Orca-T Displays cGVHD-Free Survival Benefit in Hematologic Malignancies

Overall survival outcomes were enhanced with Orca-T vs allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancies.

Orca-T, an allogeneic T-cell immunotherapy, met its primary end point of improved moderate-to-severe chronic graft-versus-host disease (cGVHD)-free survival vs standard of care (SOC) allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with hematologic malignancies, according to a press release from the drug’s developer, Orca Bio.¹

Results from the phase 3 Precision-T trial (NCT 05316701) showed that Orca-T exhibited a 1-year GVHD-free survival of 78% (95% CI, 65%-87%) vs 38% (95% CI, 26%-21%) in alloHSCT (HR, 0.26; P <.00001). Additionally, the estimated 1-year overall survival (OS) in the Orca-T group was 94% (95% CI, 86%-97%) vs 83% (95% CI, 73%-90%) with alloHSCT (HR, 0.49; P = .11823). Furthermore, the cumulative incidence of moderate-to-severe cGVHD was 13% (95% CI, 5%-23%) and 44% (95% CI, 31%-56%), respectively (HR, 0.19; P <.00002).

“Today, treating patients with serious blood cancers using allogeneic [SCTs] requires a difficult risk-benefit trade-off as clinicians aim to cure the disease while avoiding potentially deadly treatment-related toxicities, like GVHD," presenting author Everett Meyer, MD, PhD, hematologist and associate professor of Medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Health Care, said in the news release.¹ "The Precision-T study showed double the [GVHD-free survival rate] with Orca-T vs a conventional transplant, a relapse-free survival [RFS] rate of 76%, and no new safety concerns. These findings are highly encouraging and provide compelling new evidence as we work to solve the critical factors contributing to the needs of this patient population."

Patients with acute myeloid, lymphoid, or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery and those with myelodysplastic syndromes (MDS) and/or therapy-related or secondary MDS with 10% or less blast burden in the bone marrow were enrolled on trial.² Patients were randomly assigned 1:1 to receive either Orca-T or alloHSCT.

Patients in the Orca-T arm initially received a myeloablative conditioning regimen followed by Orca-T. Afterward, a single-agent GVHD prophylaxis with tacrolimus was given at least 3 days following Orca-T dosing. Those in the SOC arm received an unmanipulated allograft derived from the peripheral of a matched donor administered after a myeloablative conditioning regimen. A dual-agent prophylaxis comprising tacrolimus plus methotrexate was given beginning day -3.

The patient population on study (n = 187) had a median age of 43.5 years (range, 19-65). The median follow-up time was 11.4 months (range, 0.2-23.4). The primary end point of the study was cGVHD-free survival. Secondary end points included time to moderate or severe GVHD, 1-year RFS, and OS.

Additional efficacy data revealed that the 1-year RFS rates in the Orca-T and alloHSCT arms were 76% and 74%, respectively (HR, 0.80; P = .49). Furthermore, the cumulative non-relapse mortality incidence was 3% vs 13% in each respective arm, with cumulative GVHD grade 3 or 4 incidences of 6% and 17%.

No new safety signals were identified with Orca-T and infections of grade 4 severity or higher per Common Terminology Criteria for Adverse Events (CTCAE) were observed in 6% of patients in the Orca-T arm and 10% of those in the alloHSCT arm.

“Approximately 46,000 people are diagnosed with acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], and MDS in the US each year, but only a fraction of them receive an allogeneic [SCT] within the current paradigm,” Rawan Faramand, MD, assistant member of Blood and Marrow Transplant and Cellular Immunotherapy at the Moffitt Cancer Center, said in the news release.¹ “Additional treatment options are needed, and the introduction of a cell therapy like Orca-T that leverages a precision-based approach could pave the way for a new standard of care for patients with various hematologic malignancies.”

The complete results will be presented at the upcoming 51st Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) in April 2025.

References

1. Orca Bio announces positive results from the pivotal phase 3 study of investigational Orca-T® compared to allogeneic stem cell transplant for the treatment of hematologic malignancies. News release. Orca Bio. March 17, 2025. Accessed March 17, 2025. https://tinyurl.com/26edwyup
2. Precision-T: a randomized study of Orca-T in recipients undergoing allogeneic transplantation for hematologic malignancies (Orca-T). ClinicalTrials.gov. Updated March 17, 2025. Accessed March 17, 2025. https://tinyurl.com/y9ubftdy