Adding MET, CTLA-4 Inhibitor Did Not Improve Efficacy of Durvalumab in Advanced ccRCC

The use of the MET inhibitor savolitinib alone, or in combination with PD-L1 inhibitor durvalumab in patients with previously treated advanced clear cell renal cell carcinoma did not demonstrate efficacy, according to data from CALYPSO (Abstract LBA4503).

The study also showed no superior efficacy with the addition of CTLA-4 inhibitor tremelimumab to durvalumab in this disease setting. These findings were presented by Thomas Powles, MD, PhD, FCRP, of Barts ECMC, Barts Cancers Institute, Queen Mary University of London, at the 2022 ASCO Annual Meeting.

These data were from an open-label, randomized phase-2 study assessing new treatment combinations including MET inhibition and CTLA-4 inhibition in patients with advanced clear cell RCC. The study included 139 patients with previous VEGF targeted therapy but without prior MET or immune checkpoint inhibition.

Patients were randomly assigned to durvalumab alone (39 patients), savolitinib alone (22 patients), savolitinib plus durvalumab (DS; 39 patients) or tremelimumab plus durvalumab (DT; 39 patients). The savolitinib arm was closed early due to lack of efficacy.

The primary endpoint was confirmed response rate. A response rate of 50% was required for further exploration.

The abstract included outcomes from a pre-planned 12-month interim analysis. At that time, none of the complete response rates met the primary objective. Complete response rates were 10% for durvalumab, 5% for savolitinib, 28% for DT, and 13% for DS.

Looking at subgroups, the complete response rates in 17 patients with MET-driven disease were 0% for durvalumab alone, 0% for savolitinib alone, 50% for DT, and 17% for DS. In patients with PD-L1 positive disease, the complete response rates were 14% for DT and 22% for durvalumab alone.

The 12-month progression-free survival rates were 26% for durvalumab, 21% for savolitinib, 33% for DT, and 17% for DS.

Median overall survival was 26.1 months for durvalumab, 23.1 months for savolitinib, 21.9 months for DT, and 16.1 months for DS.

One treatment-related death occurred in the DR arm.