Dr Meyer on the Exploration of Orca-T With RIC in Hematologic Malignancies

“Most patients with severe hematological malignancies are older…where most patients could benefit from reduced-intensity chemotherapy conditioning. That's always been a goal of the field, to use the immune system, not the chemotherapy. It looks like Orca-T is effective in the RIC setting in terms of myeloid engraftment, overall survival, [and a] low incidence [rate] of GVHD. We’re excited about that because it opens up the treatment to many more patients.”

Everett Meyer, MD, PhD, an associate professor of medicine (blood & marrow transplantation), an associate professor of pediatrics (stem cell transplantation), and an associate professor of surgery (abdominal transplantation) at Stanford Medicine, discussed the ongoing investigation of Orca-T used with reduced-intensity conditioning (RIC) for patients with advanced hematologic malignancies.

In the phase 3 Precision-T trial (NCT05316701), Orca-T plus myeloablative conditioning improved chronic graft-vs-host disease (GVHD)–free survival compared with conventional allogeneic hematopoietic stem cell transplant and myeloablative conditioning; these data supported the granting of FDA priority review for Orca-T in this setting, with an anticipated decision for approval in July 2026.

Other studies have explored other methods for Orca-T administration, including in the context of RIC. Meyer explained that most patients with advanced hematologic malignancies are older, and as such, may not be candidates for intensive conditioning.

Data from a prior phase 1 trial (NCT05088356) showed that Orca-T with RIC produced durable efficacy outcomes and a trend toward decreased acute GVHD in patients with acute lymphocytic leukemia, acute myeloid leukemia (AML), or myelodysplastic syndromes (MDS). This study helped inform the design of the ongoing phase 2 SERENE-T trial (NCT07216443), which is examining Orca-T with RIC or nonmyeloablative conditioning in patients with AML or MDS.

Building on the phase 1 data, SERENE-T could provide valuable insight on the potential role for Orca-T with RIC, which could open up new treatment approaches for patients with hematologic malignancies who are older or sicker, Meyer concluded.