The combination of savolitinib and durvalumab has demonstrated compelling efficacy in patients with MET-driven advanced papillary renal cancer, according to final overall survival data from the CALYPSO trial presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.
Superior Outcomes in MET-Driven Population
The study revealed particularly strong results in the MET-driven subset of patients, with a confirmed response rate of 53% compared to 32% in the intention-to-treat population. Progression-free survival in the MET-driven group reached 13 months, substantially longer than the 6.5 months observed in the overall cohort.
Most notably, median overall survival in the MET-driven subset extended to 27.4 months, representing a significant improvement over the 18-month survival seen in the intention-to-treat population.
Breakthrough Findings in ctDNA Analysis
Dr. Francesca Jackson-Spence, clinical research fellow at Barts Cancer Institute, presented intriguing data on circulating tumor DNA (ctDNA) analysis. The study found that 48% of patients were ctDNA-positive at baseline, with this status potentially serving as a predictive biomarker for treatment response.
Among patients who responded to the savolitinib-durvalumab combination, only 22% were ctDNA-positive at baseline, compared to 89% of non-responders. The impact on survival was particularly striking, with ctDNA-negative patients achieving a median overall survival of 33 months, while ctDNA-positive patients had a median survival of just 7 months.
Looking to Future Validation
While the study also examined ctDNA clearance and its association with improved survival, the small sample size - with only two patients achieving clearance - necessitates further investigation. Dr. Jackson-Spence emphasized that these findings, while promising, await validation in the ongoing randomized phase 3 SAMETA study.
The CALYPSO trial results suggest that the combination therapy could represent a significant advancement in the treatment of MET-driven papillary renal cancer, particularly for patients who are ctDNA-negative at baseline.
