Savolitinib versus sunitinib in patients with MET-driven, unresectable and locally advanced or metastatic papillary renal cell carcinoma: SAVOIR, a randomised, phase III trial

Abstract

Background: Papillary renal cell carcinoma (PRCC) is the most common of the nonclear cell renal cell carcinomas (RCCs), accounting for 10-15% of RCCs. However, there are no therapies approved specifically for patients with PRCC, who currently receive treatments approved for clear cell RCC, such as sunitinib. PRCC is often METdriven (defined as MET kinase domain mutations, MET amplification, chromosome 7 gain and/or HGF amplification). Savolitinib (AZD6094, HMPL-504, volitinib) is a highly selective MET tyrosine kinase inhibitor which demonstrated anti-tumour activity for patients with MET-driven PRCC in a phase II trial. Trial design: SAVOIR (NCT03091192) is a global, phase III, open-label, randomised, controlled trial evaluating the efficacy and safety of savolitinib, compared with sunitinib, in patients with MET-driven, unresectable, locally advanced or metastatic PRCC. Approximately 180 patients will be randomised at~50-75 sites across 5-10 countries. Eligible patients (aged>=18 with MET-driven PRCC confirmed by a novel, sponsor designated, validated, targeted next-generation sequencing assay; a Karnofsky performance status >=80; and measurable disease at baseline) will be randomised in a 1:1 ratio to receive either continuous savolitinib 600 mg (400 mg if<50 kg) orally, once daily (QD), or sunitinib 50 mg orally QD (4 weeks on/2 weeks off). The primary objective is to determine the efficacy of savolitinib compared with sunitinib in terms of progression free survival (PFS). Tumour assessments (RECIST 1.1, confirmed by blinded independent central review [BICR]) will be performed at screening and the end of every 6-week cycle until 12 months, and every 12 weeks thereafter until disease progression. Secondary endpoints include overall survival, objective response rate, duration of response, best percentage change in tumour size, disease control rate at 6 and 12 months, safety and tolerability, and biomarkers. The impact of savolitinib compared with sunitinib on disease symptoms and quality of life, along with the pharmacokinetics of savolitinib will also be assessed.