Incidences of graft versus host disease will be a focal point of the study.
Orca Bio has initiated its phase 3 clinical trial for Orca-T, an allogeneic cell therapy being evaluated for the treatment of acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and high-risk myelodysplastic syndromes (MDS).1
Precision-T (NCT05316701) is a randomized, open-label, multicenter study intended to compare the safety and efficacy of Orca-T against standard of care allogeneic hematopoietic stem cell transplant (standard allo-HSCT). Of particular interest to the investigation will be incidences of graft versus host disease (GVHD) and other transplant-related adverse events, as Orca-T has been developed with the intention of mitigating the risks of these drawbacks to standard allo-HSCT.
“By precision engineering the donor graft, we aim to create a cell therapy that retains the benefits of transplant without serious complications like graft versus host disease and disease relapse,” Robert Negrin, MD, professor of medicine, Stanford School of Medicine, said in a statement.1 “This has been demonstrated by the recent results of the Phase 1b/2 single-arm trials with Orca-T, and we are pleased to be evaluating this novel cell therapy in a randomized Phase 3 clinical trial.”
Orca-T is an engineered allograft from matched donors that consists of infusions of regulatory T-cells, conventional T-cells, and CD34+ stem cells derived from peripheral blood. It was previously granted regenerative medicine advanced therapy designation and orphan drug designation by the FDA in October 2020.2
The two-arm trial is expected to enroll 174 patients between the ages of 18 and 65 who have been diagnosed with AML, lymphoid, or mixed phenotype leukemia that is in complete remission, or with high to very-high risk or therapy-related/secondary MDS. Participants must have a cardiac ejection fraction of at least 45% at rest or a shortening fraction of at least 27%, a diffusing capacity of the lung for carbon monoxide of at least 50%, and female participants of childbearing potential must have a negative serum or urine beta-HCG test. Patients who have previously had an allo-HSCT, are currently taking corticosteroids or other immunosuppressive therapy, or have a Karnofsky performance score of less than 70% will be excluded from the study.
Patients in the experimental arm will receive Orca-T following a myeloablative conditioning regimen. Single-agent prophylaxis for GVHD will be administered after conventional T-cell infusion. Patients in the active comparator arm will receive unmanipulated standard allo-HSCT from a matched donor after a myeloablative conditioning regimen and they will receive a dual-agent prophylaxis starting on Day -3. The primary end point compares the rate of chronic GVHD-free survival. Secondary end points include GVHD and relapse-free survival, incidences of moderate to severe chronic GVHD, and relapse-free survival.
The trial is taking place at more than 20 clinical trial sites including Stanford Health Care, Winship Cancer Institute of Emory University, and Sarah Cannon Research Institute.1
“The Precision-T study is an important step forward for patients battling deadly blood cancers like AML and ALL, which are often aggressive and for which standard allo-HSCT treatment carries significant risks,” Ivan Dimov, PhD, co-founder and chief executive officer of Orca Bio added.1 “We are pleased to collaborate with these clinical trial centers and the broader blood cancer community to advance this study with the ultimate goal of delivering a safe and effective therapy to the patients who need it.”
The study has already begun treating patients. It is estimated to be completed in April 2028.