Combining a checkpoint inhibitor with an anti-VEGF therapy is a promising treatment strategy for advanced renal cell carcinoma (aRCC). Avelumab* (MSB0010718C) is a fully human IgG1 anti-PD-L1 antibody with clinical activity in aRCC and other tumour types (eg, Apolo et al. ECC-ESMO 2015; Gulley et al. ECC-ESMO 2015). Axitinib is an anti-VEGF receptor tyrosine kinase inhibitor approved for second-line treatment of aRCC (Rini et al. Lancet 2011), which has also shown clinical activity as a first-line (1L) therapy (Hutson et al. Lancet Oncol 2013). An ongoing phase 1b study of avelumab + axitinib, administered at standard doses, showed tolerable safety and encouraging antitumour activity in treatment-naïve pts with aRCC. JAVELIN Renal 101, a randomized, multicenter, phase 3 study (NCT02684006) compares avelumab + axitinib vs sunitinib in treatment-naïve pts with aRCC.
The primary objective is to demonstrate superiority of 1L avelumab + axitinib vs sunitinib monotherapy in prolonging progression-free survival (PFS). Eligibility criteria include: aRCC with a clear cell component, ECOG PS ≤1, no prior systemic therapy for advanced disease, and measurable disease per RECIST v1.1. Approximately 583 pts will be randomized (1:1) and stratified based on ECOG PS (0 vs 1) and region (US vs Canada/Europe vs rest of the world). Pts receive either avelumab 10 mg/kg IV Q2W + axitinib 5 mg orally BID continuously (cycle length 6 weeks) or sunitinib 50 mg orally once daily for 4 weeks followed by 2 weeks off. Treatment is discontinued for unacceptable toxicity or if any criteria for withdrawal are met. Pts may continue treatment beyond progression (RECIST v1.1) if investigator-assessed clinical benefit is achieved and treatment is well tolerated. PFS will be assessed by blinded independent central review. Secondary endpoints include overall survival, PFS by investigator assessment, objective response, duration of response, time to response, safety, tumour biomarker assessments, and patient-reported outcomes. Enrolment in this pivotal phase 3 trial began in March 2016. *Proposed INN.
Clinical trial identification
Legal entity responsible for the study
R.J. Motzer: Consulting or Advisory Role: Pfizer, Novartis, Eisai Inc. Research Funding: Exelixis, BMS, Novartis, Pfizer, Genentech/Roche. T. Choueiri: Consulting or advisory role: Pfizer, Bayer, Novartis, GSK, Merck, BMS, Roche, Eisai, Prometheus Labs Inc, Foundation Medicine Inc., Cerulean. Research funding: Pfizer, Novartis, Merck, Exelixis, Tracon, GSK, BMS, AstraZeneca, Peloton, Roche. L. Albiges: Consulting or Advisory Role: Novartis, Pfizer, Amgen, BMS, Bayer, Sanofi, and Cerulean. Research Funding: Novartis and Pfizer. J.B. Haanen: Consulting/Advisory Role: BMS, MSD, Roche, Pfizer, Novartis, Neon Institution Research Funding: BMS, MDS, GSK. M. Schmidinger: Honoraria for lectures or consultancy from Pfizer, Novartis, Roche, BMS, Exelixis, Astellas Travel grants from Roche and Pfizer M.B. Atkins: Consulting or Advisory Role: Merck, Pfizer, AstraZeneca, BMS, Eisai, Genentech, Novartis, X4, Acceleron, Peloton, and Nektar. M. Mariani, M. Shnaidman: Employee and Stockholder: Pfizer Inc. A. Di Pietro: Employment: Pfizer. B.I. Rini: Consulting or Advisory Role: Roche, BMS, Pfizer, Acceleron, Novartis, GSK. Research Funding: Pfizer, BMS, Acceleron, Immatics, Peloton. Travel, Accommodations, Expenses: Pfizer. All other authors have declared no conflicts of interest.