HEPANOVA Trial Update: Final Patient With HCC Enrolled to Receive TTFields/Sorafenib

July 9, 2020

The last patient with advanced hepatocellular carcinoma was enrolled on the phase 2 HEPANOVA trial, which is investigating the combination of Tumor Treating Fields and sorafenib. The combination showed safety and tolerability for patients in an interim analysis.

The last patient with advanced hepatocellular carcinoma (HCC) was enrolled on the phase 2 HEPANOVA trial (NCT03606590), which is investigating the combination of Tumor Treating Fields (TTFields) and sorafenib (Nexavar). The combination showed safety and tolerability for patients in an interim analysis.1,2

This prospective, single-arm pilot trial demonstrated no serious adverse events (AEs) that were unanticipated at the time of the interim analysis in the first 9 patients. Most of the toxicities were expected and associated with HCC or chemotherapy, and the most common AE at the time of the analysis was TTFields-related dermatitis, which was expected.

For all 9 patients, the total treatment duration of TTFields was 29.1 months. Among these patients, 6 (66.7%) experienced severe grade 3/4 AEs and 3 (33.3%) experienced serious AEs, but none of these events were related to TTFields. The only TTFields-related AE was mild-moderate skin toxicity, which was reported in 7 (78%) of the patients. There was a median treatment duration of 2 months with sorafenib and 3 months with TTFields.

Preclinical studies showed that 150kHz of TTFields reduced HepG2 and Huh7D12 cell counts from 53% to 64% and clonogenic potential of about 70%. In an in vitro study, TTFields combined with sorafenib led to a significant reduction in the number of HepG2 and Huh-7D12 cells (P <.001) compared with TTFields alone and sorafenib alone.3 Another study demonstrated a reduced viability, clonogenicity, and increased apoptosis and autophagy in vitro and a significant reduction in tumor volume in vivo with TTFields at 150kHz plus sorafenib.4

“TTFields therapy has demonstrated efficacy in in vitro and in vivo models of HCC,” Asaf Danziger,chief executive officer, Novocure, said in a statement. “We believe that TTFields’ mechanism of action is broadly applicable to solid tumor cancers. We look forward to seeing results from the HEPANOVA trial and further exploring the potential of TTFields as a treatment for advanced liver cancer.”

Now that the last patient is enrolled in the study as of July 7, the final data collection date is 6 months after. The primary end point is overall response rate and the secondary end points include overall survival rate, progression-free survival rate, and distant metastases free survival rate at 1 year, as well as the in-field control rate.1

The 25 patients are receiving TTFields at 150 kHz concomitant with sorafenib 400 mg twice daily. The sample size of this trial was based on the ability to detect an overall response rate of 20% in patients given TTFields versus the 4.5% overall response rate calculated from historical controls.

All of the patients had advanced HCC and were ineligible for surgical resection or local treatments. The median age was 70 years old in the interim analysis and all the patients were male. Three patients had an ECOG performance score of 0. There was a median time from diagnosis of 9 months (range, 0-56 months) and the median number of prior treatments was 2 (range, 0-6 treatments). There were 5 patients with Barcelona Clinic Liver Cancer stage B disease.2

References:

1. Novocure enrolls last patient in HEPANOVA trial testing tumor treating fields in combination with sorafenib in advanced liver cancer. News release. Novocure. Published July 7, 2020. Accessed July 9, 2020. https://bit.ly/3f9Xenc

2. Gkika E, Brunner T, Thimme R, Grosu A-L. CT186 - HEPANOVA: Interim safety analysis from a phase 2 study of Tumor Treating Fields (TTFields, 150 kHz) concomitant with sorafenib in advanced hepatocellular carcinoma (HCC) [Abstract]. In: Proceedings of the 111th Annual Meeting of the American Association for Cancer Research; 2020 June 22-24. Philadelphia (PA): AACR; 2020. Abstract nr CT186.

3. Gotlib K, Zeevi E, Schniederman RS, et al. The combined treatment of 150 kHz Tumor Treating Fields (TTFields) and sorafenib inhibits hepatocellular carcinoma in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res. 2018;78(13 Suppl):Abstract nr 1865.

4. Davidi S, Tempel-Brami C, Munster M, et al. In vitro and in vivo efficacy and safety of tumor treating fields (TTFields) and sorafenib combination in hepatocellular carcinoma.J Clin Oncol. 2020;38(suppl 4):551. doi:10.1200/JCO.2020.38.4_suppl.551