KIND T

Objective: To reduce acute and long-term treatment-related toxicities, we have developed a first of its kind treatment intended to improve the safety of allo-HSCT through: 1) a TBI- and busulfan-free conditioning regimen consisting of briquilimab, rabbit ATG (rATG - Thymoglobulin), fludarabine, cyclophosphamide and rituximab - briquilimab (formerly called JSP191) is a monoclonal antibody (mAb) that targets human CD117 to deplete host HSCs enabling blood and immune reconstitution with minimal toxicity with the other agents being used for transient immune suppression to prevent immunologic rejection; 2) transplantation of TCRαβ+ T-cell/CD19+ B-cell hematopoietic grafts - a stem cell therapy that enhances donor hematopoietic and immune reconstitution while decreasing GvHD; and 3) a pre- and post-transplant monitoring protocol to maximize engraftment. All three patients in the Phase 1b portion of the study show early safety and efficacy of this approach. Briquilimab was well tolerated and all patients have shown prompt and durable donor engraftment. This data indicates that it might be possible to remove irradiation or alkylator chemotherapy from the conditioning regimen in patients with FA without matched sibling donors thus decreasing the chances for cancer predisposition in these patients that have inherited DNA repair defects.

P1, N=12, Not yet recruiting, University of California, San Francisco | Trial completion date: Dec 2028 --> Aug 2029 | Initiation date: May 2023 --> Aug 2023 | Trial primary completion date: Dec 2028 --> Aug 2029