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.
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.
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 ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.