risk hematologic malignancies. The findings were initially presented at the 2024 ASH Annual Meeting and reiterated at the 2025 Transplantation & Cellular Therapy Meetings.
The Orca-T treated patients (n = 77) achieved 1-, 2-, and 3-year OS rates of 96% (95% CI, 88%-99%), 88% (95% CI, 78%-94%), and 86% (95% CI, 73%-92%), respectively, compared to 82% (95% CI, 78%-87%), 73% (95% CI, 68%-79%), and 67% (95% CI, 61%-74%) in the post-transplant cyclophosphamide group (n = 293).
In the entire phase 1b cohort (n = 154), the 1-, 2-, and 3-year OS rates were 88% (95% CI, 83%-94%), 80% (95% CI, 74%-87%), and 76% (95% CI, 69%-84%), respectively, with a median follow-up of 30 months (range, 0-54).
Key Advantages of Orca-T
Orca-T is a precision-engineered cell therapy composed of defined stem and T cells. Unlike conventional transplants that use a heterogeneous mix of cells, Orca-T selects and separates these cells into distinct components, potentially reducing transplant-related mortality, especially in older patients.
According to Caspian Oliai, MD, MS, from Westwood Cancer Center, Orca-T achieves low non-relapse mortality and toxicities by using single-agent GVHD prophylaxis with tacrolimus, contrasting with the post-transplant cyclophosphamide approach that typically requires three immunosuppressants.
Ongoing Research
The phase 3 Precision-T trial (NCT05316701), which has completed enrollment, is further evaluating Orca-T versus standard allo-HCT in patients with advanced hematologic malignancies. This trial aims to provide more definitive data on the efficacy and safety of Orca-T in this patient population.
