Three-year overall survival with Orca-T allogeneic T-cell immunotherapy was 86% for patients with AML, ALL and MDS compared to 67% in a non-randomized historical cohort of post-transplant cyclophosphamide (PTCy)
Reduced non-relapse mortality and increased relapse-free survival seen with Orca-T compared to PTCy at one-year
In a second oral presentation, early feasibility data were presented on the combination of Orca-T and allogeneic CAR-T cells in patients with high-risk B-ALL
Orca-T is being evaluated in a pivotal Phase 3 clinical trial versus a conventional allogeneic stem cell transplant with data expected in the first half of 2025
MENLO PARK, Calif.--(BUSINESS WIRE)--Orca Bio, a late-stage biotechnology company committed to transforming the lives of patients through high-precision cell therapy, today presented positive long-term data on its lead investigational allogeneic T-cell immunotherapy, Orca-T, at the 66th American Society of Hematology (ASH) Annual Meeting.
Three-Year Survival Data with Orca-T vs PTCy
The results of a three-year follow-up analysis with Orca-T plus single-agent tacrolimus (TAC) showed encouraging overall survival (OS) in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and high-risk myelodysplastic syndrome (MDS). These results also showed an improvement when compared to a historical cohort of patients receiving an allogeneic stem cell transplant (alloHSCT) with post-transplant cyclophosphamide (PTCy)-based graft versus host disease (GvHD) prophylaxis.
“With the current standard of care, physicians must carefully balance the risk of relapse with the risk of toxicities when treating patients with serious hematological malignancies, as both impact overall survival,” said presenting author Caspian Oliai, MD, medical director of the UCLA Bone Marrow Transplantation Stem Cell Processing Center. “The preliminary results with Orca-T have been promising, and now observational outcomes show sustained improvement in comparison to a similar cohort of patients who received a conventional alloHSCT with PTCy at one, two and three years. These data add to the growing body of evidence suggesting Orca-T could potentially offer an important new treatment option for patients.”
This analysis from the multicenter Phase 1b clinical trial evaluated a subset of patients (n=77) who received Orca-T with TAC. These outcomes were compared to patients from a CIBMTR literature-based cohort (n=293) who received alloHSCT with a PTCy-based GvHD prophylaxis regimen. All patients across both groups received myeloablative conditioning (MAC) and used a related or unrelated fully matched donor. These subsets of patients were selected based on disease, disease status and conditioning regimens that most closely resemble the patients enrolled in the ongoing pivotal Phase 3 clinical trial evaluating Orca-T.
The analysis included patients who had a median follow-up time of 33 months (range 5-54 months) and 24 months (range 0-53 months) in the Orca-T Phase 1b and PTCy cohorts, respectively. The OS at 12, 24 and 36 months (p=0.0021) are summarized in the table below:
Follow-up | Phase 1b Orca-T plus TAC OS | AlloHSCT with PTCy OS |
1 year | 96% (range 88%-99%; 95% CI) | 82% (range 78%-87%; 95% CI) |
2 year | 88% (range 78%-94%; 95% CI) | 73% (range 68%-79%; 95% CI) |
3 year | 86% (range 73-92%; 95% CI) | 67% (range 61%-74%; 95% CI) |
Further analyses of these patient subsets found Orca-T may reduce non-relapse mortality (NRM) and increase relapse-free survival (RFS) compared to PTCy. At one year, NRM was 1.4% in the Orca-T group and 7.4% in the PTCy cohort. The rate of RFS at one year was 83% and 71% for patients receiving Orca-T and PTCy, respectively. Results also found that age had no significant impact on OS at one year. For patients receiving Orca-T, OS was 95% (88%-100%) in patients under the age of 50 and 97% (92%-100%) in patients over the age of 50. For patients in the PTCy cohort, OS was 86% (81%-92%) in patients under the age of 50 and 77% (70%-85%) in patients over the age of 50.
Across all patients in the Phase 1b trial, Orca-T was manufactured reliably and delivered with vein-to-vein times of 72 hours or less across the U.S.
“We’re pleased to present positive long-term follow-up data for Orca-T as these findings provide valuable insight into how the cell therapy performs over extended periods of time,” said Scott McClellan, MD, PhD, chief medical officer at Orca Bio. “As we eagerly await the results of our pivotal Phase 3 clinical trial evaluating Orca-T in a similar patient population, we are one step closer to gathering the information needed for BLA submission and toward potentially making a significant difference for patients.”
Combining Orca Bio Approach with CAR-T Technology
A second oral presentation highlighted initial feasibility, safety and efficacy data from an investigator-sponsored Phase 1 clinical trial evaluating OrCAR-T, a platform that combines the Orca Bio technology with CAR-T technology. This presentation highlighted data following treatment with Orca-T and allogeneic CD19/CD22 CAR-T cells in patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL).
B-ALL remains incurable for many patients despite treatment with an alloHSCT or autologous CAR-T cells, which can also lead to serious complications including GvHD, infections and CAR-related toxicities. Preliminary results for 10 patients treated with OrCAR-T who reached the primary endpoint of 42 days post-treatment showed neutrophil and platelet engraftment at 14 days. At a median follow up of 381 days (range 61-762 days, including 6 patients with >12 months of follow-up) across three dose escalation levels (1x106 CAR+ cells/kg; 2x106 CAR+ cells/kg; 3x106 CAR+ cells/kg), there were no cases of acute or chronic GvHD, no grade 3 or greater cytokine release syndrome and no neurotoxicity observed.
These early findings suggest a single treatment that combines a high-precision cell therapy like Orca-T with specific CAR-T cells has the potential to benefit patients with a range of hematologic diseases.
About Orca-T
Orca-T is an investigational allogeneic T-cell immunotherapy being evaluated in clinical trials for the treatment of multiple hematologic malignancies. Orca-T is comprised of highly purified regulatory T-cells, CD34+ stem cells and conventional T-cells derived from peripheral blood from either related or unrelated matched donors. Orca-T is currently being evaluated in Precision-T, a pivotal Phase 3 clinical trial, which has completed enrollment at leading transplant centers across the U.S. Orca-T has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration.
About Orca Bio
Orca Bio is a late-stage biotechnology company developing high-precision cell therapies for the treatment of cancer and autoimmune diseases. Our investigational products are designed to replace a patient’s diseased blood and immune system with a healthy one, with the goal of improving outcomes with fewer risks than the standard of care. Our manufacturing platform uses single-cell precision to create proprietary, uniquely-defined products that have the potential to transform allogeneic cell therapy. At Orca Bio, our mission is to make curative cell therapies both more effective and safer, and in doing so, push past the field’s current boundaries and redefine its future. For more information, visit www.orcabio.com.
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