FDA Grants RMAT Designation to Orca-Q for High-Risk Hematologic Malignancies

The FDA has granted regenerative medicine advanced therapy (RMAT) designation to Orca-Q for the treatment of patients with high-risk hematologic malignancies, according to an announcement from Orca Bio.¹

Orca-Q is a second-generation investigational allogeneic T-cell immunotherapy composed of a proprietary combination of stem cells and specific T-cell subsets derived from healthy donors. The RMAT designation is supported by data from an ongoing phase 1 trial (NCT03802695) that is evaluating Orca-Q across 6 treatment cohorts, including patients with haploidentical donors and those receiving non-myeloablative or reduced-intensity conditioning (RIC).

Findings presented at the 2026 Transplantation & Cellular Therapy Meetings demonstrated that among evaluable patients with high-risk hematologic malignancies with haploidentical donors (n = 39), Orca-Q was successfully manufactured and administered to all patients at a vein-to-vein time of less than 72 hours.² At a median follow-up of 937 days (range, 19-1825), patients experienced 1-, 2-, and 3-year overall survival (OS) rates of 80%, 77%, and 77%, respectively. Additionally, the 1-year relapse-free survival (RFS) rate was 77%, and the 1-year graft-vs-host disease (GVHD) RFS (GFRS) rate was 72%. The non-relapse mortality (NRM) rate at 1 year was 5.8%, and the relapse incidence at 1 year was 18.2%.

Findings also showed that through day 180, 8.1% of patients experienced grade 3/4 acute GVHD occurred. No instances of moderate-to-severe chronic GVHD occurred within the first year of treatment. Grade 3 or higher infections were reported in 5.3% of patients through the first year.

"The FDA’s RMAT designation for Orca-Q recognizes the significant unmet need for patients with serious hematologic malignancies and validates the promising clinical findings from our ongoing phase 1 study,” Nate Fernhoff, PhD, co-founder and chief executive officer at Orca Bio, stated in a news release.¹ “As this is our second cell therapy candidate to receive RMAT status, we have experienced firsthand how this program can support accelerated development and enhanced communication with the FDA. With our newly expanded phase 1 study continuing to enroll patients and additional data expected later this year, we remain focused on advancing our high-precision approach to deliver an important new treatment to patients with blood cancer.”

How is the phase 1 trial being conducted?

The phase 1 study is enrolling patients 12 to 78 years of age with fully matched 8/8 HLA donors undergoing myeloablative conditioning (MAC) or non-MAC/RIC (NMA/RIC); and patients 12 to 65 years of age for those with 7/8 mismatched donors undergoing MAC.³ Patients need to have acute myeloid, lymphoblastic or mixed phenotype leukemia, or high- or very high–risk myelodysplastic syndrome either in complete remission or with a bone marrow blast cells level of no more than 10%. Patients need to be indicated for allogeneic hematopoietic stem cell transplant (allo-HSCT)

The study is excluding patients who underwent prior allo-HSCT, along with those with a planned donor lymphocyte infusion.

Orca-Q is being administered and evaluated across 6 cohorts, including:

• Arm A: Patients with HLA-identical related/unrelated donors, or 7/8 HLA unrelated donors, are receiving MAC and single-or dual-agent GVHD prophylaxis.
• Arm B: Patients with haploidentical-related donors are undergoing MAC and single-or dual-agent GVHD prophylaxis.
• Arm C: Patients with HLA-identical related or unrelated donors are being given MAC and no GVHD prophylaxis.
• Arm D: Patients with HLA-identical related or unrelated donors are receiving NMA/IRC with dual-agent GVHD prophylaxis.
• Arm E: Patients with 7/8 HLA unrelated donors are being given NMA/RIC with dual-agent GVHD prophylaxis.
• Arm F: Patients with haploidentical-related donors undergoing NMA/RIC with dual-agent GVHD prophylaxis.

The rates of dose-limiting toxicities and primary graft failure through day 28 are the study’s primary end points. Secondary end points include rates of neutrophil engraftment through day 28, platelet engraftment through day 50, secondary graft failure through day 100, chronic GVHD through day 365, NRM through day 365, GRFS through day 365, disease-free survival through day 365, and OS through day 365.

References

1. Orca Bio announces U.S. FDA Regenerative Medicine Advanced Therapy (RMAT) designation granted to Orca-Q for the treatment of high-risk hematologic malignancies. News release. Orca Bio. April 28, 2026. Accessed May 1, 2026. https://orcabio.com/orca-bio-announces-u-s-fda-regenerative-medicine-advanced-therapy-rmat-designation-granted-to-orca-q-for-the-treatment-of-high-risk-hematologic-malignancies/
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. A phase 1 study of Orca-Q in recipients undergoing allogeneic transplantation for hematologic malignancies. ClinicalTrials.gov. Updated February 23, 2026. Accessed May 1, 2026. https://clinicaltrials.gov/study/NCT03802695