ASCO 2017: A phase III trial to compare efficacy and safety of lenvatinib in combination with everolimus or pembrolizumab vs sunitinib alone in first-line treatment of patients (Pts) with metastatic renal cell carcinoma (RCC)

Chicago, IL ( As we continue to explore combination therapy for first-line treatment of metastatic renal cell carcinoma (RCC), there are a number of ongoing phase III studies in this arena. Today at the 2017 ASCO annual meeting, Dr. Motzer and colleagues presented their study design of their trial of lenvatinib in combination with everolimus or pembrolizumab vs sunitinib. Lenvatinib is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptor 1–3, fibroblast growth factor receptor 1–4, platelet-derived growth factor receptor alpha, and RET and KIT. Based on a phase 2 study, lenvatinib was approved in combination with everolimus for treatment of metastatic RCC following one prior VEGF-targeted therapy [1]. Also, a phase 1b/2 study of lenvatinib in combination with pembrolizumab in patients with metastatic RCC is also underway.

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
Twitter: @zklaassen_md

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.