OA11.03 A Randomized, Multi-Center, Double-Blind Phase II Study of Fruquintinib in Patients with Advanced Non-Small Cell Lung Cancer

Abstract

Targeting the tumor microenvironment, such as tumor angiogenesis, has led to the successful development and approval of a number of targeted therapies thereby changing the standard of care for many types of cancer. However, treatment options are limited in third-line non-small cell lung cancer (NSCLC) patients. Fruquintinib is a potent and highly selective oral kinase inhibitor targeting vascular endothelial growth factor receptors and is currently in late stage development for multiple cancers. This Phase II study was designed to evaluate the efficacy and safety of fruquintinib in third-line NSCLC patients (NCT02590965). A total of 91 patients were randomized to receive best supportive care (BSC) plus fruquintinib or BSC plus placebo in a 2:1 ratio from 12 Chinese clinical centers. Fruquintinib initial dose was 5 mg once daily and treatment was given in every 4-week cycle (3 weeks treatment followed by 1 week off). The primary objective was to compare progression free survival (PFS) between the two treatment groups. Secondary efficacy parameters included objective response rate (ORR), disease control rate (DCR), overall survival (OS). Tumor response was assessed per RECIST 1.1. As of August 7, 2015, median PFS was 3.8 months for the fruquintinib group comparing with 1.2 months for the placebo group (hazard ratio=0.27, p<0.001). The ORR was 16.4% for the fruquintinib group comparing with 0% for the placebo group (p=0.02). The DCR of the fruquintinib group was significantly higher than that of the placebo group with a difference of 53.8% (36.3, 71.4; 95% CI, p<0.001). OS was not mature and initial analysis revealed 3- and 6-month OS rates of 90.2% and 68.3% for the fruquintinib group, and 73.3% and 58.2% for the placebo group, respectively. Adverse event was reported in 68.9% and 60.0% patients in fruquintinib and placebo group, respectively. The incidence of serious adverse events was 3.3% in the fruquintinib group and 6.7% in the placebo group. Fruquintinib in third-line NSCLC met the primary efficacy endpoint of PFS and demonstrated superiority in the secondary endpoints of ORR and DCR as compared with placebo. OS has yet to mature. Fruquintinib was generally well tolerated and safety profile consistent with previously reported. These results support further development of fruquintinib in third-line NSCLC patients. A randomized, double-blind, multi-center Phase III registration study was initiated in December 2015 (NCT02691299). Clinical trial information: NCT02590965.