HEPANOVA: Final efficacy and safety results from a phase 2 study of Tumor Treating Fields (TTFields, 150 kHz) concomitant with sorafenib in advanced hepatocellular carcinoma

Background Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable medical device. TTFields are approved by the FDA for the treatment of glioblastoma and malignant pleural mesothelioma. In vitro and in vivo TTFields at 150 kHz reduced the proliferative potential of hepatocelluar carcinoma (HCC) cell lines. In patients with Barcelona clinic liver cancer (BCLC) stage C or stage B following failure of loco-regional treatments, systemic therapies are the standard of care in eligible patients. Most HCC patients are not amenable to curative therapies and are treated with best supportive care following failure of loco-regional treatment options. The HEPANOVA EF-30 Phase II trial (NCT03606590) was a prospective study investigating the efficacy and safety of TTFields as a treatment option for advanced HCC concomitant with sorafenib. We present the finaly efficacy and safety data of the HEPANOVA trial. Trial design Patients (N=25) with unresectable HCC, amenable to systemic therapy with sorafenib following failure of loco-regional treatment options were enrolled in this study. Patients had ECOG score 0-2; Barcelona clinic liver cancer (BCLC) stage 0-C, Child-Turcotte-Pugh score between 5 and 8 points and measurable disease per RECIST. Implanted electronic devices in the torso was exclusionary. Standard sorafenib treatment was administered 400 mg (2 x 200 mg tablets). TTFields (150 kHz) were delivered for 18 hours/day until local disease progression (RECIST). Clinical follow up was performed q4w, with CT/MRI scan q12w. Primary end point was overall response rate (ORR); secondary: in-field control rate, 12-month progression-free survival rate 12 month (PFS12), 1-year OS rate and incidence and severity of adverse events (AE). A sample size of 25 patients would achieve 77% power at 0.05 one-sided alpha to detect overall radiological response rate of 20% in TTFields-treated patients. The final safety and efficacy results of the HEPANOVA trial are currently under final analyses. Our hypothesis is that treatment with TTFields as a novel modality for HCC will be efficacious and safe in treatment of advanced HCC. Methods Patients (N=25) with unresectable HCC, amenable to systemic therapy with sorafenib following failure of loco-regional treatment options were enrolled in this study. Patients had ECOG score 0-2; Barcelona clinic liver cancer (BCLC) stage 0-C, Child-Turcotte-Pugh score between 5 and 8 points and measurable disease per RECIST. Implanted electronic devices in the torso was exclusionary. Standard sorafenib treatment was administered 400 mg (2 x 200 mg tablets). TTFields (150 kHz) were delivered for 18 hours/day until local disease progression (RECIST). Clinical follow up was performed q4w, with CT/MRI scan q12w. Primary endpoint was overall response rate (ORR); secondary: in-field control rate, 12-month progression-free survival rate (PFS12), 1-year OS rate and incidence and severity of adverse events (AE). A sample size of 25 patients would achieve 77% power at 0.05 one-sided alpha to detect overall radiological response rate of 20% in TTFields-treated patients. Conclusions The final safety and efficacy results of the HEPANOVA trial are currently under final analyses. Our hypothesis is that treatment with TTFields as a novel modality for HCC will be efficacious and safe in treatment of advanced HCC. Clinical trial identification NCT03606590. Legal entity responsible for the study Novocure. Funding Novocure. Disclosure All authors have declared no conflicts of interest.