Lancet Publishes Phase 1 Data for PeproMene's BAFF-R CAR T: 80% Complete Response, Grade 1-Only Toxicity
核心洞察
PeproMene Bio (搜索)'s BAFF-R (搜索)-targeted CAR T-cell therapy PMB-CT01 achieved complete responses in seven of nine heavily pretreated relapsed or refractory B-cell non-Hodgkin lymphoma (搜索) patients in Phase 1.
Four of six patients who had progressed after prior CD19 (搜索)-directed CAR T-cell therapy responded, with all complete responses ongoing at data cutoff and the longest exceeding 35 months.
All cytokine release syndrome events and the two reported ICANS events were Grade 1 only, a profile the company says may support future outpatient administration.
PeproMene Bio (搜索) has published Phase 1 results in The Lancet for PMB-CT01, a first-in-class B-cell activating factor receptor (BAFF-R (搜索))-targeted autologous chimeric antigen receptor (CAR) T-cell therapy, showing durable complete responses in heavily pretreated relapsed or refractory B-cell non-Hodgkin lymphoma (搜索) (B-NHL), including in patients whose disease had progressed after CD19 (搜索)-directed CAR T-cell therapy.
The data, reported as a Research Letter titled "BAFF-R (搜索) CAR T-cell therapy for relapsed or refractory B-cell lymphomas," cover the completed dose-escalation portion of an ongoing Phase 1 study (NCT05370430). Seven of nine treated patients (80%) achieved a complete response (CR). Among the so-called "CAR after CAR" population — patients who had progressed after prior CD19 (搜索)-directed CAR T-cell therapy — four of six enrolled patients responded. All complete responses remained ongoing at data cutoff, with no relapses observed and the longest ongoing complete response reaching 35 months. Responding patients also achieved minimal residual disease (MRD)-negative status.
Safety Profile Distinguished From Approved CD19 CAR T Products
All cytokine release syndrome (CRS) events and the two reported immune effector cell-associated neurotoxicity syndrome (ICANS) events were Grade 1 only, with no Grade 2 or higher toxicity observed. That profile contrasts with the three currently approved CD19 (搜索)-directed CAR T products — Bristol Myers Squibb (搜索)'s Breyanzi (lisocabtagene maraleucel), Kite/Gilead's Yescarta (axicabtagene ciloleucel), and Novartis's Kymriah (tisagenlecleucel) — which carry black box warnings for severe CRS and neurological toxicity.
"Publishing these peer-reviewed data in The Lancet represents a significant recognition of this novel therapy," said Larry W. Kwak, M.D., Ph.D., scientific founder of PeproMene Bio (搜索). "With the lack of any relapses, we believe PMB-CT01 is a paradigm-shifting CAR T-cell option for blood cancers which were previously thought to be incurable. Its elite safety may also enable outpatient administration — improving access for underserved patients — while also opening doors for treating autoimmune diseases where B-cell depletion is already proven."
PeproMene has said the safety data may support future outpatient administration, a logistically meaningful distinction given the inpatient infrastructure currently required for commercial CAR T delivery. These are company assertions based on Phase 1 data in nine patients.
Targeting a Resistance Mechanism
PMB-CT01 targets BAFF-R (搜索), a receptor expressed almost exclusively on B cells and essential for their survival. Because BAFF-R expression is not dependent on CD19 (搜索), the therapy can engage tumor cells that have downregulated or lost CD19 — an important mechanism of resistance to approved CD19-directed CAR T products. According to PeproMene, the BAFF-R target also reduces the probability of antigen-loss escape. The company licensed intellectual property relating to PMB-CT01 from City of Hope (搜索).
"These early results are encouraging, particularly for patients whose disease progressed after CD19 (搜索) or CD20-directed T-cell therapy," said Stephen Forman, M.D., paper co-author and director of the Hematologic Malignancies Institute at City of Hope (搜索). "City of Hope will continue to support the trial as the coordinating center and manufacturing site in addition to patient enrollment."
Expansion to Multiple Sites and Additional Lymphoma Subtypes
The Phase 1 trial has expanded from the original single site at City of Hope (搜索) to multiple additional medical centers across the United States. New cohorts are enrolling patients with mantle cell lymphoma (搜索), large B-cell lymphoma (搜索), and follicular lymphoma (搜索) (FL). The first patient treated in the expansion phase — who had triple-hit high-grade B-cell lymphoma following progression after CD19 (搜索)-directed CAR T-cell therapy — also achieved a complete response at the first disease assessment.
A parallel Phase 1 study (NCT04690595) is evaluating PMB-CT01 in relapsed or refractory B-cell acute lymphoblastic leukemia (搜索) (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 (搜索)-negative at enrollment.
Follicular Lymphoma Funding and Regulatory Status
In December 2024, the Institute for Follicular Lymphoma Innovation (搜索) (IFLI) committed up to USD 11 million to support the clinical development of PMB-CT01 in patients with relapsed or refractory follicular lymphoma (搜索). Novartis's Kymriah is currently the only approved CAR T therapy in FL, and no BAFF-R (搜索)-directed therapy has reached regulatory filing in any indication.
"For patients whose lymphoma returns after CD19 (搜索)-directed CAR T-cell therapy, a new target can mean a new chance. IFLI is proud to support PeproMene Bio (搜索) in advancing BAFF-R (搜索) CAR T-cell therapy and encouraged by these early, durable responses," said Mehrdad Mobasher, M.D., M.P.H., Executive Partner at the Institute for Follicular Lymphoma Innovation (搜索).
PeproMene has not disclosed a timeline for a biologics license application. The company is a clinical-stage biotech based in Irvine, California, developing therapies for cancers and immune disorders.