Savolitinib and Durvalumab in Metastatic Papillary Renal Cancer

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In the phase II CALYPSO study reported in the Journal of Clinical Oncology, Suárez et al found that the combination of the MET inhibitor savolitinib and the PD-L1 inhibitor durvalumab did not reach the confirmed response rate endpoint in patients with metastatic papillary renal cancer but showed greater activity in those with MET-driven disease.

Study Details

In the trial, 41 treatment-naive or previously treated patients from sites in the United Kingdom and Spain received savolitinib at 600 mg once daily and durvalumab at 1,500 mg every 4 weeks until disease progression or unacceptable toxicity. A total of 17 patients had MET-driven tumors and 27 had PD-L1–positive disease. A confirmed response rate of > 50% was the primary endpoint.


Confirmed objective responses (all partial) were observed in 12 (29%, 95% confidence interval [CI] = 16%–46%) of the 41 patients, with the study endpoint not being met. Confirmed response was observed in 9 (53%, 95% CI = 28%–77%) of 17 patients with MET-driven disease and in 9 (33%, 95% CI = 17%–54%) of 27 with PD-L1–positive disease.

Median duration of response was 9.4 months (95% CI = 5.5 months to not reached) among all responders and 11.5 months (95% CI = 3.9 months to not reached) among responders with MET-driven disease. A response was observed in 10 (37%) of 27 treatment-naive patients and in 2 (14%) of 14 previously treated patients.  

Median follow-up was 26.8 months (95% CI = 19.2–34.3 months). Median progression-free survival was 4.9 months (95% CI = 2.5–10.0 months) among all patients and 12.0 months (95% CI = 2.9–19.4 months) among patients with MET-driven disease. Median overall survival was 14.1 months (95% CI = 7.3–30.7 months) among all patients and 27.4 months (95% CI = 9.3 months to not reached) among those with MET-driven disease.

Adverse Events

Grade ≥ 3 treatment-related adverse events occurred in 41% of patients. The most commonly reported events were edema (10%), transaminitis (9%), and dyspnea (5%); one grade 5 treatment-related adverse event was observed (cerebral infarction). Serious adverse events occurred in 39% of patients, most commonly infection (17%).

The investigators concluded, “The combination of savolitinib and durvalumab was tolerable and associated with high confirmed response rates in the exploratory MET-driven subset.”

Thomas Powles, MD, PhD, of Queen Mary University of London, Barts Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by AstraZeneca UK Ltd. For full disclosures of the study authors, visit