Allogeneic HSC and regulatory T cell  (Orca-T) engineered cell therapy following reduced intensity conditioning: Results of a single center Phase 1 study

作者：Alejandro Villar‐Prados, Paige Kim, Katherine Sutherland, Robert S. Negrin, Sally Arai, Matthew Frank, Laura Johnston, Robert Lowsky, David Miklos, Lori Muffly, Saurabh Dahiya, Andrew R. Rezvani, Surbhi Sidana, Parveen Shiraz, Judith A. Shizuru, Wen‐Kai Weng, Melody Smith, Sushma Bharadwaj, John Tamaresis, Anna Pavlova, James Scott McClellan, Everett Meyer · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-111 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Hematopoietic Stem Cell Transplantation、Mesenchymal stem cell research

Abstract Introduction: The combination of Orca-T, an investigational allogeneic T-cell immunotherapy, with myeloablative conditioning (MAC) has demonstrated a significant reduction of graft versus host disease (GvHD) in a randomized Phase 3 trial (NCT05316701). The impact of combining Orca-T with reduced intensity conditioning allogeneic hematopoietic stem cell transplant (RIC-HSCT) for the treatment of hematological malignancies remains an open question. Methods: This trial is a single-center, open-label, phase 1 feasibility and safety study with primary endpoints of incidence of grade III-IV GVHD, incidence of primary graft failure and donor T cell chimerism at day +60 and engraftment. Secondary endpoints include all grade acute GvHD, moderate to severe chronic GvHD, relapse free survival (RFS), non-relapse mortality (NRM), GvHD relapse free survival (GRFS) and overall survival (OS). The study has two independent trial arms depending on donor type [HLA matched related and unrelated, 8/8 HLA matched (n = 42) and 7/8 HLA mismatched (n = 7)]. The first eleven patients were conditioned with fludarabine 160 mg/m2, melphalan 50 mg/m2 and 4 Gy of total body irradiation (TBI). Fourteen subsequent patients received 10mg/kg of thiotepa instead of melphalan, with the same dosing of fludarabine and 4 Gy TBI. Conditioning was further reduced to thiotepa 5mg/kg, 3 Gy TBI with fludarabine kept at 160mg/m2where 24 patients were enrolled in this cohort. From this cohort patients, 8/8 HLA ma...