Purpose: IMC-002 is a fully human cluster of differentiation 47-targeted immunoglobulin G4 monoclonal antibody, designed to minimize off-target effects. This study (NCT05276310) assessed its safety/tolerability and preliminary anti-tumor activity in patients with advanced solid tumors who were not eligible for or had progressed on standard treatment.
Materials and methods: Here we report results from the initial 3 + 3 design dose-escalation part of a two-part Phase 1, open-label, dose-escalation/expansion study. IMC-002 was administered intravenously every 2 weeks at four doses (5, 10, 20, and 30 mg/kg). The primary objective was to assess safety/tolerability, including maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). Secondary objectives included pharmacokinetics and clinical activity, including best overall response (BOR), disease control rate (DCR), and clinical benefit rate (CBR).
Results: Twelve patients were included in total, with three per dose level. Most patients (11/12) had stage IV disease; 7/12 had received three prior systemic therapies. No dose-limiting toxicities were observed and MTD was not reached. The most common treatment-related adverse events (TRAEs) were rash (9/12), vitreous floaters (8/12), and (hemolytic) anemia (5/12). There was no treatment-related thrombocytopenia, neutropenia, or infection. IMC-002 had dose-proportional pharmacokinetics, achieving steady state levels from Cycle 2. BOR was stable disease in six patients (DCR 50.0%). CBR was 33% (four patients maintaining disease control for ≥6 months).
Conclusion: IMC-002 demonstrated favorable safety/tolerability at doses of 5-30 mg/kg every 2 weeks. RP2D was defined as 20 mg/kg every 3 weeks. Preliminary anti-tumor activity was observed, with a CBR of 33%.
Keywords: CD47; Immunotherapy; Maximum tolerated dose; Monoclonal antibody; Phase I Clinical Trial; Safety.