Phase 1 BSB-2002 mutant NPM1–targeted TCR-T therapy in relapsed/refractory AML

This Phase 1, open-label, dose-finding study evaluates BSB-2002, a personalized autologous T cell receptor–engineered T cell (TCR‑T) therapy whose introduced TCR recognizes a mutant NPM1 peptide presented by HLA‑A02:01 (mechanism: HLA‑restricted mutant NPM1–directed TCR-T cytotoxicity). Patients first undergo leukapheresis for manufacturing, then receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine (mechanism: DNA-damaging alkylator and purine analog/DNA synthesis inhibitor, respectively) followed by a single IV infusion of BSB-2002, with intensive response, safety, and cellular-kinetics monitoring. The eligible population is adults with relapsed or refractory NPM1‑mutated AML who are HLA‑A02:01–positive and heavily pretreated (3+ lines), a subset because HLA‑A*02:01 is common but not universal. The commercial/scientific angle is a mutation-specific TCR‑T approach in AML, where antigen selection and on-target safety are major hurdles compared with CD19 CAR‑T in lymphoid disease; this program is associated with BlueSphere Bio’s TCR‑T platform while being run at City of Hope. Today’s care for R/R NPM1‑mutated AML typically relies on salvage chemo or venetoclax-based regimens, targeted agents when relevant (e.g., FLT3/IDH inhibitors if co-mutated), and allogeneic stem cell transplant when a remission can be achieved—this study explores whether a mutation-directed cellular therapy can produce deeper remissions in a late-line setting.