Eligible patients for this study include those (i) aged ≥ 18 years with confirmed advanced RCC diagnosis, (ii) ≥ 1 measurable lesion per RECIST v1.1, (iii) Karnofsky Performance Status ≥ 70, (iv) controlled blood pressure, and (v) adequate blood coagulation, renal, hepatic, and bone marrow function. Patients will be randomized 1:1:1 to receive lenvatinib 18 mg/day + everolimus 5 mg/day, lenvatinib 20 mg/day + pembrolizumab 200 mg every 3 weeks, or sunitinib 50 mg/day (on a schedule of 4 weeks on treatment followed by 2 weeks off) until disease progression, unacceptable toxicity, withdrawal of consent, or study end. The primary endpoint is to show superiority of lenvatinib + everolimus or lenvatinib + pembrolizumab over single-agent sunitinib as first-line treatment for advanced RCC in improving progression-free survival (PFS). Enrollment of 735 patients is planned to achieve 90% power at two-sided α = 0.05 to detect a difference in ≥ 1 of the primary comparisons. Secondary endpoints include (i) comparison of objective response rate, (ii) overall survival, (iii) PFS on next-line therapy, (iv) health-related quality of life, and (v) safety/tolerability. Exploratory endpoints include (i) PFS in the lenvatinib + pembrolizumab arm using immune-related RECIST, (ii) comparison of duration of response, (iii) disease control rate, and (iv) clinical benefit rate in patients treated with lenvatinib + everolimus or lenvatinib + pembrolizumab vs sunitinib, and (v) analysis of the relationship between blood biomarkers and outcome.
Clinical trial: NCT02811861
Presented By: Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Co-Authors: Viktor Grünwald, Thomas E. Hutson, Camillo Porta, Thomas Powles, Masatoshi Eto, Corina E Dutcus, Mahadi Ali Baig, Lea Dutta, Di Li, Toni K. Choueiri
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA
1. Motzer RJ, Hutson TE, Glen H, et al Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: A randomized, phase 2, open-label, multicenter trial. Lancet Oncology 2015 Nov;16(15):1473-1482.