Exploratory treatment options fail in ccRCC 

Although the 4 tested treatment regimens – durvalumab alone, durvalumab plus tremelimumab or savolitinib, or savolitinib alone – of the phase 2 CALYPSO trial appeared to be safe in patients with previously treated advanced clear cell renal cell carcinoma (ccRCC), the primary efficacy endpoint was not met for any treatment regimen. 

The CALYPSO trial (NCT02819596) randomised 139 patients with vascular endothelial growth factor (VEGF) refractory ccRCC to 1 of 4 treatment arms: PD-L1 inhibitor durvalumab alone (n=39), durvalumab plus the CTLA-4 inhibitor tremelimumab (n=39), durvalumab plus the MET inhibitor savolitinib (n=39), or savolitinib alone (n=19). Prof. Thomas Powles (University of London, UK), who presented the results of the trial, added that the savolitinib monotherapy arm was closed early, because the standard-of-care treatment had changed during the course of the study [1]. The primary efficacy endpoint was a confirmed response rate ≥50%.

Confirmed response rates ranged from 5% in the savolitinib alone arm to 28% in the durvalumab plus tremelimumab arm, with no arm reaching the prespecified confirmed response rate ≥50% (see Figure). Prof. Powles argued that the confirmed response rates in the durvalumab plus tremelimumab arm may seem promising, but that nivolumab alone reached a confirmed response rate of 25% in the CheckMate025 trial (NCT01668784) in previously treated patients with ccRCC [2]. Furthermore, savolitinib-containing regimens did not appear to perform better in patients with MET-driven RCC.

Figure: Confirmed response rates in the CALYPSO trial [1]



R, randomised; cRR, confirmed response rate.

Serious adverse event rates occurred in around 30% of participants in the durvalumab alone and durvalumab plus tremelimumab arms, 49% in the durvalumab plus savolitinib arm, and 16% in the savolitinib monotherapy arm. There was 1 treatment-related death in the durvalumab plus tremelimumab arm and none in the other arms.

1. Powles T, et al. CALYPSO: A three-arm randomised phase II study of Durvalumab alone or with Savolitinib or tremelimumab in previously treated advanced clear cell renal cancer. LBA 4503, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.
2. Motzer RJ, et al. NEJM. 2015;373(19):1803–1813. 

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Posted on 5 August 202222 February 2024