Trial Design: International, multicentre, open label phase Ib/IIa study of durvalumab alone, savolitinib alone, and durvalumab in combination with savolitinib or tremelimumab in patients with metastatic renal cell cancer. CALYPSO will be carried out in two phases, a dose finding phase and a dose expansion/randomised phase.
Patients with metastatic renal cell cancer, either papillary or clear cell, (irrespective of PD-L1 and MET alteration status) were enrolled in the dose finding phase. This component allowed de-escalation of both savolitinib and durvalumab doses with intensive safety monitoring to ensure patient safety. This part of the study is now closed.
The expansion phase aims to evaluate the two cohort populations separately (irrespective of PD-L1 and MET alteration status). Patients with metastatic clear cell renal cancer or sarcomatoid renal cancer will be randomised (1:1:1:1) to receive either savolitinib alone or durvalumab alone or savolitinib plus durvalumab or tremelimumab plus durvalumab. In addition, metastatic papillary cell renal cancer will receive the combination of savolitinib and durvalumab. In both disease cohorts patients will receive treatment until progression at which point they will enter a survival follow up.
Retrospective exploratory biomarker analysis results will be compared with responses to savolitinib, tremelimumab and durvalumab.
Chief Investigator: Prof T. Powles
Trial contact: email@example.com
Clinical Trials.gov: NCT02819596
Sponsor: Queen Mary University of London
Participating countries: UK, Spain
Source of funding: Astra Zeneca UK Limited (funding and study drug)
Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer. Cristina Suarez Rodriguez, James Larkin, Poulam M. Patel et al. J Clin Oncol 39, 2021 (suppl 15; abstr 4511).
Overall survival results for durvalumab and savolitinib in metastatic papillary renal cancer. Cristina Suarez Rodriguez, James M. G. Larkin, Poulam Patel, et al. Journal of Clinical Oncology 2020 38:6_suppl, 619-619.
A phase II study investigating the safety and efficacy of savolitinib and durvalumab in metastatic papillary renal cancer (CALYPSO). Thomas Powles, James M. G. Larkin, Poulam Patel et al. Journal of Clinical Oncology (2019) 37:7_suppl, 545-545.
Cancer Research UK website A trial looking at MEDI4736, savolitinib and tremelimumab for advanced kidney cancer (CALYPSO)