Updated results from a phase Ib and phase I/II trial of Orca-T

During the 27th Congress of the European Hematology Association (EHA2022), Caspian Oliai¹ presented updated results of a multicenter phase Ib trial (NCT04013685) and single-center phase I/II trial (NCT01660607) studying Orca-T, an engineered Treg donor product, for use in patients with hematologic malignancies. In comparison with traditional hematopoietic stem cell transplantation, the use of Orca-T may reduce the incidence of graft-versus-host disease (GvHD).¹ The GvHD Hub has previously reported on the initial results of these trials. The Phase III trial is now open and enrolling patients across more than 20 clinical trial sites.² 

Study design¹

The data includes 137 patients who have been dosed with Orca-T, with ≥100 days of follow-up, in comparison to a historical control Center for International Blood and Marrow Transplant Research (CIBMTR) cohort. The primary objective of these studies was to evaluate the safety of Orca-T, with primary endpoints measured by incidence and severity of acute GvHD (aGvHD; Grade 3 or 4), and incidence of primary graft failure. Key eligibility criteria for enrollment in the studies included using an 8/8-matched related or unrelated donor, a hematopoietic cell transplant comorbidity index of ≤4, a Karnofsky performance status score of ≥70, adequate organ function, and an age of 18–65 years (18–72 years for patients with non-Hodgkin lymphoma). Patient characteristics are shown in Table 1.

Table 1. Key patient characteristics of NCT04013685 and NCT01660607, compared with a CIBMTR historical control cohort*

Safety and efficacy¹

Outcomes in patients post infusion, compared with the CIBMTR control cohort, are shown in Table 2. All outcomes are at 1 year, apart from time to neutrophil and time to platelet engraftment, which were at days posttransplant.

Table 2. Outcomes after infusion of Orca-T, compared with a CIBMTR historical control cohort*

These studies also highlighted that the choice of conditioning regimen used alongside Orca-T may improve relapse-free survival. Patients given a conditioning regimen of busulfan with either cyclophosphamide or fludarabine had an average relapse-free survival of 72% compared with 91% in patients who received a regimen of busulfan with fludarabine and thiotepa. This may be due to improved lymphodepletion with use of thiotepa, allowing for a more favorable immune reconstitution in patients.

Conclusion

Following these phase Ib and phase I/II trials, a multicenter phase III trial (NCT05316701) of Orca-T is now opening at centers in the US, investigating Orca-T plus tacrolimus versus unmanipulated allograft plus tacrolimus and methotrexate. Results from these initial studies are promising, with Orca-T resulting in lower rates of GvHD, improved GvHD relapse-free survival, and low rates of infection when compared with a historical traditional hematopoietic stem cell transplantation control group. The phase III study will provide further insight into the safety and efficacy of Orca-T compared with the current standard of care.