Updated safety, efficacy, pharmacokinetics, and biomarkers from the phase 1 study of IMC-002, a novel anti-CD47 monoclonal antibody, in patients with advanced solid tumors.

2642 Background: Preliminary safety and efficacy data from the phase 1a dose escalation study of IMC-002 has been reported, showing no dose limiting toxicity (DLT) across 4 dose levels. Here we present updated insight into safety, efficacy, optimal dose determination through pharmacokinetics (PK) modeling, and CD47 expression. Methods: Eligible pts had metastatic or locally advanced solid tumors that progressed following at least 1 prior systemic therapy and an ECOG PS ≤1. A traditional 3+3 design was employed to evaluate DLT over 21 days, administering 4 doses of IMC-002 (5, 10, 20 and 30 mg/kg) every 2 weeks (Q2W). Tumor assessments were performed Q6W using RECIST 1.1. Optimal dosing was determined through target-mediated drug disposition (TMDD) PK modeling, incorporating FcRn recycling. CD47 immunohistochemistry (IHC) images were analyzed with an AI analyzer (Lunit SCOPE) that can distinguish staining positivity and cell type at the single cell level. Results: A total of 12 refractory patients (hepatocellular carcinoma 9, breast cancer 2, gallbladder cancer 1) were received IMC-002 with a median follow-up of 11 months (max 19 months). All treatment related adverse events (TRAEs) were grade 1-2 (92%) and TRAEs observed with over 20% incidence included skin rash, transient floaters and anemia. After the initial exposure, there was a decrease in hemoglobin levels, but these levels subsequently recovered without the evidence of hemolytic anemia. Among the 12 efficacy evaluable patients, the disease control rate was 50.0% and the clinical benefit rate (CBR, stable disease ≥ 6 months of treatment) was 33.3% with a median treatment duration of 10 months. Based on PK modeling, 20 mg/kg Q3W was selected as optimal RP2D. In the AI analysis of CD47 IHC, the density of CD47 positive macrophages tended to be higher in case with CBR compared to non-CBR cases (mean CD47+ macrophage density: 71.0 vs 44.3/mm 2 ), while the percentage of tumor cells expressing CD47 was similar between the two groups (mean CD47+ tumor cells: 54.5 vs 59.8%). Conclusions: IMC-002 has an excellent safety profile when administered intravenously at a dose of up to 30 mg/kg every 2 weeks intravenously for max 12 months treatment. IMC-002 monotherapy demonstrates meaningful clinical benefits in refractory HCC. The density of CD47+macrophages analyzed by AI is higher in CBR patients. Clinical trial information: NCT05276310 . Table: see text