A phase II study bolstering outcomes by optimizing immunotherapy strategies with evolocumab and nivolumab in patients with metastatic renal cell carcinoma (BOOST-RCC).

TPS581 Background: Metastatic clear cell renal cell carcinoma (mccRCC) progressing on prior immune checkpoint inhibitors (ICIs) poses significant challenges, with less effective treatment options in refractory disease. More therapies to overcome ICI resistance are needed. Pro-protein convertase subtilisin/kexin type 9 (PCSK9) directs MHC-I molecules to the lysozyme, and inhibition of PCSK9 improves MHC-I expression and tumor antigen presentation. Evolocumab is a PCSK9 inhibitor shown in preclinical studies to improve tumor antigen expression, intratumoral CD8 T-cell infiltration and activation, and tumor control. We launched BOOST-RCC, a phase 2 trial with safety lead in to give combination evolocumab and nivolumab in mccRCC refractory to ICIs. Methods: BOOST-RCC is an investigator-initiated, phase 2, multicenter, single cohort study investigating the efficacy of evolocumab and nivolumab as treatment for ICI refractory mccRCC (NCT06284564). A Simon 2-stage design will be used, with 10 patients treated in the first cohort. If at least 1 objective response is observed among the first 10 patients, enrollment will continue with 19 more patients, for a total of 29 patients. Primary endpoints are objective response rates based on RECIST v1.1 as well as trial limiting toxicities for the safety profiling of the combination of treatment. Patients will be treated until progression of disease, unacceptable toxicity, or up to 2 years if ongoing response. The first stage of enrollment was completed in 2025, and the study is ongoing. The study is funded by CPRIT and open within the DOD-supported Kidney Cancer Research Consortium at UT Southwestern Simmons Comprehensive Cancer Center and MD Anderson Cancer Center. Clinical trial information: NCT06284564 .