Phase 1 BSB-2002 mutant NPM1–targeted TCR-T cellular therapy in R/R AML

This Phase 1, multicenter, open-label, non-randomized dose-escalation/expansion study tests BSB-2002 for adults with relapsed or refractory acute myeloid leukemia whose leukemia harbors an NPM1 mutation and who are HLA-A02:01 positive. BSB-2002 (BlueSphere Bio) is a genetically modified autologous T-cell therapy engineered to express a T-cell receptor (TCR) that recognizes an HLA-A02:01–restricted peptide derived from mutant NPM1, aiming to direct patient T cells to kill NPM1-mutant AML blasts. Patients receive lymphodepleting chemotherapy with fludarabine (a purine analog that impairs DNA synthesis) plus cyclophosphamide (an alkylating agent that crosslinks DNA) before BSB-2002 infusion, with dose-finding to determine a recommended dose and an expansion cohort to better characterize activity and safety. The key commercial/scientific angle is “public” neoantigen targeting (mutant NPM1) with an HLA-restricted TCR-T approach—potentially more tumor-specific than many surface-antigen strategies, but limited to the HLA-A*02:01 subset (roughly ~40% in people of European ancestry). Today’s care for 3rd-line+ R/R AML is sequential salvage regimens (often venetoclax-based combinations when feasible), targeted agents when actionable mutations exist, and clinical trials; durable control often relies on allogeneic transplant when a remission can be achieved, and this study explores whether a precision TCR-T approach can deepen responses and reduce relapse risk in this molecularly defined group.