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

TPS612 Background: While metastatic renal cell carcinoma (mRCC) is known to be immunogenic, and there have been several recent advances with combinations of immunotherapy, the disease often progresses and immunotherapy resistance mechanisms remain unclear. For patients with mRCC refractory to immunotherapy checkpoint inhibitors (ICIs), further treatment options are not curative and improvements are needed. Proprotein convertase subtilisin/kexin type 9 (PCSK9) directs MHC-I molecules to the lysosome, and inhibition of PCSK9 improves MHC-I expression and tumor antigen presentation. Evolocumab is a PCSK9 inhibitor which was shown in preclinical studies to improve tumor antigen presentation, intratumoral CD8 T-cell infiltration (and activation), and overall tumor control. We designed a phase 2 trial with safety lead in adding evolocumab to the PD-1 inhibitor nivolumab in mRCC refractory to first-line ICI combinations. Methods: BOOST-RCC is an investigator-initiated, phase 2, multicenter, single cohort study investigating the efficacy of evolocumab and nivolumab for ICI refractory mRCC. 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 study is funded by CPRIT and open within the DOD-supported Kidney Cancer Research Consortium. Enrollment is ongoing at UT Southwestern Simmons Comprehensive Cancer Center and MD Anderson Cancer Center (NCT06284564). Clinical trial information: NCT06284564 .