Vorolanib (CM082), everolimus, and the combination in patients with pretreated metastatic renal cell carcinoma (CONCEPT study): A randomized, phase 2/3, double-blind, multi-center trial.

Abstract

TPS4605 Background: VEGF and mTOR pathways play key role in the development of renal cell carcinoma (RCC), the combination of agents targeting both VEGF- and mTOR-mediated pathways have been investigated with distinct results. Vorolanib (CM082) is a potent and selective inhibitor of VEGFR and PDGFR. Previous phase 1 study (NCT02577458) found that the combination of vorolanib 200 mg plus everolimus 5mg was associated with manageable toxicity consistent with individual agents and no new safety signals, antitumor activities was also seen in 35.7% patients with RCC patients who progressed on at least one VEGFR TKI therapy. Based on these findings, we conducted the CONCEPT study, a randomized, phase 2/3, double-bind, multicenter trial to assess vorolanib, everolimus, or their combination as second-line treatment in Chinese patients with metastatic RCC. Methods: Patients with cytologically or histologically confirmed RCC who had disease progression after one prior VEGFR TKI were eligible for participation in the study. They will be randomized by 1:1:1 ratio to receive matching placebo plus vorolanib or everolimus, or the combination. Randomization was stratified according to the MSKCC risk scores. The sample size was specified assuming a hazard ratio (HR) of 0.60, equating to an expected 6.5 months for everolimus and 10.5 months for vorolanib with or without everolimus. To provide 80% power at a two-sided 5% significance level, and an estimated 20% dropout rate, a total of 390 patients are required. This study is registered as NCT03095040. Progression: This study in conducted in 35 centers in China, so far 32 centers have been activated. Recruitment was started since March 10, 2017, and a total of 101 patients were randomized currently. Clinical trial information: NCT03095040.