Japanese-based pharmaceutical company Eisai has commenced its Phase III CLEAR Study of Lenvima (lenvatinib) combined with Keytruda (pembrolizumab) and Lenvima with everolimus against sunitinib to treat advanced renal cell carcinoma (RCC) in the first-line setting.
Lenvima is a receptor tyrosine kinase (RTK) inhibitor designed to prevent kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1-3.
Additionally, it can also inhibit other RTKs believed to trigger pathogenic angiogenesis, tumour growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet-derived growth factor receptor alpha (PDGFRα), KIT and RET.
Merck’s humanised monoclonal antibody Keytruda boosts the body's immunity system to detect and fight tumour cells.
It resists PD-1 from interacting with its ligands, PD-L1 and PD-L2, subsequently activating T-lymphocytes, which may affect both tumour and healthy cells.
Novartis’ Everolimus is approved in the US as Afinitor and is indicated to treat locally advanced, metastatic or unresectable progressive nonfunctional neuroendocrine tumours (NET) of pancreatic origin.
The Phase III Comparison of the efficacy and safety of lenvatinib in combination with Everolimus or pembrolizumab versus sunitinib alone in first-line treatment of subjects with Advanced Renal cell carcinoma (CLEAR) study has been designed as a multicentre, randomised, open-label trial.
It intends to compare the efficacy and safety of lenvatinib / everolimus and lenvatinib / pembrolizumab against sunitinib alone in first-line treatment in patients with advanced renal cell carcinoma.
The study is primarily focused on achieving a progression-free survival by the medical combination.
A non-clinical research of the lenvatinib and everolimus combination suggested synergistic enhancement of antiangiogenic activity and an anti-tumour effect.
Additionally, non-clinical research of the lenvatinib and anti-PD-1 antibody combination demonstrated its mechanism of action in enhancing the anti-tumour activity of the anti-PD-1 antibody by reducing immunosuppressive cells.