ASCO 2017: Avelumab plus axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma: Phase 3 study (JAVELIN Renal 101)

Chicago, IL ( Over the last several years, we have seen a number of different combination regimens proposed in the first-line for advanced renal cell carcinoma (RCC). Dr. Choueiri and colleagues presented their study design for the phase III JAVELIN Renal 101 study comparing avelumab + axitinib vs sunitinib as first-line treated for advanced RCC at today’s 2017 ASCO annual meeting. Avelumab is a fully human IgG1 anti–PD-L1 antibody with clinical activity in advanced RCC and other tumor types. Axitinib is an anti-VEGF receptor tyrosine kinase inhibitor approved for second-line treatment of advanced RCC [1] that has also shown clinical activity as a first-line therapy [2]. In an ongoing phase 1b study in treatment-naïve patients with advanced RCC, avelumab + axitinib administered at standard monotherapy doses showed a tolerable safety profile and encouraging antitumor activity [3].

The primary objective of JAVELIN Renal 101 is to demonstrate superiority of avelumab + axitinib vs sunitinib in prolonging progression-free survival (PFS) in the first-line treatment of patients with advanced RCC. Eligibility criteria include: (i) advanced RCC with a clear cell component, (ii) ECOG performance status ≤1, (iii) no prior systemic therapy for advanced disease, and (iv) measurable disease per RECIST v1.1. Approximately 583 patients will be randomized 1:1 and stratified based on ECOG performance status (0 vs 1) and region (US vs Canada/Europe vs rest of the world). Patients will receive either avelumab 10 mg/kg IV every 2 weeks + axitinib 5 mg orally BID continuously (each cycle, 6 weeks) or sunitinib 50 mg orally once daily for 4 weeks followed by 2 weeks off. Patients may continue treatment beyond progression (RECIST v1.1) if investigator-assessed clinical benefit is achieved and treatment is well tolerated. Secondary objectives include (i) overall survival, (ii) objective response, (iii) disease control, (iv) duration of response, and (v) time to response.

The trial began enrolling in March 2016, is currently active at 103 sites across 12 countries in North America, Europe and Asia-Pacific, and as of February 2017, more than 40% of patients have been enrolled.
Clinical trial: NCT02684006

Presented By: Toni K. Choueiri, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA, USA

Co-Authors: Brian I. Rini, James M. G. Larkin, Georg A. Bjarnason, Gwenaelle Gravis, Howard Gurney, Jae-Lyun Lee, Daniel Keizman, John B. A. G. Haanen, Yoshihiko Tomita, Hirotsugu Uemura, Laurence Albiges, Manuela Schmidinger, Michael B. Atkins, Mariangela Mariani, Michael Shnaidman, Alessandra di Pietro, Robert J. Motzer

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. Rini BI, Escudier B, Tomczak, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): A randomized phase III trial. Lancet 2011 Dec 3;378(9807):1931-1939.
2. Hutson TE, Lesovoy V, Al-Shukri S, et al. Axitinib versus sorafenib as first line therapy in patients with metastatic renal-cell carcinoma: A randomized open-label phase III trial. Lancet Oncol 2013 Dec;14(13):1287-1294.
3. Larkin J, Rini BI, Nathan P, et al. Phase Ib dose-finding study of avelumab (anti-PD-L1) + axitinib in treatment-naïve patients with advanced renal cell carcinoma. Ann Oncol 2016;27(suppl_6):775PD.