Entry Detail
| General information | |
| Database: | DB00139 |
| Objective: | a phase 1/2 study of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE2, and VEGFR as firstline therapy in Asian advancedhepatocellular carcinoma patients. |
| Authors: | Thomas Cheung Yau, et al |
| Title: | a phase 1/2 study of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE2, and VEGFR as firstline therapy in Asian advancedhepatocellular carcinoma patients. |
| Journal: | J Clin Oncol |
| Year: | 2012 ASCO Annual Meeting |
| PMID: | J Clin Oncol 30, 2012 (suppl; abstr 4108) |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | foretinib |
| Target: | Vascular endothelial growth factor receptor 2 Hepatocyte growth factor receptor |
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I/II trial (METIII645) |
| Key Patients Feature: | Asian patients with measurable, unresectable/metastatic hepatocellular carcinoma, no prior sorafenib or other multikinase inhibitors, ECOG PS 01, adequate organ function and ChildPugh grade A were recruited. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | the phase I was a standard 3+3 dose escalation design with a phase II cohort expansion. |
| Primary End Point: | safety and tolerability at the maximum tolerated dose (MTD) |
| Secondary End Point: | antitumor activity (objective response rate [ORR], disease stabilization rate [DSR; confirmed CR/PR or SD for at least 12 weeks], and time to progression [TTP] evaluated by central review according to modified RECIST), and overall survival (OS) at the MTD, plus pharmacokinetics (PK). |
| Patients Number: | 45 |
| Trial Results | |
| DLT_MTD: | Two doselimiting toxicities (DLT) (renal failure, proteinuria) were observed at 45 mg once daily (QD) but no DLTs were observed at 30 mg QD. Thus, the MTD was determined to be 30 mg QD. |
| Objective Response Rate: | No dose reductions were reported. Thirtyeight patients were evaluable for efficacy. The ORR was 24% (95% CI 1140), DSR 79% (95% CI; 6390), |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | median TTP was 4.2 months (95% CI 2.77.5). |
| Median OS A vs. C: | Mature OS data will be presented. |
| Adverse Event(agent arm): | The most common AEs, independent of causality, were hypertension (36%), decreased appetite (23%), and pyrexia (21%). The most common SAEs were hepatic encephalopathy (10%) and ascites (8%). Two patients discontinued foretinib due to AEs. |
| Conclusions: | Foretinib has an acceptable safety, tolerability, and PK profile in an Asian hepatocellular carcinoma population. It has demonstrated promising antitumor activity that warrants further testing in a randomized setting. |