Abstract PS05-03: MagSense® HER2, a Molecularly Targeted Magnetic Resonance Imaging Agent for the Detection of Axillary Nodal Metastasis in Subjects with Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer

Abstract Background Precise nodal staging is critical in guiding systemic and regional treatments including surgery in the management of breast cancer. Regional nodal assessment includes axillary imaging (mostly by ultrasound) and lymph node sampling. Since imaging findings suggestive of nodal metastasis are based on size and morphologic changes and not specific to tumor type, pathologic confirmation through either biopsy or removal of sentinel lymph node (SLN) remains the gold standard. Imagion is developing the MagSense® HER2 Imaging Agent (MSH2IA), an anti-human epidermal growth factor receptor 2 (HER2) conjugated with iron oxide nanoparticles, for the detection of nodal metastasis in HER2+ breast cancer patients. MSH2IA is currently being investigated in a first-in-human phase 1 study (ACTRN12621000126819) in HER2+ breast cancer patients who are diagnosed to have suspicious nodes by conventional imaging. Methods The key objectives of the phase 1 study are safety and tolerability of MSH2IA and confirmation that MSH2IA drains to the axillary lymph nodes. The study also explores MSH2IA’s ability to detect metastatic nodes when used with magnetic resonance imaging (MRI), with tumor status assessed by standard tissue histopathology. All eligible subjects receive a 22.5 mg (iron equivalent) subareolar or peritumoral injection of MSH2IA. MRI of the axilla are obtained before and 24 to 72 hours after MSH2IA injection. Core biopsy or dissection of a node suspicious by ultrasound is obtained for histopathology assessments. After completing the first cohort of 6 subjects, the protocol was amended to include the insertion of an MRI compatible clip in a node suspicious by ultrasound to localize the suspicious node for core biopsy and postdose MRI scan. Review of MRI scans and histopathology are performed in respective central laboratories. Results Thirteen participants with HER2+ breast cancer have completed the study. MSH2IA appears safe and well tolerated. The imaging agent, as administered, is detectable by MRI and pathology, confirming that MSH2IA drains to the lymph nodes via the chosen route of administration. In postdose MRI scans, study central radiologists reported distinct and differentiable MRI appearance in morphologically normal and suspicious nodes. The presence of a distinct postdose MR image appearance was confirmed by a group of independent radiologists in a separate blinded review. While normal nodes appeared with homogeneous hypointensity, morphologically suspicious nodes showed partial irregular darkening and/or speckled heterogeneous hypointensity. In evaluable subjects, histopathology of the core biopsies obtained from the clipped nodes confirmed the presence of HER2+ nodal metastasis, providing preliminary evidence for node-level concordance between MRI vs pathology observations. Safety, imaging, and pathology results from all available subjects will be presented. This phase 1 study in Australia will be closing enrollment by July 31, 2023. A phase 2 study in the United States and elsewhere is being planned with the objectives of optimizing dose, schedule, and imaging parameters for best diagnostic performance for clinical utility. Conclusion Available data from the ongoing phase 1 study show that MSH2IA appears safe and drains to the axillary lymph nodes. MSH2IA displays a distinct and differentiable MRI appearance in nodes morphologically highly suspicious for tumor, which is confirmed to be HER2+ metastasis by histopathology by node level concordance. This data provides preliminary proof of principle for the mechanism of molecularly targeted MR imaging and suggests that MSH2IA has the potential to provide tumor-specific MR imaging not currently available in conventional axillary imaging. Citation Format: Jane Fox, Shanta Velaiutham, Natalie Yang, Eddie lau, Kowsi Murugappan, Beena Kumar, Alex Laslowski, Koushik Govindarajan, Steven Reich, Stephen Thomas, Nitika Neha, Marie Zhang, Isaac Bright. MagSense® HER2, a Molecularly Targeted Magnetic Resonance Imaging Agent for the Detection of Axillary Nodal Metastasis in Subjects with Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS05-03.