ASH 2024 | Observational comparison of the overall survival of patients receiving Orca-T versus PTCy

We recently completed a Phase III trial of Orca-T, comparing that to standard myeloablative conditioning and allo-transplant. And the enrollment has been completed. And as we wait for the early readout of that data, which should come up sometime next year, at ASH this year, I presented our longest-term follow-up to date of our phase Ib trial using Orca-T in the myeloablative setting with single-agent GvHD prophylaxis of tacrolimus. 

The background of Orca-T is that this is a high-precision immune therapy composed of stem and immune cells derived from an allogeneic donor that leverages a highly purified and polyclonal T-regulatory cell population that is capable of controlling alloreactive immune responses. In comparison, the standard allograft of hematopoietic cell transplantation typically administers all of the cell types at once in a single infusion. In comparison, the Orca-T strategy selects and separates into three distinct components. Number one, hematopoietic stem cells that are infused on day zero. Number two, purified T-regulatory cells that are also given on day zero but in separate infusion. And number three, conventional T-cells at a reduced dose that are infused on day plus two. This separation allows for the regulatory T-cells to migrate to the solid organs first. So, by the time the conventional T-cells arrive, an immune barrier is in place that mitigates graft-versus-host disease and also optimizes the graft-versus-leukemia effect by means of Tregs allowing conventional T-cell activation without extensive proliferation. 

So the Phase Ib trial presented at ASH this year was our longest follow-up to date of Orca-T. It included 154 patients with AML, ALL, or MDS, and all these patients received myeloablative conditioning with a KPS of 70 or greater and a comorbidity index of 4 or less. And out of the 154 patients, three developed primary graft failure. The rate of severe acute graft-versus-host disease was only 5%, and moderate to severe chronic graft-versus-host disease was only 13%, and this led to a favorable non-relapse mortality of 9%. Again, the median follow-up was 30 months, and that led to a three-year overall survival of 76% of patients with Orca-T. So very favorable follow-up there. 

The current study also put an interesting perspective on our longest follow-up to date, in that we did an observational analysis of selected patients from the original Phase Ib Orca-T trial to a PTCy cohort that was obtained from a published CIBMTR registry study. So from both original studies, we selected a patient sample who would have been eligible for the Phase III Orca-T trial, and then compared them. And we used a log rank test to see if there was any difference in overall survival amongst the treatment groups. And what we found was that overall survival was significantly better with Orca-T in comparison to a similar cohort of patients who received PTCy, corresponding to a p-value of 0.002. So it’s interesting to put this in the perspective of two emerging strategies in myeloablative conditioning setting, which can lower the non-relapse mortality to around 10% and lower. One utilizes an interesting immune therapy that’s novel, plus tacrolimus, single-agent GvHD prophylaxis, and then the other strategy uses triple agent GvHD prophylaxis, including a chemotherapy.

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