Treatment with Orca-Q led to high engraftment rates and promising survival outcomes in patients with high-risk hematologic malignancies with haploidentical donors, according to data from a phase 1 trial (NCT03802695) presented at the 2026 Transplantation & Cellular Therapy (TCT) Meetings.1
Findings showed that Orca-Q was successfully manufactured and administered to all patients (n = 39), with a vein-to-vein time of less than 72 hours for all patients. All patients achieved neutrophil engraftment by day 19 following initial infusion, and engraftment was reached at a median of 11 days. Notably, 2 patients who received busulfan-based conditioning experienced secondary graft failure.
Orca-Q in High-Risk Hematologic Malignancies With Haploidentical Donors: Phase 1 Data
- Treatment with Orca-Q yielded high engraftment rates and promising survival outcomes in patients with high-risk hematologic malignancies with haploidentical donors.
- All patients experienced successful manufacturing and administration of Orca-Q with a vein-to-vein time of less than 72 hours for all patients, and all patients achieved neutrophil engraftment by day 19.
- The 1-, 2-, and 3-year OS rates were 80%, 77%, and 77%, respectively; the 1-year RFS and GRFS rates were 77% and 72%, respectively.
At a median follow-up of 937 days (range, 19-1825), the 1-, 2-, and 3-year overall survival (OS) rates were 80%, 77%, and 77%, respectively. The 1-year relapse-free survival (RFS) rate was 77%, and the 1-year graft-vs-host disease (GVHD) RFS (GFRS) rate was 72%. At 1 year, the non-relapse mortality (NRM) rate was 5.8%, and the relapse incidence at 1 year was 18.2%.
Additionally, grade 3/4 acute GVHD occurred in 8.1% of patients through day 180; however, no patients experienced moderate-to-severe chronic GVHD within the first year of treatment. Grade 3 or higher infections per Blood and Marrow Transplant Clinical Trials Network (BMT CTN) criteria were reported in 5.3% of patients through the first year.
“These findings support the safety and efficacy of Orca-Q in reducing GVHD and achieving durable remissions,” lead study author Amandeep Salhotra, MD, and colleagues wrote in a poster presentation of the data. “The phase 1 study continues to enroll patients to confirm these results.”
Salhotra is an associate professor in the Division of Leukemia of the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California.
What was the rationale for investigating Orca-Q in patients with high-risk hematologic malignancies?
Although patients with hematologic malignancies without matched donors could undergo haploidentical hematopoietic stem cell transplant (haplo-HSCT), this method remains limited by immunological barriers, leading to risks of GVHD, delayed immune recovery, and variable relapse rates.
Thusly, investigators sought to evaluate the precision-engineered, cellular immunotherapy Orca-Q in patients with different donor types undergoing HSCT after myeloablative conditioning or non-myeloablative/reduced intensity conditioning.
The dose-expansion portion of the study is enrolling patients with high-risk hematologic malignancies, including acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndromes, who are eligible for myeloablative conditioning and haplo-HSCT. Forty-four patients were enrolled in total, and data were presented for 39 patients under 65 years of age.
Other key inclusion criteria comprise a matched 8/8 or 7/8 HLA related or unrelated donor, or a related haploidentical donor.2 Patients with also need to be in complete remission or have no more than 10% bone marrow blast cells.
Patients who underwent prior allogeneic stem cell transplant are excluded.
All patients are receiving myeloablative conditioning and either busulfan, fludarabine, and thiotepa; total-body irradiation (TBI), fludarabine, and thiotepa (TFT); or TBI and fludarabine.1
Investigators are following patients for 1 year to measure rates of GVHD and relapse, and longer follow-up is looking at OS. GRFS is defined as the time from transplant to first occurrence of grade 3/4 acute GVHD or moderate-to-severe chronic GVHD.
Dose-limiting toxicities and the rate of graft failure reported by 28 are serving as the trial’s primary end points.2 Secondary end points include neutrophil engraftment through day 28, platelet engraftment through day 50, secondary graft failure through day 100, chronic GVHD through day 365, NRM through day 365, relapse rate through day 365, GFRS through day 365, disease-free survival through day 365, and OS through day 365.
In the 39 patients presented in the TCT dataset, the median age was 44 years (range, 21-64), and 77% of patients were male.1
What data were reported for patients treated with a TFT regimen?
“Outcomes appeared favorable in the TFT subgroup, with improved survival, GRFS, and lower relapse incidence compared [with] other regimens,” Salhotra and study authors noted.
At a median follow-up of 1244 days, patients treated with a TFT regimen (n = 14) achieved 1-, 2-, and 3-year OS rates that were all 85%. The 1-year RFS and GRFS rates were also both 85%, and the 1-year NRM rate was 7.7%. Furthermore, the 1-year relapse incidence was 8.4%.
No patients in this subgroup experienced grade 3/4 acute GVHD through day 180 or moderate-to-severe chronic GVHD through day 365. Grade 3 or higher infections per BMT CTN criteria were reported in 7.1% of patients.
References
- Salhotra A, Srour S, Abedi M, et al. Preliminary safety and efficacy of myeloablative Orca-Q in patients with haploidentical donors. Presented at: 2026 Transplantation & Cellular Therapy Meetings; February 4-7, 2026; Salt Lake City, UT. Abstract 345.
- A phase 1 study of Orca-Q in recipients undergoing allogeneic transplantation for hematologic malignancies. ClinicalTrials.gov. Updated December 4, 2025. Accessed February 11, 2026. https://clinicaltrials.gov/study/NCT03802695
