Orca-Q Shows Promise in High-Risk Hematologic Cancers and BFT Conditioning May Synergize With the Agent

The precision-engineered allogeneic T-cell immunotherapy Orca-Q demonstrated rapid immune reconstitution with a low risk of infection in patients with high-risk hematologic malignancies who underwent myeloablative conditioning for allogeneic hematopoietic stem cell transplantation (HSCT) with HLA-identified donors in an ongoing phase 1 study (NCT03802695).1 Preliminary data presented at the 2025 Transplant and Cellular Therapy Meetings also showed that busulfan/fludarabine/thiotepa (BFT) conditioning may synergize with Orca-Q for improved disease control.

“Administration of Orca-Q without post-transplant pharmacological graft-vs-host disease [GVHD] prophylaxis showed promising clinical outcomes at 1-year follow-up. Orca-Q offers similar benefits as T-cell depletion, without the compromises typically observed,” Amandeep Salhotra, MD, lead study author and a hematologist-oncologist and associate professor in the Division of Leukemia at City of Hope in Duarte, California, wrote in a poster presentation of the data. “Orca-Q….seeks to maintain graft vs leukemia/infection effects while minimizing GVHD without the need for pharmacological suppression.”

The 1-year overall survival (OS) rate was 85% (95% CI, 52%-98%) among patients who received Orca-Q (n = 14) in the phase 1 trial. Additionally, patients experienced a 1-year relapse-free survival (RFS) rate of 85% and GVHD-free RFS (GRFS) rate of 77%. The neutrophil and platelet engraftment rate was 100% with a median time of 11 days (range, 10-19).

Further data showed that of the 11 patients who received Orca-Q and BFT without GVHD prophylaxis, 2 developed acute GVHD, none had chronic GVHD, and 1 died of disease relapse at 1 year. Among this group of patients, the 1-year OS, RFS, and GRFS rates were all 90%. Notably, BFT conditioning has shown promising disease control with Orca-T, according to Salhotra.

Enrollment into the Orca-Q Study and Baseline Characteristics

The phase 1 study of Orca-Q is currently ongoing, with Orca-Q that was centrally manufactured by Orca Bio from G-CSF mobilized peripheral blood and administered without GVHD prophylaxis. Patients with acute leukemia, high- or very high-risk myelodysplastic syndrome, or myelofibrosis are included in the study and patients must have adequate organ function and must be 18 to 65 years old at enrollment.1,2 Patients underwent myeloablative conditioning for allogeneic HSCT with HLA-identical donors (8/8 match, 50% related) on day –10 to –2 and were not permitted to receive post-transplant cyclophosphamide or other immunosuppressive therapies post-infusion.

Additional eligibility criteria noted that the estimated glomerular filtration rate must be greater than 50 mL/minute, the cardiac ejection fraction at rest must be at least 45% or the shortening fraction must be at least 27% by echocardiogram or radionuclide scan, and the diffusing capacity of the lung for carbon monoxide must be at least 50% when adjusted for hemoglobin.2 Furthermore, patients must have total bilirubin levels less than 1.5 times the upper limit of normal and alanine transaminase as well as aspartate transaminase levels less than 3 times the upper limit of normal.

The primary end points of the study are dose-limiting toxicities and primary graft failure through day 28 in the dose expansion phase. Additional outcomes measured include time to engraftment, GVHD incidence, infection rate, non-relapse mortality (NRM), GRFS, OS, and RFS.1

Among the 14 patients enrolled in arm C of this study that had been treated as of July 2024, the median age was 41 years (range, 25-66) and 42.9% of patients were female. Patients had acute lymphoblastic leukemia (14.3%), adult acute myeloid leukemia (50.0%), chronic myeloid leukemia (14.3%), and myelofibrosis (21.4%), and most were White (13/14). Conditioning regimens included BFT/TS BFT (78.6%) or total body irradiation-based (21.4%) and disease risk was most commonly intermediate (78.6%). Remission status was most frequently CR1 (57.1%), and HCT-CI scores were 0 (50.0%), 1 (14.3%), 2 (21.4%), and 3 (14.3%).

Additional Findings

All recipients of Orca-Q received the agent with a vein-to-vein time of less than 72 hours.

“One patient who received total body irradiation experienced grade 3 acute GVHD and subsequently developed secondary graph loss, but no disease relapse. Two patients had grade 2 acute GVHD, and only 1 case of mild chronic GVHD was observed. Two cases of grade 2 and 1 case of grade 3 infection were detected. Within the first year, 2 patients relapsed and died while no NRM was recorded.”

The study authors concluded that Orca-Q with no GVHD prophylaxis demonstrated low rates of GVHD and NRM. The phase 1 study continues to enroll patients.

Disclosures: Salhotra received research funding from Orca Biosystems, Rigel, BMS, Speakers Bureau, and Sanofi.

References

1. Salhotra A, Abedi M, Srour SA, et al. Preliminary safety and efficacy of myeloablative Orca-Q with no GvHD prophylaxis for treatment of advanced hematologic malignancies. Presented at: 2025 Transplant and Cellular Therapy Meetings; February 12-15, 2025; Honolulu, HI. Abstract 136.
2. A phase 1 study of Orca-Q in recipients undergoing allogeneic transplantation for hematologic malignancies. ClinicalTrials.gov. Updated April 3, 2024. Accessed February 14, 2025. https://clinicaltrials.gov/study/NCT03802695