Phase II study investigating the safety and efficacy of savolitinib and durvalumab in metastatic papillary renal cancer (CALYPSO)
Suárez, C. Larkin, J. M. G. Patel, P. Valderrama, B. P. Rodriguez-Vida, A. Glen, H. Thistlethwaite, Fiona C Ralph, C. Srinivasan, G. Mendez-Vidal, M. J.
Suárez, C.
Larkin, J. M. G.
Patel, P.
Valderrama, B. P.
Rodriguez-Vida, A.
Glen, H.
Thistlethwaite, Fiona C
Ralph, C.
Srinivasan, G.
Mendez-Vidal, M. J.
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Abstract
Purpose: Metastatic papillary renal cancer (PRC) has poor outcomes, and new treatments are required. There is a strong rationale for investigating mesenchymal epithelial transition receptor (MET) and programmed cell death ligand-1 (PD-L1) inhibition in this disease. In this study, the combination of savolitinib (MET inhibitor) and durvalumab (PD-L1 inhibitor) is investigated.
Methods: This single-arm phase II trial explored durvalumab (1,500 mg once every four weeks) and savolitinib (600 mg once daily; ClinicalTrials.gov identifier: NCT02819596). Treatment-naïve or previously treated patients with metastatic PRC were included. A confirmed response rate (cRR) of > 50% was the primary end point. Progression-free survival, tolerability, and overall survival were secondary end points. Biomarkers were explored from archived tissue (MET-driven status).
Results: Forty-one patients treated with advanced PRC were enrolled into this study and received at least one dose of study treatment. The majority of patients had Heng intermediate risk score (n = 26 [63%]). The cRR was 29% (n = 12; 95% CI, 16 to 46), and the trial therefore missed the primary end point. The cRR increased to 53% (95% CI, 28 to 77) in MET-driven patients (n/N = 9/27) and was 33% (95% CI, 17 to 54) in PD-L1-positive tumors (n/N = 9/27). The median progression-free survival was 4.9 months (95% CI, 2.5 to 10.0) in the treated population and 12.0 months (95% CI, 2.9 to 19.4) in MET-driven patients. The median overall survival was 14.1 months (95% CI, 7.3 to 30.7) in the treated population and 27.4 months (95% CI, 9.3 to not reached [NR]) in MET-driven patients. Grade 3 and above treatment related adverse events occurred in 17 (41%) patients. There was 1 grade 5 treatment-related adverse event (cerebral infarction).
Conclusion: The combination of savolitinib and durvalumab was tolerable and associated with high cRRs in the exploratory MET-driven subset.
Description
Date
2023
Publisher
Collections
Keywords
Type
Article
Citation
Suárez C, Larkin JMG, Patel P, Valderrama BP, Rodriguez-Vida A, Glen H, et al. Phase II Study Investigating the Safety and Efficacy of Savolitinib and Durvalumab in Metastatic Papillary Renal Cancer (CALYPSO). Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Feb 21:JCO2201414. PubMed PMID: 36809050. Epub 2023/02/23. eng.