Orca-T Improves cGVHD-Free Survival Across Hematologic Malignancies

Red blood cells flowing realistically, 3D rendering: © Kodjovi - stock.adobe.com

A statistically significant improvement in survival free of moderate-to-severe chronic graft-vs-host disease (cGVHD) was seen with Orca-T vs treatment with conventional allogeneic stem cell transplant (alloHSCT) at 1 year in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS), and mixed-phenotype acute leukemia (MPAL), meeting the primary end point of the pivotal phase 3 Precision-T study (NCT05316701).¹

The study included patients (n = 187) with a median age of 43.5 years (range, 19-65) who were randomly assigned in a 1:1 fashion to receive Orca-T plus single-agent tacrolimus (TAC) or alloHSCT plus TAC methotrexate.² At a median follow-up of 11.4 months (range, 0.2-24.3) across both arms, the primary end point of survival free of cGVHD was 78% (95% CI, 65%-87%) in the Orca-T arm (n = 93) vs 38% (95% CI, 26%-51%) in the alloHSCT arm (n = 94; HR, 0.26; P <.00001).

At the interim analysis, the secondary end point of overall survival (OS) was 94% (95% CI, 86%-97%) in the Orca-T arm and 83% (95% CI, 73%-90%) in the alloHSCT arm (HR, 0.49; P =.11823). For cumulative incidence of moderate-to-severe cGVHD, another secondary end point of the study, the rate was 13% in the Orca-T arm (95% CI, 5%-23%) and 44% (95% CI, 31%-56%) in the alloHSCT arm, respectively (HR, 0.19; P <.00002).

“The Precision-T study showed double the rate of survival free from GVHD with Orca-T vs a conventional transplant, a relapse-free survival rate of 76% and no new safety concerns. These findings are highly encouraging and provide compelling new evidence as we work to solve for the critical factors contributing to the needs of this patient population,” said presenting author Everett Meyer, MD, PhD, hematologist and associate professor of medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Health Care, in a press release.

Precision-T, a randomized, open-label, multicenter study, evaluated the safety, efficacy and tolerability of Orca-T, an investigational allogeneic T-cell immunotherapy, vs conventional alloHSCT across multiple hematologic malignancies.² Across both groups, patients received myeloablative conditioning and used a related or unrelated matched donor.

“Orca-T is a high precision immunotherapy that is a more organized fashion to create immune reconstitution. Based on the new changes in post-transplant cyclophosphamide, we wanted to compare Orca-T [with] posttransplant cyclophosphamide since we currently are doing a study with Orca-T against the standard of care,” Alexandra Gomez Arteaga, MD, hematologist/oncologist in the bone marrow transplant and cellular therapy program at Weill Cornell Medicine in New York, New York, told Targeted Oncology^TM, in an interview.

Orca-T previously was granted regenerative medicine advanced therapy and orphan drug designations from the FDA for the prevention of GVHD or death in patients eligible for hematopoietic stem cell transplant.¹

Additional findings from the study showed that for exploratory end points at 1 year, the rate of relapse-free survival was 76% vs 74% in the Orca-T and alloHSCT arms, respectively (HR, 0.80; P = .49). In the Orca-T and alloHSCT arms, the cumulative incidence of non-relapse mortality was 3% and 13%, respectively, and the cumulative incidence of grade 3 or 4 acute GVHD was 6% and 17%, respectively.

There were also no new safety issues seen with Orca-T. Infections deemed grade 4 or greater per CTCAE scoring were observed in 6% and 10% of patients in the Orca-T and alloHSCT arms, respectively.

Complete findings from the study will be presented on April 2, 2025, at the 51st Annual Meeting of the EBMT in Florence, Italy.

“Approximately 46,000 people are diagnosed with AML, ALL and MDS in the US each year, but only a fraction of them receive an allogeneic stem cell transplant within the current paradigm,” said Rawan Faramand, MD, Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, in the press release. “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.”

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/yf2mr3kk

2. Precision-T: A randomized study of Orca-T in recipients undergoing allogeneic transplantation for hematologic malignancies (Orca-T). ClinicalTrials.gov. Accessed Updated March 17, 2025. March 17, 2025. https://clinicaltrials.gov/study/NCT05316701