Orca Bio Reports Promising Results for Orca-T Cell Therapy in Older Blood Cancer Patients at ASH 2025
核心洞察
Orca Bio (搜索) presented new clinical data at ASH 2025 showing Orca-T with reduced intensity conditioning achieved low rates of graft-versus-host disease and disease relapse in patients aged 60-75 with blood cancers.
A Phase 3 observational analysis demonstrated Orca-T delivered 94% overall survival compared to 81% with conventional PTCy-based therapy, with significantly lower non-relapse mortality rates.
Patient-reported outcomes from the Precision-T Phase 3 study showed Orca-T recipients experienced faster quality of life recovery, fewer ICU stays, and lower rehospitalization rates compared to conventional transplant.
Orca Bio (搜索) announced promising new clinical data for its investigational allogeneic T-cell immunotherapy Orca-T at the 67th American Society of Hematology (ASH) Annual Meeting, demonstrating the therapy's potential to expand treatment options for older patients with blood cancers who may not be eligible for standard intensive transplant regimens.
Reduced Intensity Conditioning Shows Promise in Older Patients
A single-center, open-label Phase 1 investigator-sponsored trial evaluated Orca-T in patients aged 60-75 (median 68 years) using a reduced intensity conditioning regimen (RIC) for treating acute myeloid leukemia (搜索) (AML), acute lymphoblastic leukemia (搜索) (ALL), myelodysplastic syndrome (搜索) (MDS) and myeloproliferative neoplasm (搜索) (MPN). The study demonstrated low incidence of both acute and chronic graft versus host disease (搜索) while maintaining low rates of disease relapse.
"Many older patients with hematological malignancies are not eligible for myeloablative allogeneic stem cell transplant due to the significant toxicities associated with it. A conventional reduced intensity alloHSCT can be safer and more tolerable, but it may also reduce the curative potential," said Everett Meyer, M.D., Ph.D., hematologist and associate professor of medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Health Care.
The trial enrolled 53 patients total, with 46 patients having 8/8 matched donors conditioned with fludarabine/melphalan/total body irradiation (TBI) or fludarabine/thiotepa/TBI. Notably, 23 patients were enrolled in a cohort eligible for outpatient treatment, marking the first time RIC Orca-T has been used in an outpatient setting.
All patients achieved successful neutrophil engraftment at a median of 15 days. At one year, there was no grade 3-4 acute graft-versus-host disease observed, and the rate of grade 2 acute GvHD was 12.3% (95% CI, 5-23%). The rate of moderate-to-severe chronic GvHD was 9.6% (95% CI, 3-21%). Relapse-free survival and graft versus host disease (搜索) relapse-free survival were 82% (95% CI, 72-94%) and 72% (95% CI, 60-87%), respectively. Overall survival reached 88% (95% CI, 79-98%) with non-relapse mortality of 10% (95% CI, 4-20%).
The outpatient-eligible cohort showed particularly encouraging results with 0% non-relapse mortality, 80% relapse-free survival (95% CI, 65-100%) and 95% overall survival (95% CI, 87-100%).
Phase 3 Analysis Shows Superior Outcomes Versus Standard Care
An observational analysis compared outcomes from 45 patients who received Orca-T in the Precision-T Phase 3 study to a historical cohort of 475 patients who received PTCy-based GvHD prophylaxis from the Center for International Blood and Marrow Transplant Research (CIBMTR).
At one year, overall survival was 94% with Orca-T compared to 81% with PTCy. Relapse-free survival was 86% and 70% for Orca-T and PTCy, respectively. Orca-T achieved 0% non-relapse mortality compared to 9.7% with PTCy, reaching statistical significance. Disease relapse occurred in 13.8% of the Orca-T cohort versus 21% in the PTCy cohort.
For patients over age 50, overall survival was 100% with Orca-T compared to 75% with PTCy. These outcomes were achieved using only single-agent tacrolimus for pharmacological GvHD prophylaxis with Orca-T recipients, in contrast to the triple-agent regimen used with PTCy.
Improved Quality of Life and Reduced Healthcare Utilization
Subset analyses from the Precision-T Phase 3 study comparing Orca-T to conventional allogeneic transplant plus tacrolimus and methotrexate (Tac/MTX) showed Orca-T demonstrated improved clinical outcomes across patient subgroups. For all patients, the rate of survival free from chronic GvHD was 78% with Orca-T versus 38% with Tac/MTX. For patients over age 50, chronic GvHD-free survival was 74% and 35% for Orca-T and Tac/MTX, respectively.
Patient-reported outcomes revealed marked improvements in health-related quality of life with Orca-T. FACT-BMT total scores were consistently higher for Orca-T recipients across all time points, with recipients exceeding baseline scores in physical well-being, functional well-being and transplant-specific subscales by day 100, while the conventional transplant arm did not surpass baseline until day 365.
Rehospitalizations due to adverse events occurred less frequently among Orca-T recipients (27.3% versus 45.7%), with fewer total hospitalization days per patient (30.6 vs. 40.8). Rehospitalization-free survival at 18 months was significantly improved with Orca-T, reaching 66.4% (95% CI: 54.0, 76.2) compared to 33.8% (95% CI: 18.5, 49.9) for conventional transplant (p=0.0096; HR 0.53 [0.32, 0.86]).
"We are energized by these new data, which reinforce our belief that Orca-T has the potential to expand curative treatment options to many more people living with serious blood cancers, including those who may not be eligible for a myeloablative transplant today, and even patients treated in the outpatient setting," said Nate Fernhoff, Ph.D., co-founder and chief executive officer at Orca Bio (搜索).
Regulatory Timeline and Next Steps
Orca-T is currently under Priority Review by the U.S. Food and Drug Administration with a Prescription Drug User Fee Act (PDUFA) target action date of April 6, 2026. The therapy has received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug Designation for the prevention of graft versus host disease (搜索) or death in patients eligible for hematopoietic stem cell transplant.
The company's Serene-T Phase 2 study evaluating Orca-T with reduced intensity conditioning recently opened for enrollment as the next step toward understanding the therapy's potential to provide treatment options for more patients in need.