1035P - Phase I dose escalation study of IMC-002, a novel anti-CD47 monoclonal antibody, in patients with advanced solid tumors

Background

IMC-002 is a fully human IgG4 antibody targeting CD47. IMC-002 induces phagocytosis of tumor cells by macrophages and significantly suppresses tumor growth in preclinical models of hematologic and solid tumors. Here we present preliminary safety, pharmacokinetics (PK), and efficacy data from ongoing phase 1 study of IMC-002 in patients with advanced solid tumors who failed to standard therapy (without priming dose).

Methods

We used a traditional 3+3 design to evaluate dose limiting toxicity (DLT) over 21 days, with 4 doses of IMC-002 (5, 10, 20 and 30 mg/kg). IMC-002 was administered intravenously once every 2 weeks until disease progression or unacceptable toxicity. Tumor assessments were performed every 6 weeks according to RECIST 1.1 criteria.

Results

As of May 2023, we enrolled 12 refractory patients (9 hepatocellular carcinoma, 2 breast cancer, 1 gallbladder cancer) with median age of 55 (range 39-73). Eleven of these patients were at stage IV with multiple distant metastases and high tumor burden. The median number of prior systemic therapy was 3 (range 1-3) and 4 patients received anti-PD-(L)1 antibody. The median interval between the last dose of previous therapy and IMC-002 was 1 month (range 1-4). No DLTs were observed across 4 dose levels. The majority of treatment related adverse events (TRAEs) were grade 1-2 (92%) and most of these events occurred during the first cycle (95%). TRAEs observed in more than 2 patients included transient vitreous floaters, skin rash, anemia and nausea. No infusion related reactions, thrombocytopenia, or neutropenia were reported. The serum exposure of IMC-002 (C_max and AUC) increased with dose, and the predicted trough concentration exceeded the minimum efficacious concentration for IMC-002 when administered at a dose of over 10 mg/kg once every 2 weeks. Among the 11 efficacy evaluable patients, 5 had stable disease with a median treatment duration of 6 cycles (range 5-12). Among them, 4 had HCC and 1 had breast cancer.

Conclusions

IMC-002 demonstrated a favorable safety profile when administered intravenously every 2 weeks up to 30 mg/kg and showed preliminary efficacy in patients with advanced solid tumors. Based on safety and PK profile, we determined the recommended phase 2 dose as 20 mg/kg.

Clinical trial identification

NCT05276310.

Editorial acknowledgement

Legal entity responsible for the study

ImmuneOncia Therapeutics, Inc.

Funding

ImmuneOncia Therapeutics, Inc.

Disclosure

H. Seon, J.K. Lee, S.Y. LEE, H.T. Kim: Financial Interests, Institutional, Full or part-time Employment: ImmuneOncia Therapeutics Inc.. All other authors have declared no conflicts of interest.