Abstract CT170: Initial safety and feasibility results from a first-in-human clinical trial evaluating a novel magnetic hyperthermia approach for the treatment of metastatic solid tumors
Authors: Kraus Sarah , Tal Cheri , Shalev Boaz , Eltanani Moshe , Rukenstein Pazit , Arbib Shir , Eck Michal , Khandadash Raz , Atar Shaul , Cyjon Arnoldo , Shalev Ofer 
Published: April 2023

Abstract
A novel approach for cancer therapy was developed, comprising of magnetic multicore iron oxide nanoparticles (SaNPs) and alternating magnetic field (AMF) application. SaNPs are administered IV to the patient and accumulate in tumors through the enhanced permeability and retention (EPR) effect. The patient then undergoes regional AMF application (300kHz) that is converted to thermal energy, inducing sub-ablative hyperthermic cancer cell death. Based on extensive pre-clinical testing, treatment was proven safe and biocompatible in animal models without any associated toxicities. Efficacy studies in a murine metastatic cancer model, demonstrated the ability to reduce the number and size of metastatic lesions.
Methods: A First-in-Human open label dose escalation study was designed to evaluate the feasibility and safety of treatment in patients (n=18) with advanced metastatic solid tumors. A secondary objective was to evaluate initial efficacy signs. Eligibility criteria included patients with a life expectancy of at least 30 days with measurable disease according to RECIST 1.1. The patients underwent toxicity analysis and MRI scans without contrast media before (baseline), after treatment, and at the end of the follow-up period of 1 month. Vital signs were monitored before, during, and after treatment. Measurements included ECG, oral and body surface temperatures, blood pressure, heart rate, and oxygen saturation.
Results: 3 patients were enrolled in the first cohort that received a single SaNP injection of 10% (first dose level) without AMF. No systemic toxicity was observed. 7 patients were then enrolled and SaNP was administered at the same dose followed by AMF irradiation (first dose level of 40%) of the torso area, conducted for two intervals of 5 min. each. SaNP administration procedures were successful in all cases whereas, 3 patients succeeded to complete the full treatment in accordance to the study protocol. During AMF exposure, the patients were covered with a cooling blanket and temperatures were monitored using fiber-optic sensors. There were no significant temperature deviations beside one patient, where a rise in oral temperature was noted due to the presence of dental implants which heated up. In all patients there were no significant differences in any of the vital signs post-injection nor before or after AMF except for one patient, for whom increased heart rate was observed during irradiation, returning to baseline thereafter. No treatment-related abnormal clinical pathology or urinalysis results were identified. Some fluctuations were observed, attributed to the disease stage. Although tumor response was not expected at the first dose levels, MRI and CT results for one patient showed a reduction in a breast tumor and in another patient, stable disease was reported.
Conclusion: SaNP administration either alone or followed by AMF application was not associated with any significant adverse reactions, and no clinical or humoral toxicity was observed at initial doses of 10% SaNP and 40% AMF.
Citation Format: Sarah Kraus, Cheri Tal, Boaz Shalev, Moshe Eltanani, Pazit Rukenstein, Shir Arbib, Michal Eck, Raz Khandadash, Shaul Atar, Arnoldo Cyjon, Ofer Shalev. Initial safety and feasibility results from a first-in-human clinical trial evaluating a novel magnetic hyperthermia approach for the treatment of metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT170.