Phase I data for PMB-CT01, a B-cell activating factor receptor (BAFF-R)-targeted autologous chimeric antigen receptor (CAR) T-cell therapy, have been published in The Lancet, reporting complete responses in heavily pretreated B-cell non-Hodgkin lymphoma (B-NHL) patients — including those who had already failed CD19-directed CAR T-cell therapy — with no Grade 2 or higher toxicity observed.
Seven of nine treated patients (80%) achieved a complete response (CR). Four of those responders had progressed after prior CD19-directed CAR T-cell therapy — the so-called "CAR after CAR" population — representing four of six such patients enrolled. All CRs remained ongoing at data cutoff, with the longest exceeding 35 months. Responding patients also achieved minimal residual disease (MRD)-negative status. All cytokine release syndrome (CRS) events and the two reported immune effector cell-associated neurotoxicity syndrome (ICANS) events were Grade 1 only. The first patient enrolled in the expansion phase — who had triple-hit high-grade B-cell lymphoma following CD19 CAR T failure — also achieved a CR at first disease assessment.
PMB-CT01, developed by Irvine, California-based PeproMene Bio, Inc. and licensed from City of Hope, targets BAFF-R, a receptor expressed almost exclusively on B cells and essential for their survival. Because BAFF-R expression is not dependent on CD19, the therapy can engage tumor cells that have downregulated or lost CD19 — an important mechanism of resistance to all three currently approved CD19-directed CAR T products: Bristol Myers Squibb's Breyanzi (lisocabtagene maraleucel), Kite/Gilead's Yescarta (axicabtagene ciloleucel), and Novartis's Kymriah (tisagenlecleucel). The BAFF-R target also reduces the probability of antigen-loss escape, according to PeproMene.
The published data, reported as a Research Letter in The Lancet, represent the completed dose-escalation portion of an ongoing Phase I study (NCT05370430) in relapsed/refractory B-NHL. The trial has since expanded to multiple US centers beyond the original City of Hope site, with new cohorts enrolling patients with mantle cell lymphoma, large B-cell lymphoma, and follicular lymphoma (FL). A parallel Phase I study (NCT04690595) is evaluating PMB-CT01 in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL); interim data presented at ASH 2025 showed four of six enrolled B-ALL patients achieved MRD-negative complete remission, three of whom were CD19-negative at enrollment.