As reported in the Journal of Clinical Oncology by Jackson-Spence et al, final results of the phase II CALYPSO study indicated better overall survival and other outcomes with savolitinib and durvalumab among patients with metastatic papillary renal cancer who have MET-driven disease.
Study Details
In the European multicenter trial, 41 patients (intention-to-treat [ITT] population) received savolitinib at 600 mg once daily for 28 days with durvalumab at 1,500 mg every 4 weeks starting on day 29 until disease progression or unacceptable toxicity. A total of 17 patients had MET-driven disease.
Key Findings
Median follow-up was 41 months. Objective response rates were 34% (95% confidence interval [CI] = 20.0%–51.0%) in the ITT population vs 53% (95% CI = 28.0%–77.0%) in the MET-driven subgroup. Median progression-free survival was 6.5 months (95% CI = 2.7–12.0 months) in the ITT population vs 13.9 months (95% CI = 2.9–23.8 months) in the MET-driven subgroup. Median overall survival was 18.3 months (95% CI = 7.3–30.7 months) in the ITT population vs 27.4 months (95% CI = 9.3–37.4 months) in the MET-driven subgroup.
No correlation with response was observed for PD-L1 status (66% of patients positive) or tumor mutation burden (median = 2.5 mut/Mb) status. Baseline ctDNA positivity, observed in 10 of 21 evaluable patients, was associated with shorter overall survival (median = 7.3 vs 33.3 months); ctDNA clearance (median = 31.3 vs 7.2 months) and reduction in mean variant allele frequency (median = 31.3 vs 15.5 months) were associated with improved overall survival.
The investigators concluded: “Savolitinib plus durvalumab shows [overall survival benefit] in MET-driven [papillary renal cancer], supporting the ongoing [phase III] SAMETA RIII trial (ClinicalTrials.gov identifier: NCT05043090). ctDNA may be a useful predictive biomarker.”
Thomas Powles, MD, MBBS, of Barts Cancer Institute, Queen Mary University of London, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by a research grant funded by AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.
