CALYPSO: Final Results of Savolitinib and Durvalumab Combination in Metastatic Papillary Renal Cancer.

Abstract

The CALYPSO study demonstrated activity of savolitinib and durvalumab in <i>MET</i>-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 <i>MET</i>/PD-L1 or <i>MET</i>/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 <i>MET</i>-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 <i>MET</i>-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 <i>v</i> 33.3 months), while ctDNA clearance and mean variant allele frequency reduction correlated with improved OS (median 31.3 <i>v</i> 7.2 and 31.3 <i>v</i> 15.5 months, respectively). Savolitinib plus durvalumab shows OS in <i>MET</i>-driven PRC, supporting the ongoing SAMETA RIII trial (ClinicalTrials.gov identifier: NCT05043090). ctDNA may be a useful predictive biomarker.