Orca-T outperforms standard stem cell transplant for blood cell cancer
Precision-T study tested treatment on 187 people with different leukemias
Orca-T, Orca Bio‘s investigational allogeneic stem cell transplant for treating blood cell cancers, more than doubled the rate of survival free from moderate to severe graft-versus-host disease, or GvHD, when donated cells attack a patient’s healthy cells, over conventional allogeneic stem cell therapy.
That’s according to data from the Phase 3 Precision-T (NCT05316701) clinical trial that also showed the candidate therapy extended overall survival and relapse-free survival, the time alive without a relapse, after a year beyond conventional transplants. Orca Bio plans to submit the findings to the U.S. Food and Drug Administration (FDA) this year to support an application toward the therapy’s approval, the company stated in a press release.
Trial data will also be presented next month in Italy at the 51st annual meeting of the European Society for Blood and Marrow Transplantation by Everett Meyer, MD, PhD, a hematologist and associate professor of medicine in blood and marrow transplantation and cellular therapy at Stanford Health Care in California.
“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,” Meyer said. “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.”
In acute leukemias, genetic defects in hematopoietic stem cells, or those that give rise to all types of blood cells, lead to abnormal blood cells that rapidly grow out of control. Acute leukemia types include acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and mixed-phenotype acute leukemia (MPAL). Myelodysplastic syndrome (MDS) is another type of blood cancer that can develop into AML.
A hematopoietic stem cell transplant is an option for leukemias that involves replacing defective hematopoietic stem cells, which are killed off with chemotherapy, with healthy stem cells. This lets the stem cells repopulate the blood with healthy, noncancerous cells.
Such transplants can either be autologous, when stem cells are harvested from a patient’s own body, or allogeneic, meaning cells are sourced from donors. GvHD is a serious side effect of allogeneic stem cell transplants because immune cells from the donor can see the recipient’s body as foreign and launch an attack, which can disrupt organ function and cause permanent damage.
“Treating patients with serious blood cancers using allogeneic stem cell transplants requires a difficult risk-benefit tradeoff as clinicians aim to cure the disease while avoiding potentially deadly treatment-related toxicities, like GvHD,” Meyer said.
Comparing Orca-T, conventional allogeneic stem cell therapy
Orca-T is an investigational allogeneic stem cell therapy being evaluated for multiple types of blood cancers. It’s composed of healthy hematopoietic stem cells, highly purified regulatory T-cells, a type of anti-inflammatory immune cell, and other T-cells derived from the blood of related or unrelated matched donors.
The FDA granted Orca-T regenerative medicine advanced therapy and orphan drug status to prevent GvHD or death in patients eligible for hematopoietic stem cell transplant. These designations are intended to help speed the development of new therapies for rare diseases.
“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 [blood cancers],” said Rawan Faramand, MD, a blood and marrow transplant and cellular immunotherapy specialist at the Moffitt Cancer Center in Florida.
Precision-T is an ongoing open-label Phase 3 study designed to evaluate the safety, tolerability, and efficacy of Orca-T compared with a conventional allogeneic hematopoietic stem cell transplant (alloHSCT).
In total, 187 people with ALL, AML, MPAL, or MDS, ages 19-65, were randomly assigned to Orca-T plus tacrolimus (an immunosuppressant medication used to prevent organ rejection) or alloHSCT plus tacrolimus and methotrexate (a chemotherapy drug and immunosuppressant). Both groups underwent chemotherapy, followed by transplantation with cells from a related or unrelated matched donor. The median follow-up was 11.4 months, almost a year.
Orca-T significantly outperformed alloHSCT in survival free of chronic moderate to severe GvHD, or the time alive without GvHD (78% vs. 38%), meeting the study’s primary goal.
In secondary measures, more patients who received Orca-T were alive a year after the transplant than those treated with alloHSCT (94% vs. 83%). Also, the cumulative incidence of moderate to severe GvHD was about three times lower with Orca-T over alloHSCT (13% vs. 44%).
Exploratory endpoints at a year showed a slightly higher relapse-free survival rate in the Orca-T versus alloHSCT arms (76% vs. 74%). At the same time, the cumulative incidence of non-relapse mortality, or death without a relapse, was four times lower with Orca-T (3% vs. 13%). Moreover, there was a lower cumulative incidence of moderate or severe acute GvHD with Orca-T (6% vs. 17%). Severe or life-threatening infection that required urgent intervention was similar in both arms (6% vs. 10%).
“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 chief executive officer at Orca Bio. “We are working closely with the FDA and expect to submit [an approval application] this year.”
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