Orca-T, a T-cell immunotherapy, significantly improved survival free of moderate-to-severe chronic graft-versus-host disease (cGvHD) compared with allogeneic hematopoietic stem cell transplant (alloHSCT) in the phase 3 Precision-T study for patients with acute myeloid leukemia, acute lymphoblastic leukemia, high-risk myelodysplastic syndrome and mixed-phenotype acute leukemia, according to a news release from the drug’s manufacturer, Orca Bio.
After a median follow-up time of 11.4 months, the primary end point of survival free of cGvHD was 78% in those who received Orca-T (93 patients) and 38% in those who received alloHSCT (94 patients). An interim analysis of the secondary end point of overall survival showed rates of 94% with Orca-T arm and 83% with alloHSCT. An additional secondary end point, the cumulative incidence of moderate-to-severe cGvHD, was 13% with Orca-T arm versus 44% with alloHSCT.
Glossary:
Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT): a procedure where a patient receives stem cells from a donor to replace their bone marrow.
Graft-versus-Host Disease (GvHD): a condition that can occur after a stem cell or bone marrow transplant when the transplanted cells attack the recipient’s body tissues.
Moderate-to-Severe Chronic GvHD (cGvHD): a prolonged form of GvHD that can cause long-term symptoms, such as skin rashes, liver problems and digestive issues.
Non-Relapse Mortality: death occurring in patients due to causes other than the return of the original cancer, such as infection or organ failure, after a transplant.
Overall Survival: the length of time from the start of treatment until death from any cause.
At one year, exploratory endpoints showed a relapse-free survival rate of 76% in the Orca-T arm and 74% in the alloHSCT arm. The cumulative incidence of non-relapse mortality was 3% in the Orca-T arm and 13% in the alloHSCT arm. Additionally, the cumulative incidence of grade 3 (severe) or 4 (life-threatening) acute GvHD was 6% in the Orca-T arm and 17% in the alloHSCT arm.
No new safety concerns were identified with Orca-T. Grade 4 or higher infections occurred in 6% of patients in the Orca-T arm and 10% in the alloHSCT arm.
"The Precision-T study showed double the rate of survival free from GvHD with Orca-T versus a conventional transplant, a relapse-free survival rate of 76% and no new safety concerns,” Dr. Everett Meyer said in the release. “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."
Meyer, the presenting author of this study, is a hematologist and associate professor of medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Health Care.
The complete results will be presented April 2, 2025, at the 51st Annual Meeting of the European Society for Blood and Marrow Transplants (EBMT) in Florence, Italy.
More on Orca-T and The Precision-T Trial
Orca-T, an investigational allogeneic T-cell immunotherapy, consists of highly purified regulatory T-cells, CD34+ stem cells and conventional T-cells from peripheral blood of related or unrelated matched donors. The U.S. Food and Drug Administration (FDA) has granted Orca-T regenerative medicine advanced therapy and orphan drug designation for preventing GVHD or death in patients eligible for hematopoietic stem cell transplant.
According to an article from the Cleveland Clinic, GvHD is a complication that may arise following treatment with alloHSCT, where you receive blood-forming stem cells from a donor. This transplant is often used to treat blood cancers like leukemia or lymphoma and bone marrow diseases like aplastic anemia. In GvHD, the donor’s cells see your body’s cells as a threat and attack them, leading to complications.
Regenerative medicine advanced therapy designation is granted to a drug that is a regenerative medicine therapy, such as cell therapy, tissue engineering product, or human cell and tissue product, intended to treat or cure a serious disease, according to the official FDA website, fda.gov. Furthermore, according to the regulatory website, orphan drug designation is a status granted by the U.S. FDA to drugs and biologics intended to treat rare diseases or conditions.
Precision-T is a randomized, open-label, multi-center study evaluating the safety, efficacy, and tolerability of Orca Bio’s investigational allogeneic T-cell immunotherapy, Orca-T, compared to conventional alloHSCT. The study received guidance from the U.S. FDA and involved patients with acute myeloid leukemia, acute lymphoblastic leukemia, high-risk myelodysplastic syndrome and mixed-phenotype acute leukemia. Nineteen leading treatment centers across the U.S. enrolled 187 patients in the trial.
“Approximately 46,000 people are diagnosed with [acute myeloid leukemia, acute lymphoblastic leukemia and high-risk myelodysplastic syndrome] in the U.S. each year, but only a fraction of them receive an allogeneic stem cell transplant within the current paradigm,” Dr. Rawan Faramand, Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, said in the news 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.”
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