PeproMene Bio, Inc. has announced that the first patient treated in its Phase 1 clinical trial of PMB-CT01 (BAFFR-CAR T Cells) for relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) has achieved complete remission one month post-treatment. The trial is being conducted at City of Hope, where the therapy was also developed.
The patient, who had relapsed B-ALL after prior treatment with chemotherapy and blinatumomab, experienced low-grade treatment-emergent toxicities, including grade 1 cytokine release syndrome (CRS) that resolved without intervention, and no immune effector cell-associated neurotoxicity syndrome (ICANS). Notably, the patient's relapsed disease was CD19- and CD22-negative, indicating very limited available therapeutic options.
Clinical Outcomes
Ibrahim T. Aldoss, M.D., City of Hope associate professor and principal investigator of the trial (NCT04690595), stated, "He tolerated the treatment of BAFFR-CAR T Cells really well with only minimal and anticipated toxicities. Additionally, he achieved complete remission and clearance of minimal residual disease (MRD), indicating an excellent response to this effective therapy."
PMB-CT01: A Novel Approach
PMB-CT01 is a first-in-class, autologous CAR T-cell therapy that targets BAFFR (B Cell Activating Factor Receptor). BAFF-R, a member of the tumor necrosis factor (TNF) receptor superfamily, is primarily expressed on B cells and is crucial for B-cell survival. This makes it unlikely for tumor cells to evade immune responses through BAFF-R antigen loss. The CAR T-cell is constructed using anti-BAFF-R scFv antibodies with CD3ζ and 4-1BB signaling domains.
Hazel Cheng, Ph.D., COO of PeproMene, highlighted the significance of the findings: "PeproMene has achieved an exceptional milestone in the development and evaluation of PMB-CT01 with the observation of the acceptable safety profile and complete response in this PMB-CT01 treated B-ALL patient. These initial clinical outcomes are supported by City of Hope preclinical research data published in Science Translational Medicine in 2019, which shows BAFFR-CAR T Cells can effectively eliminate various B-cell malignancies including B-ALL and different subtypes of B-lymphomas."
Background on BAFFR-CAR T-cell Therapy
Preclinical research has demonstrated that BAFFR-CAR T cells can effectively eliminate various B-cell malignancies in vitro and in animal models. PeproMene has licensed intellectual property related to PMB-CT01 from City of Hope.
The ongoing Phase 1 clinical trials are evaluating PMB-CT01 in patients with relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL; NCT04690595) and B-cell Non-Hodgkin's lymphoma (B-NHL; NCT05370430).
