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Introduction Iron oxide nanoparticles have been used in preclinical and clinical research as imaging agents for decades because of their magnetic properties and their known safety profile. We have been developing the MagSense® HER2 Test Reagent (MSH2TR), a formulation of anti-human epidermal growth factor receptor 2 (HER2) conjugated iron oxide nanoparticles, for the noninvasive detection of metastatic lymph nodes to aid in staging of HER2 positive (HER2+) breast cancer patients. Currently, nodal staging requires a patient’s lymph nodes to be surgically removed or biopsied for histopathological examination. MSH2TR is currently being investigated in a first-in-human phase I study in subjects with HER2+ primary breast cancer who, in the judgment of the investigator, have a likelihood of lymph node metastasis. Methods This phase I study is designed to be a preliminary proof-of-principle study with the primary objective of achieving an initial assessment of the safety and tolerability of the MSH2TR injectable imaging agent. A secondary objective of the study is the confirmation that the route of administration is effective in allowing the imaging agent to reach the patient’s lymph nodes. The exploratory objectives of the study include a comparison of the two imaging modalities: magnetic resonance imaging (MRI) and a novel proprietary technology called magnetic relaxometry (MRX), to standard clinical tissue histopathology. The exploratory objectives are expected to provide a preliminary assessment as to whether the MagSense® HER2 imaging agent, when used with one or both imaging modalities, might be able to provide a non-invasive alternative to nodal biopsy. All eligible subjects receive a 30mg injection of MSH2TR into the subareolar interstitial tissue or area near and around the primary tumor. MRI of the axilla are performed before and 24 to 72 hours after MSH2TR injection followed by core biopsy or dissection of the suspected lymph node tissue as per standard of care (SOC) procedures for histopathology assessments and also for ex vivo MRX measurements using the MagSense® Relaxometry Instrument. Review of the MRI scans and histopathology are performed in respective central laboratories. The study is currently enrolling in 4 clinical sites in Australia. Results From an interim evaluation of the first five patients that have completed the study, MSH2TR appears to be safe and well tolerated and no safety issues reported related to the imaging agent. The imaging agent, as administered, is reaching the lymph nodes. The study intends to enroll approximately 15 patients for the preliminary efficacy assessment. Safety and efficacy results from available patients’ data will be presented. Conclusion Available data to date from the ongoing phase I study show that the MagSense® HER2 imaging agent, as administered, appear to be safe and drains to the axillary lymph nodes within the timeframe of interest. Further data collection is ongoing for the preliminary evaluation of efficacy. Citation Format: Yalia Jayalakshmi, Jane Fox, Natalie Yang, Marie Zhang, Robert Proulx, Steven Reich. Noninvasive Detection of Lymph Node Involvement in Subjects with Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer using the MagSense® HER2 Test Reagent – A First-In-Human Phase 1 Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-09-02. |
