Clinical Response to Seribantumab, an Anti–Human Epidermal Growth Factor Receptor-3 Immunoglobulin 2 Monoclonal Antibody, in a Patient With Metastatic Pancreatic Ductal Adenocarcinoma Harboring an NRG1 Fusion

Thavaneswaran et al., JCO Precision Oncology 2022
Published online December 1, 2022.

Introduction: Seribantumab is a fully human anti-HER3 IgG2 monoclonal antibody that blocks the ligand-dependent activation of HER3 and HER3-HER2 dimerization. This leads to reduced phosphorylation across the ERBB family and inhibition of the PI3K/AKT and MAPK downstream signaling pathways, resulting in tumor regression in preclinical models harboring an NRG1 fusion. Seribantumab dose-dependently inhibited phosphorylation of key signaling pathways in human pancreatic ductal epithelial cells expressing an ATP1B1-NRG1 fusion and inhibited tumor growth in a PDX model of PDAC harboring an APP-NRG1 fusion. Although preclinical data and case reports have previously described NRG1 fusions as a biomarker for other HER2-/HER3-directed therapies and there is active clinical investigation with seribantumab in this molecular subset, to our knowledge, this case report is the first characterization of seribantumab’s clinical activity in an Australian patient with an ATP1B1-NRG1 fusion, treated through compassionate access.

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