The CALYPSO study demonstrated activity of savolitinib and durvalumab in MET-driven papillary renal cancer (PRC). We report final efficacy outcomes and exploratory circulating tumor DNA (ctDNA) biomarker analysis.
This single-arm phase II study evaluated savolitinib and durvalumab in treatment-naïve or pretreated PRC. End points included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). FoundationOne CDx assessed DNA alterations and MET/PD-L1 or MET/tumor mutational burden (TMB) copositivity. ctDNA collected at baseline and on treatment was correlated with outcomes.
At 41-months median follow-up, ORR was 34% (95% CI, 20.0 to 51.0) in the intention-to-treat (ITT) population (N = 41) and 53% (95% CI, 28.0 to 77.0) in MET-driven patients (n = 17). Median PFS was 6.5 (95% CI, 2.7 to 12.0) versus 13.9 months (95% CI, 2.9 to 23.8), and OS was 18.3 (95% CI, 7.3 to 30.7) versus 27.4 months (95% CI, 9.3 to 37.4), in the ITT population and the MET-driven population, respectively. PD-L1 (66% positive) and TMB (median 2.5 mut/Mb) status did not correlate with response. Baseline ctDNA positivity (10/21) correlated with shorter OS (median 7.3 v 33.3 months), while ctDNA clearance and mean variant allele frequency reduction correlated with improved OS (median 31.3 v 7.2 and 31.3 v 15.5 months, respectively).
Savolitinib plus durvalumab shows OS in MET-driven PRC, supporting the ongoing SAMETA RIII trial (ClinicalTrials.gov identifier: NCT05043090). ctDNA may be a useful predictive biomarker.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2026 Mar 20 [Epub ahead of print]
Francesca Jackson-Spence, James Larkin, Poulam Patel, Begoña P Valderrama, Alejo Rodriguez-Vida, Hilary Glen, Fiona C Thistlethwaite, Christy Ralph, Gopalakrishnan Srinivasan, Maria Jose Mendez-Vidal, Merrida Childress, Wenshu Li, Patrick Boyle, Amaya Gascó, Aleksandra Markovets, Ryan Hartmaier, Charlotte Ackerman, Bernadett E Szabados, Garima Priyadarshini, Fahmida Jamal, Thomas Powles, Cristina Suárez
Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., 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, Hospital del Mar 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., Foundation Medicine Inc, Boston, MA., Oncology Data Science and AI, AstraZeneca Oncology R&D, Boston, MA., Translational Medicine, AstraZeneca Oncology R&D, Boston, MA., Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Spain.