Phase 1b dose-expansion study of IMC-002, a anti-CD47 monoclonal antibody, in patients with advanced triple negative breast cancer (TNBC).

Abstract

2524 Background: IMC-002 is a novel therapeutic agent with a distinct mechanism of action. In a phase 1a dose-escalation study, IMC-002 demonstrated favorable safety and tolerability, and clinical activity was observed in patients with hepatocellular carcinoma (HCC) in a subsequent phase 1b trial. Here, we present results from the phase 1b expansion cohort in patients with triple-negative breast cancer (TNBC), focusing on safety, efficacy, and analyses of soluble biomarkers. Methods: Eligible pts had advanced TNBC with progression after ≥1 prior systemic therapy and ECOG PS ≤1. IMC-002 (20 mg/kg Q3W) was administered in combination with gemcitabine plus carboplatin or paclitaxel and continued until disease progression. Tumor response was assessed every 6 weeks per RECIST 1.1 and iRECIST. Baseline ctDNA was analyzed using the AlphaLiquid 1000 platform (1,023 -gene panel). To exclude germline and clonal hematopoiesis of indeterminate potential (CHIP) variants, paired PBMC sequencing was performed. The assay detected single nucleotide variants (SNVs), small insertions and deletions (INDELs), fusions, copy number alterations (CNAs), microsatellite instability (MSI), and blood-based tumor mutational burden (bTMB). Results: A total of 12 pts with advanced TNBC received IMC-002 in combination with gemcitabine plus carboplatin (n=9) or paclitaxel (n=3). Most pts had received ≥2 prior systemic therapy (n=11), and ECOG PS 1 was observed in 10 pts. TRAEs reported in > 1 pt included grade 3 hematologic events, namely anemia (n=6) and hemolytic anemia (n=5). Non-hematologic TRAEs were limited to grade 1–2 and included skin rash (n=9), vitreous floaters (n=4), photopsia (n=3), and IRR (n=2). Among 12 efficacy-evaluable pts, the ORR was 25%, the DCR was 75%, and the CBR (disease control ≥ 6 months) was 42%. Exploratory ctDNA analyses identified no MSI-H tumors. One patient with a partial response was BRCA-positive. Patients achieving clinical benefit showed a higher median maximum somatic allele frequency (MSAF) than those without clinical benefit (32.65 vs 1.00; p=0.19). No clear association between bTMB and clinical activity was observed. Conclusions: IMC-002 in combination with gemcitabine plus carboplatin or paclitaxel demonstrated encouraging antitumor activity with a manageable safety profile in heavily pretreated patients with advanced TNBC. Exploratory baseline ctDNA analyses did not identify molecular features clearly associated with clinical benefit. Clinical trial information: NCT05276310 .