Orca-T and Orca-Q Set the Stage for the Future for GVHD Management in Hematologic Malignancies

Highly anticipated clinical trials and improvements in graft-vs-host disease (GVHD) management across several patient subgroups surround Orca products like Orca-T and Orca-Q for use in patients with hematologic malignancies, according to Sagar S. Patel, MD.

In an interview with OncLive®, Patel touched on evidence from trials evaluating Orca-T and Orca-Q, where Orca-T may fit into the hematologic malignancy treatment paradigm following its anticipated approval, plans for the future development of Orca-Q, and for which patient populations the platform may hold the most promise.

Patel first underscored role of the phase 2 SERENE-T trial (NCT07216443), which is currently undergoing enrollment and is evaluating Orca-T following reduced-intensity conditioning (RIC) or nonmyeloablative conditioning in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).¹ Data from the trial will be crucial in determining how wide the net of Orca-T applications can be cast, Patel added.

Patel also highlighted data with Orca-Q in patients with high-risk hematologic malignancies from a phase 1 trial (NCT03802695) that were presented at the 2026 Transplantation and Cellular Therapy Meetings (TCT).^2,3 The trial is enrolling patients with high-risk hematologic malignancies with haploidentical donors. Data presented from 39 evaluable patients treated with Orca-Q showed 1-, 2-, and 3-year overall survival rates of 80%, 77%, and 77%, respectively. Moreover, grade 3 or 4 acute GVHD occurred in 8.1% of patients at day 180 of the trial, but no patients experienced GVHD that was moderate to severe within the first year of treatment.

Looking for more expert insights on Orca-T? Make sure you check out another conversation we did with Patel regarding an analysis of the phase 3 Precision-T study (NCT05316701) and a phase 1b study (NCT04013685), which compared Orca-T with post-transplant cyclophosphamide following allogeneic hematopoietic stem cell transplant in patients with hematologic malignancies.

Patel is an associate professor of internal medicine in the Division of Hematology & Hematologic Malignancies at the University of Utah Huntsman Cancer Institute in Salt Lake City.

OncLive: What was the rationale for evaluating Orca-T following RIC or nonmyeloablative conditioning in hematologic malignancies?

Patel: This is a natural evolution based on the success of the original Orca-T platforms, which were primarily focused on using a myeloablative regimen for myeloid diseases. We’ve seen such positive data to date across the various prospective studies with Orca-T, [such as] Precision-T. SERENE-T is a follow-up, multicenter, open-label study that will look at the use of this same [Orca-T] platform, but now in a reduced-intensity and non-myeloablative context.

[The SERENE-T outcomes are] going to be key for patients who are potentially older, where we’re often reaching for [a higher] level of intensity. This [trial is] restricted to patients with AML and MDS. This will be a nice way for us to continue to see the broader application expansion of this Orca platform.

Where might Orca-T fit into clinical practice? What should hematologists who are looking to use Orca-T know about the treatment?

If [Orca-T] becomes approved, it will be a big change [compared with] the typical menu of options we’ve had as allogeneic transplanters. The ability to use a single agent for GVHD prophylaxis and elicit upfront graft manipulation to significantly reduce rates of GVHD is attractive. Even though we’ve gotten better at managing GVHD, it's still a disease associated with significant morbidity and mortality. [Thus], efforts to prevent or reduce the incidence and severity of it are welcome. [The approval of Orca-T] will be attractive on a large scale.

What other notable data with the Orca platform read out at TCT 2026?

The Orca-Q platform is used in the haploidentical setting. We are doing increasingly larger numbers of [haploidentical transplants] since not all of our patients have access to a matched-related or matched-unrelated donor. [In a phase 1 trial (NCT03802695)], the Orca-Q platform in the haploidentical donor setting yielded high engraftment rates and low incidences of severe, acute, and chronic GVHD. [These data] support the safety and efficacy of Orca-Q in reducing GVHD without the compromise of potential relapse. This early-phase study is well poised for subsequent follow-up in a larger prospective study for evaluation of the efficacy [of Orca-Q] compared with standards of care.

References

1. Trial of Orca-T following reduced intensity or nonmyeloablative conditioning in patients with acute myeloid leukemia or myelodysplastic syndrome. ClinicalTrials.gov. Updated February 23, 2026. Accessed April 8, 2026. https://clinicaltrials.gov/study/NCT07216443
2. Salhotra A, Srour S, Abedi M, et al. Preliminary safety and efficacy of myeloablative Orca-Q in patients with haploidentical donors. Presented at: 2026 Transplantation & Cellular Therapy Meetings; February 4-7, 2026; Salt Lake City, UT. Abstract 345.
3. Orca Bio presents new data at the 2026 Tandem Meetings of ASTCT and CIBMTR reinforcing Orca-T as a durable, high-precision cell therapy for hematological malignancies. News release. Orca Bio. February 5, 2026. Accessed April 8, 2026. https://orcabio.com/orca-bio-presents-new-data-at-the-2026-tandem-meetings-of-astct-and-cibmtr-reinforcing-orca-t-as-a-durable-high-precision-cell-therapy-for-hematological-malignancies/