Phase 3 Data Highlight Orca-T’s Clinical Benefits in Heme Malignancies

In newly published data of the phase 3 Precision-T trial (NCT05316701), the investigational allogeneic T-cell immunotherapy Orca-T improved survival free from chronic graft-vs-host disease (GVHD), with safety and quality-of-life (QOL) advantages over conventional allogeneic hematopoietic stem cell transplant (alloHSCT) in patients with hematologic malignancies.^1,2

Initially reported in October, the trial met its primary end point of survival free from moderate-to-severe chronic GVHD (cGFS), marking the first demonstration of efficacy with a regulatory T cell (Treg)-based immunotherapy.²

Among patients with malignancies including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS), treatment with Orca-T plus single-agent tacrolimus yielded a significant improvement in cGFS. At 1 year, the estimated cGFS was 78% (95% CI, 65.0%–86.6%) among those receiving Orca-T vs 38.4% (95% CI, 26.2%–50.5%) among those receiving conventional alloHSCT with tacrolimus and methotrexate (Tac/MTX; HR, 0.26; 95% CI, 0.14–0.47; P <.001).

Additionally, interim analysis of the trial’s secondary end point of overall survival (OS) showed a trend favoring Orca-T, with 1-year estimated OS of 93.9% (95% CI, 85.8%–97.4%) and 83.1% (95% CI, 72.9%–89.8%) for Orca-T and alloHSCT, respectively (HR, 0.49; P =.12). Primary analyses for the secondary end points, including OS and GVHD and relapse-free survival, are forthcoming, according to the authors.

Better safety outcomes were also observed with Orca-T vs alloHSCT and remained consistent with previous studies. There were lower rates of infectious complications with Orca-T compared with alloHSCT; in the Orca-T group, there were 10 grade 3 infections vs 26 in the alloHSCT group. There were also lower rates of serious treatment-emergent adverse events (AEs) in the Orca-T group vs alloHSCT group (38.6% vs 56.4%).

“Today, treating patients with serious blood cancers using conventional allogeneic stem cell transplants often forces a difficult risk–benefit trade-off, as clinicians work to cure the disease while avoiding life-threatening complications like GVHD,” said Everett Meyer, MD, PhD of Stanford Medicine and lead author of the Blood publication, in a news release.¹ “The Precision-T results showed that Orca-T can meaningfully shift that balance, delivering improved GVHD-free survival alongside less toxicity, including fewer serious infections and lower nonrelapse mortality. Orca-T has the potential to become an important new therapy for patients and a valuable new option for the providers who care for them.”

Exploratory Analysis: Patient Reported Outcomes

New data from an exploratory analysis of the trial recently presented at the 67^th American Society of Hematology (ASH) Annual Meeting provided new insights into the comparative health-related QOL and hospitalization patterns with Orca-T vs alloHSCT.³ Significantly, rehospitalization due to AEs were less frequent in the Orca-T group (27.3% vs 45.7%), with fewer hospitalization days per patient (30.6 vs 40.8), fewer intensive care unit stays, lower likelihood of rehospitalization, and lower rates of nonrelapse mortality vs those receiving alloHSCT.

In a July 2025 interview with Targeted Oncology, Amandeep Salhotra, MD, assistant professor in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, commented on this observation, which was also noted in earlier Precision-T data.

“This decrease impacts [QOL] by reducing the burden of hospital stays, whether due to infections or GVHD—both more common in the standard-of-care arm,” Salhotra said during the interview. “It also reduces economic costs. Ultimately, fewer rehospitalizations may contribute to the trend toward improved [OS].”

About Orca-T

Orca-T is an investigational allogeneic T-cell immunotherapy made of individually formulated hematopoietic stem and progenitor cells, high-purity Tregs, and conventional T cells, manufactured for each patient from the mobilized peripheral blood of a specific, unique donor.⁴

The agent has amassed several FDA recognitions, including regenerative medicine advanced therapy and orphan drug designations for the prevention of GVHD or death in patients eligible for hematopoietic stem cell transplant. Currently, Orca-T’s biologics license application for use in patients with hematologic malignancies is currently under priority review by the FDA, with a Prescription Drug User Fee Act (PDUFA) target action date of April 6, 2026.

“Having [treated patients in the study], I can say the transplant course has [been safer]—less acute and chronic GVHD. If Orca-T receives approval, I envision it being used for patients eligible for myeloablative conditioning with high-risk AML, ALL, or MDS,” Salhotra said. “While [OS] was not significantly different yet… there was a trend toward improved survival. It will be important to see if those curves separate at the 2- or 3-year mark. Future studies using the Orca-T product in the reduced intensity setting would be of interest to transplant physicians like [me].”

With the FDA’s pending regulatory decision, April 2026 will be pivotal to clarifying this novel cell therapy’s role in addressing this serious complication of alloHSCT.

About Precision-T

The Precision-T study is a phase 3, randomized, open-label, multicenter study evaluating the efficacy, safety, and tolerability of Orca-T vs conventional alloHSCT across various hematologic malignancies.⁴ The study has enrolled 187 adult patients with hematologic malignancies including AML, ALL, MDS, and mixed-phenotype acute leukemia (MPAL) across 19 centers in the United States.

Patients were randomized 1:1 to receive either alloHSCT plus Tac/MTX (n = 94) or Orca-T with single-agent tacrolimus (n = 93). Both groups received myeloablative conditioning with a related or unrelated matched donor.

REFERENCES

1. Orca Bio announces Orca-T® phase 3 data published in Blood demonstrate significant improve4ment in survival free from chronic graft-versus-host disease in patients with hematological malignancies. News release. Orca Bio. December 16, 2026. Accessed December 16, 2025. https://tinyurl.com/yp839hcd

2. Meyer E, Salhotra A, Gandhi A, et al. Orca-T versus allogeneic hematopoietic stem cell transplantation (PRECISION-T): a multicenter, randomized phase 3 trial. Blood. Published online December 12, 2025. doi:10.1182/blood.2025031313

3. Orca Bio presents new clinical data on Orca-T® in older patients using reduced-intensity conditioning plus new analyses from the Precision-T phase 3 study at the 67th ASH Annual Meeting. News release. Orca Bio. December 6, 2025. Accessed December 17, 2025. https://tinyurl.com/fr56zpnr

4. Precision-T: a randomized study of Orca-T in recipients undergoing allogeneic transplantation for hematologic malignancies (Orca-T). ClinicalTrials.gov. Updated September 26, 2025. Accessed December 16, 2025. https://clinicaltrials.gov/study/NCT05316701