Abcuro's Ulviprubart Shows Promising Interim Results in Rare Blood Cancer T-LGLL
核心洞察
Abcuro (搜索) presented interim Phase 1/2 data for ulviprubart in T cell large granular lymphocytic leukemia (搜索) at the ASH Annual Meeting, showing the drug was well tolerated with an acceptable safety profile.
Seven of 21 enrolled patients achieved neutropenia (搜索) response with treatment, while two patients showed anemia (搜索) response, addressing key complications of this rare blood cancer.
The first-in-class anti-KLRG1 (搜索) antibody demonstrated selective depletion of pathogenic T cells, with some patients experiencing sustained reductions of over 90% in target cell populations.
Abcuro (搜索) presented interim data from its Phase 1/2 clinical trial of ulviprubart in patients with T cell large granular lymphocytic leukemia (搜索) (T-LGLL (搜索)) at the 67th American Society of Hematology Annual Meeting, demonstrating encouraging safety and efficacy signals for this first-in-class immunotherapy targeting a rare blood cancer.
The open-label, ascending dose study enrolled 21 patients with T-LGLL (搜索) who suffered from neutropenia (搜索) and/or anemia (搜索), two serious complications of this hematological malignancy. At baseline, 95% of patients had neutropenia and 57% had anemia, conditions that can lead to frequent infections and transfusion dependence, respectively.
Clinical Efficacy Results
Among evaluable patients, seven achieved a neutropenia (搜索) response, defined as an absolute neutrophil count increase of ≥50% from baseline for ≥4 weeks or ANC levels ≥1000 cells/μL for ≥4 weeks. Additionally, two patients demonstrated an anemia (搜索) response, characterized by hemoglobin increases ≥1 g/dL for ≥4 weeks not attributable to transfusion or growth factor support.
The drug's mechanism of action showed clear biological activity, with seven patients experiencing sustained depletions of >50% of CD8+ CD57+ KLRG1 (搜索)+ T cells at two or more consecutive visits. Three patients achieved even more dramatic responses, with sustained depletions of >90% of both CD8+ CD57+ KLRG1+ T cells and the CD8+ CD57+ parent population.
"The data presented at ASH continue to support the potential of ulviprubart to selectively target and deplete highly differentiated T cells that drive debilitating diseases like T-LGLL (搜索)," said H. Jeffrey Wilkins, MD, Chief Medical Officer of Abcuro (搜索).
Safety Profile
Ulviprubart demonstrated an acceptable safety profile across ascending doses, with most treatment-related adverse events being mild or moderate in severity. Only one patient experienced a Grade 3 infusion-related reaction, which was the sole serious treatment-related adverse event observed during therapy. The drug was generally well tolerated, with 62% of patients achieving more than 12 weeks of every-four-week dosing.
Disease Background and Unmet Need
T-LGLL (搜索) is a hematological cancer characterized by clonally expanded CD8+ differentiated T cells that are frequently KLRG1 (搜索)-positive. The disease results in neutropenia (搜索) and anemia (搜索), with neutropenia leading to frequent infections that represent a major cause of premature death in these patients. Anemia results in transfusion dependence in approximately one-third of patients, significantly impacting quality of life.
Drug Mechanism and Development
Ulviprubart is a potentially first-in-class monoclonal antibody targeting KLRG1 (搜索), a cell surface receptor predominantly expressed on highly differentiated T cells. The drug is designed to selectively deplete KLRG1-expressing T cells while sparing B cells and regulatory T cells required to maintain normal immune system homeostasis.
The ongoing Phase 1/2 trial (NCT05532722) has safety and tolerability as its primary objective, with secondary objectives including evaluation of initial efficacy and pharmacokinetic/pharmacodynamic profiles. Beyond T-LGLL (搜索), ulviprubart is also being evaluated in a registrational Phase 2/3 clinical trial for inclusion body myositis (搜索), having received orphan drug designation from both the FDA and EMA for that indication, along with Fast Track designation from the FDA.