Phase I/II study of c-MET inhibitor (DE605) combined with sorafenib in patients with advanced hepatocellular carcinoma

Background: DE605 is a c-MET inhibitor that can be taken orally. Sorafenib is the only treatment that has been proven to increase overall survival rates in patients with advanced hepatocellular carcinoma (HCC). However, the effectiveness of sorafenib in a clinical setting is limited. By targeting multiple signaling pathways through combination therapy, patient outcomes may improve. This study aimed to establish the maximum tolerated dose (MTD) of DE605 when administered alongside sorafenib and to assess the safety and efficacy of this combination in treating patients with advanced HCC. Patients and methods: Patients with advanced HCC received treatment that combined increasing doses of DE605 and sorafenib. The first phase of the study aimed to establish the MTD of this combination. In the second phase, patients were treated with the MTD to assess the safety and effectiveness of the treatment. Results: In the first phase of the study, 27 patients were treated with sorafenib and increasing doses of DE605. In the second phase, 32 patients were enrolled. The MTD was determined to be 240 mg of DE605 once daily (QD) in combination with 400 mg of sorafenib twice daily (BID). Of the patients treated with the MTD, 9.4% had a partial response, 65.6% had stable disease, and 25% had progressive disease. The median time to progression was 2.5 months and the median overall survival was 11.6 months. Conclusion: The combination of 240 mg of DE605 QD and the standard dose of 400 mg of sorafenib BID showed significant clinical effectiveness in treating patients with advanced HCC. The early indications of antitumor activity suggest that further development of this combination therapy may be warranted