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

Aug 8, 2022
Learning objective: After reading this article, learners will be able to cite a new clinical development in GvHD.

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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*

Characteristic, % (unless otherwise stated)

Multicenter phase Ib (NCT04013685)
n = 103

Single-center phase I/II (NCT01660607)
n = 34

CIBMTR control cohort
n = 375

Median age, years (range)

51 (19–65)

42 (19–71)

52 (18–65)





Primary disease





















              Non-Hodgkin lymphoma








Graft source




              HLA-matched siblings




              HLA-matched unrelated donor




ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CIBMTR, Center for International Blood and Marrow Transplant Research; CML, chronic myeloid leukemia; HLA, human leukocyte antigen; MDS, myelodysplastic syndrome.
*Adapted from Oliai. 2022.1

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*

Outcome, % (unless otherwise stated)

Orca-T cohort

CIBMTR control cohort

Median time to neutrophil engraftment, days posttransplant


Median time to platelet engraftment, days posttransplant


Grade 3 infections (range)

10 (95% CI, 2–26)

Severe acute GvHD (range)

4 (95%CI, 0–20)

16 (95%CI, 12–19)

Moderate to severe (≥Grade 2 chronic GvHD, (range)

5 (95% CI, 0–21)

38 (95% CI, 33–44)

Relapse (range)

20 (8–34)

35 (30–40)

GvHD relapse-free survival (range)

71 (95% CI, 60–78)

21 (95% CI, 17–25)

Overall survival (range)

90 (95% CI, 82–95)

68 (95% CI, 63–73)

CI, confidence interval; GvHD, graft-versus-host disease.
*Adapted from Oliai, 2022.
As defined in the Blood & Marrow Transplant Clinical Trials Network Manual of Procedures.

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.


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.

  1. Oliai C. Orca-T, an engineered allograft, results in high GvHD-free and relapse-free survival following myeloablative conditioning for hematological malignancies. Oral abstract #S237. European Hematology Association 2022 Congress; Jun 12, 2022; Vienna, AT.
  2. Labiotech. Orca Bio announces Precision-T phase 3 study open and enrolling patients across US transplant centers. Published Aug 3, 2022. Accessed Aug 15, 2022.


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