Development and regulatory approval of a new systemic targeted therapy for advanced hepatocellular carcinoma.

613 Background: There are no commercially available devices for the treatment of patients with advanced hepatocellular carcinoma who have failed 1st line and 2nd line therapy. We have identified tumor-specific modulation frequencies in patients with advanced hepatocellular carcinoma. We exposed patients to radiofrequency electromagnetic fields, which are amplitude-modulated from 0.1 Hz to 100 kHz and measured changes in pulse pressure. Frequencies eliciting measurable changes in pulse pressure were selected as tumor-specific frequencies. Methods: Treatment is administered to patients with advanced hepatocellular carcinoma by means of a battery-operated portable device emitting 27 MHz radiofrequency electromagnetic fields, which are amplitude-modulated at hepatocellular carcinoma frequencies. The device is connected to a coaxial cable ending with a spoon-shaped antenna placed on the anterior part of the patient's tongue during treatment. Treatment is administered three times a day for one hour. Results: A total of 69 patients with advanced hepatocellular carcinoma received treatment with the TheraBionic device until progression or death. The median overall survival of patients who received treatment with the TheraBionic device after failing 1st line and 2nd line therapy was 9.15 (95% CI 1.6-34.8) months and the median overall survival of Child-Pugh A patients was 9.5 months, which are comparatively longer than the 7.8 months pooled estimated medians of the placebo arms of 11 randomized 1st line and 2nd line placebo-controlled studies assessing the safety and efficacy of new agents for the treatment of Child-Pugh A advanced HCC (Llovet, Montal et al., J Hepatol 2019). We also analyzed the survival of patients who had received two lines of systemic therapy and did not receive any additional cancer treatment while and after receiving treatment with the TheraBionic device. The median OS of these patients was 9.8 months and the median OS of the Child-Pugh A patients was 17.2 months, which are comparatively longer than the 7.74 months pooled estimated medians of the placebo arms of the above cited 11 randomized studies. To assess unknown device-related adverse events, we assessed patient reported symptoms using the same scale in the SHARP and Asian Pacific Sorafenib studies. The incidence of any grade adverse events among Child-Pugh A who received treatment with the TheraBionic device was not different from the Placebo group of the SHARP and Asian Pacific Sorafenib studies. There were no NCI Grade 2, 3 or 4 toxicities. One patient developed grade 1 mucositis and one patient developed grade 1 fatigue. Conclusions: The data presented here provide reasonable assurance of safety and probable benefit in patients with advanced hepatocellular carcinoma who have failed 1st line and 2nd line therapy: https://www.fda.gov/medical-devices/recently-approved-devices/therabionic-p1-h220001 .