Primary analysis of a phase 1/2 study of LM-101: An anti-SIRPα antibody as a single agent in patients with advanced malignancies.

2640 Background: LM-101 is a humanized monoclonal antibody which binds to both V1 and V2 isoforms of SIRPα that expressed on macrophages and dendritic cells and enables phagocytosis of tumor cells. LM-101 has shown optimal pre-clinical safety profiles and promising anti-tumor activity in animal models. Here we report the primary analysis of the single agent dose escalation results of a phase 1/2 study (NCT05615974). Methods: This is an open-label, phase 1/2, first-in-human, multicenter dose escalation study with dose expansion evaluating safety and clinical activity of LM-101 as a single agent in patients with advanced malignancies. Eligible patients were aged ≥ 18 years with advanced solid tumors or relapsed/refractory lymphoma who had progressed on standard therapy, or intolerable to the available standard therapy, or had no available standard therapy for treatment. In the dose escalation part, enrolled patients were administered with LM-101 intravenously every three weeks at dose levels of 3 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg, and 40 mg/kg as per traditional 3+3 design. The objectives for this dose escalation part included safety and clinical activity as per RECIST v1.1 criteria or Lugano 2014 criteria. Results: As of January 24, 2024, 17 patients were enrolled in the single agent dose escalation part. No DLT was observed at all dose levels and MTD for single agent was not reached. The most frequent adverse event (AE) related to the study drug was lymphocyte counts decreased. Two patients experienced grade ≥ 3 AEs which were related to LM-101. Out of 16 patients from single agent dose-escalation groups who had at least one time tumor assessment post treatment, one patient achieved complete response (CR), one patient achieved partial response (PR) and five patients achieved stable disease (SD). Conclusions: LM-101 monotherapy showed excellent safety profile and promising anti-tumor activity in patients with advanced malignancies. Further investigation of LM-101 as a single agent and in combination with other anti-tumor agents are ongoing. Clinical trial information: NCT05615974 .