Phase II Study Investigating the Safety and Efficacy of Savolitinib and Durvalumab in Metastatic Papillary Renal Cancer (CALYPSO).

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.

• Authors: Cristina Suárez, James M G Larkin, Poulam Patel, Begoña P Valderrama, Alejo Rodriguez-Vida, Hilary Glen, Fiona Thistlethwaite, Christy Ralph, Gopalakrishnan Srinivasan, Maria Jose Mendez-Vidal, Ryan Hartmaier, Aleksandra Markovets, Aaron Prendergast, Bernadett Szabados, Kelly Mousa, Thomas Powles
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 41 Issue 14 Pg. 2493-2502 (05 10 2023) ISSN: 1527-7755 [Electronic] United States
• PMID: 36809050 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• durvalumab
• 1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine
• thiacloprid
• B7-H1 Antigen

Topics

• Humans
• B7-H1 Antigen
• Kidney Neoplasms (drug therapy)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)