CALYPSO: Final Results of Savolitinib and Durvalumab Combination in Metastatic Papillary Renal Cancer
Mené sur 41 patients atteints d'un cancer rénal papillaire de stade métastatique (durée médiane de suivi : 41 mois), cet essai de phase II évalue l'efficacité, en fonction de la présence de mutations MET et du point de vue du taux de réponse objective, de la survie sans progression et de la survie globale, et la toxicité d'un traitement combinant savolitinib et durvalumab
Purpose: 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.
Methods: 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.
Results: 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).
Conclusion: 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 , résumé, 2026