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

Clinical Snapshot

Key Findings

• P Value: Not reported for primary endpoints

• Effect Size: Median OS 18.3 months (ITT) vs 27.4 months (MET-driven)

• Primary Outcome: Overall response rate 34% (95% CI: 20.0-51.0) in ITT population, 53% (95% CI: 28.0-77.0) in MET-driven patients

• Nnt Or Sensitivity: ctDNA positivity associated with shorter OS (7.3 vs 33.3 months); ctDNA clearance correlated with improved OS (31.3 vs 7.2 months)

• Confidence Interval: OS ITT: 95% CI 7.3-30.7 months; MET-driven: 95% CI 9.3-37.4 months

Clinical Application

Requires access to MET inhibitor savolitinib and PD-L1 inhibitor durvalumab, plus molecular testing capabilities for patient selection Durvalumab available on PBS for certain indications; savolitinib not currently PBS-listed. Would require TGA approval and PBS consideration. Molecular testing infrastructure available through major cancer centres Patients with metastatic papillary renal cancer, particularly those with MET-driven tumours identified through molecular testing

Abstract

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.

References

1. 1.Jackson-Spence, F., Larkin, J., Patel, P., Valderrama, B. P., Rodriguez-Vida, A., Glen, H., Thistlethwaite, F. C., Ralph, C., Srinivasan, G., Mendez-Vidal, M. J., Childress, M., Li, W., Boyle, P., Gascó, A., Markovets, A., Hartmaier, R., Ackerman, C., Szabados, B. E., Priyadarshini, G., Jamal, F., Powles, T., & Suárez, C. (2026). CALYPSO: Final results of savolitinib and durvalumab combination in metastatic papillary renal cancer. Journal of Clinical Oncology. https://doi.org/10.1200/JCO-25-01840