1717TiP CARE1 pragmatic clinical trial: First line randomised study platform to optimize treatment in patients with metastatic renal cell carcinoma

Abstract

Background: Systemic therapy for renal cell carcinoma (RCC) relies on two classes of agents: vascular endothelial growth factor tyrosine kinase inhibitors (VEGFR TKI) and immune checkpoint inhibitors (ICI) targeting either PD1 or CTLA4. ICI based combination therapy is standard-of-care for clear cell RCC with either ICI-ICI or ICI-VEGFR TKI. However, no head-to-head comparison have been performed between the two approaches and patients are treated based on physician decision without biomarker to guide treatment selection. PDL1 staining may help select patient who derive benefit to upfront ICI-ICI strategy. Trial design: The CARE1 study is a pragmatic phase III international multicenter randomized clinical trial funded by the European Union's Horizon Europe research and innovation program under grant agreement No 101104801, PHRC grant Ndegree K2022-2023 provided by National Cancer Institute in France, Gustave Roussy and CRIS Cancer Foundation Real-Life Trials in Oncology Programme. The main objective of CARE1 is to demonstrate that ICI-ICI improves overall survival over ICI-VEGFR TKI in PDL1 positive patients with metastatic clear-cell renal cell carcinoma in the first line setting, and conversely to demonstrate that ICI-VEGFR TKI improves overall survival over ICI-ICI in PDL1 negative patients. PDL1 positivity is defined locally as >=1% of stained tumor cells. Patients will be randomized 1:1 to receive ICI-ICI or ICI-TKI. Secondary endpoints are progression-free survival (PFS) - PFS will be a co-primary endpoint specifically in the PDL1 negative population -, objective response rate according to RECIST 1.1, duration of treatment, time-to-treatment discontinuation, treatment-free survival, time to subsequent systemic anticancer therapy, quality of life, safety and cost-effectiveness. A comprehensive translational program including tissue and circulating biomarkers is embedded into the CARE1 study. The trial is currently recruiting and 1200 patients will be enrolled across 8 European countries. Clinical trial identification: EUCT 2023-503317-29-00; NCT0636463. Legal entity responsible for the study: Gustave Roussy.