Metastatic papillary renal cancer (PRC) has poor outcomes, and new treatments are required. There is a strong rationale for investigating mesenchymal epithelial transition receptor (MET) and programmed cell death ligand-1 (PD-L1) inhibition in this disease. In this study, the combination of savolitinib (MET inhibitor) and durvalumab (PD-L1 inhibitor) is investigated.
This single-arm phase II trial explored durvalumab (1,500 mg once every four weeks) and savolitinib (600 mg once daily; ClinicalTrials.gov identifier: NCT02819596). Treatment-naïve or previously treated patients with metastatic PRC were included. A confirmed response rate (cRR) of > 50% was the primary end point. Progression-free survival, tolerability, and overall survival were secondary end points. Biomarkers were explored from archived tissue (MET-driven status).
Forty-one patients treated with advanced PRC were enrolled into this study and received at least one dose of study treatment. The majority of patients had Heng intermediate risk score (n = 26 [63%]). The cRR was 29% (n = 12; 95% CI, 16 to 46), and the trial therefore missed the primary end point. The cRR increased to 53% (95% CI, 28 to 77) in MET-driven patients (n/N = 9/27) and was 33% (95% CI, 17 to 54) in PD-L1-positive tumors (n/N = 9/27). The median progression-free survival was 4.9 months (95% CI, 2.5 to 10.0) in the treated population and 12.0 months (95% CI, 2.9 to 19.4) in MET-driven patients. The median overall survival was 14.1 months (95% CI, 7.3 to 30.7) in the treated population and 27.4 months (95% CI, 9.3 to not reached [NR]) in MET-driven patients. Grade 3 and above treatment related adverse events occurred in 17 (41%) patients. There was 1 grade 5 treatment-related adverse event (cerebral infarction).
The combination of savolitinib and durvalumab was tolerable and associated with high cRRs in the exploratory MET-driven subset.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Feb 21 [Epub ahead of print]
Cristina Suárez, James M G Larkin, Poulam Patel, Begoña P Valderrama, Alejo Rodriguez-Vida, Hilary Glen, Fiona Thistlethwaite, Christy Ralph, Gopalakrishnan Srinivasan, Maria Jose Mendez-Vidal, Ryan Hartmaier, Aleksandra Markovets, Aaron Prendergast, Bernadett Szabados, Kelly Mousa, Thomas Powles
Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain., The Royal Marsden Hospital, London, United Kingdom., Nottingham University Hospital NHS Trust, Nottingham, United Kingdom., Hospital Universitario Virgen del Rocío, Seville, Spain., Hospital del Mar-CIBERONC, IMIM Research Institute, Barcelona, Spain., Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom., The Christie NHS Foundation Trust and University of Manchester, Manchester, United Kingdom., St. James's Institute of Oncology, University of Leeds, Leeds, United Kingdom., Mid Essex Hospital Services NHS Trust, Broomfield, United Kingdom., Reina Sofía University Hospital, Cordoba, Spain., Translational Medicine, Oncology R&D, AstraZeneca, Gaithersburg, MD., Barts ECMC, Barts Cancer Institute, Queen Mary University London, London, United Kingdom.