Table 2.
Novel targeted multikinase inhibitors currently being investigated in clinical trials for hepatocellular carcinoma
| Agent | Target | Trial | Efficacy | Reference |
|---|---|---|---|---|
| Brivanib | FGFR 1–3 PDGFR VEGFR 1–3 |
Phase III, BRISK-FL. Randomized, double-blind, multi-center Phase III study of brivanib versus sorafenib as first-line treatment in patients with advanced hepatocellular carcinoma (NCT00858871) | Median OS was 9.9 months for sorafenib versus 9.5 months for brivanib | 130 |
| Phase III, BRISK PS. A randomized, double-blind, multi-center Phase III study of brivanib plus best supportive care (BSC) versus placebo plus BSC in subjects with advanced hepatocellular carcinoma (HCC) who have failed or are intolerant to sorafenib. (NCT00825955) | Median OS was 9.4 months for brivanib versus 8.2 months for placebo | 139 | ||
| Phase III, BRISK APS. A randomized, double-blind, multi-center Phase III study of brivanib plus best supportive care (BSC) versus placebo plus BSC in Asian subjects with advanced hepatocellular carcinoma (HCC) who have failed or are intolerant to sorafenib (NCT01108705) | Ongoing | 133 | ||
| Phase III, BRISK-TA. A randomized, double-blind, multicenter Phase III study of brivanib versus placebo as adjuvant therapy to trans-arterial chemo-embolization (TACE) in patients with unresectable hepatocellular carcinoma (NCT00908752) | Ongoing | 133 | ||
| TSU-68 (orantinib) |
FGFR PDGFR VEGFR |
Phase III, ORIENTAL trial. A randomized, double-blind, placebo-controlled Phase III trial of TSU-68 in combination with transcatheter arterial chemoembolization in patients with unresectable hepatocellular carcinoma (NCT01465464) | Ongoing | 131 |
| Dovitinib (TKI-258) |
FGFR VEGFR PDGFR |
Phase II. An open-label, randomized, multi-center, Phase II study to compare the safety and efficacy of TKI258 versus sorafenib as first-line treatment in adult patients with advanced hepatocellular carcinoma (NCT01232296) | Ongoing | 133 |
| Lenvatinib (E7080) |
FGFR VEGFR |
Phase I/II. Phase I/II study of E7080 in patients with advanced hepatocellular carcinoma (HCC) (NCT00946153) | Ongoing | 134 |
| PDGFR RER KIT |
Phase III. A multicenter, open-label, Phase III trial to compare the efficacy and safety of lenvatinib (E7080) versus sorafenib in first-line treatment of subjects with unresectable hepatocellular carcinoma (NCT01761266) | Recruiting | 133 | |
| Nintedaninb (BIBF 1120) |
FGFR PDGFR VEGFR |
Phase I. An open label, dose escalation Phase I study to evaluate the safety and tolerability of continuous twice-daily oral treatment of nintedanib in Japanese patients with hepatocellular carcinoma (NCT01594125) | Recruiting | 133 |