Orca-T Immunotherapy Improves cGVHD-Free Survival in ALL, AML, MDS

Orca-T, an investigational allogeneic T-cell immunotherapy, improved chronic graft-vs-host disease (cGVHD)–free survival compared with allogeneic stem cell transplant (allo-HSCT) in patients with hematologic malignancies in the phase 3 Precision-T trial (NCT05316701), according to a press release from Orca Bio.¹

Allo-HSCT is a key piece in the paradigm for treating hematologic malignancies, but it comes with serious risks of complications, including GVHD.² In the Precision-T trial—which included patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS), and mixed-phenotype acute leukemia—Orca-T met the primary end point of statistically significant improvement in survival free of moderate to severe cGVHD compared with allo-HSCT.¹

The cohort of patients who received Orca-T showed a cGVHD-free survival rate of 78% at 1 year compared with 38% of patients who received standard allo-HSCT (HR, 0.26; P < .00001).

Orca-T is manufactured with highly purified regulatory T cells, hematopoietic stem cells, and conventional T cells from peripheral blood from matched donors. | Image credit: fotogurmespb - stock.adobe.com.jpg

“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,” Rawan Faramand, MD, Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, said in a statement.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.”

Overall survival (OS), a secondary end point, was 94% (95% CI, 86%-97%) at 1 year in the Orca-T arm and 83% (95% CI, 73%-90%) in the allo-HSCT arm (HR, 0.49; P = .11823). The cumulative incidence of moderate to severe cGVHD at 1 year was 13% (95% CI, 5%-23%) in the Orca-T cohort and 44% (95% CI, 31%-56%) in the allo-HSCT cohort (HR, 0.19; P < .00002).

"Today, treating patients with serious blood cancers using allogeneic stem cell transplants requires a difficult risk-benefit trade-off as clinicians aim to cure the disease while avoiding potentially deadly treatment-related toxicities, like GVHD," study author Everett Meyer, MD, PhD, hematologist and associate professor of medicine in blood and marrow transplantation and cellular therapy at Stanford Health Care, said. "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."

The Precision-T study randomized 187 patients to receive either Orca-T plus single-agent tacrolimus or allo-HSCT plus tacrolimus and methotrexate, with a median follow-up of 11.4 months (range, 0.2-24.3). In both arms, patients received myeloablative conditioning and used a related or unrelated matched donor. Additional exploratory end points at 1 year included the rate of relapse-free survival (76% vs 74% in the Orca-T and allo-HSCT groups, respectively), cumulative incidence of nonrelapse mortality (3% vs 13%, respectively), and cumulative incidence of grade 3 or 4 acute GVHD (6% vs 17%, respectively).

Grade 4 or higher infections occurred in 5% of patients in the Orca-T cohort and 10% of patients in the allo-HSCT cohort. No new safety concerns were identified in the study. The full results are to be presented at the 51st Annual Meeting of The EBMT in Florence, Italy.

“These exciting results underscore Orca Bio’s vision of transforming the treatment landscape for patients living with serious blood cancers, potentially standardizing curative treatment for diseases like AML, ALL, and MDS,” said Ivan Dimov, PhD, co-founder and CEO at Orca Bio. “We are working closely with the FDA and expect to submit a biologics license application this year. These results support the validity of our high-precision platform as we continue to advance our robust pipeline of allogeneic cell therapies for the treatment of hematologic malignancies, autoimmune diseases, and beyond.”

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://orcabio.com/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/

2. Typical treatment of acute myeloid leukemia (Except APL). American Cancer Society. Accessed March 19, 2025. https://www.cancer.org/cancer/types/acute-myeloid-leukemia/treating/typical-treatment-of-aml.html