A phase II study bolstering outcomes by optimizing immunotherapy strategies with evolocumab and nivolumab in patients with metastatic renal cell carcinoma (BOOST-RCC).
Abstract
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 .
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Tian Zhang
Division of Hematology‐Oncology, Department of Internal Medicine University of Texas Southwestern Medical Center Dallas Texas USA
Rebecca Slack Tidwell
Song Zhang
Qian Qin
Suzanne Cole
From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) — all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana–Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) — both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) — both in...
Pavlos Msaouel
Andrew Warren Hahn
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Amishi Yogesh Shah
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Matthew T. Campbell
Changchuan Jiang
Joseph Vento
Department of Internal Medicine, Division of Hematology and Oncology, UT Southwestern, Dallas, TX
Kevin Dale Courtney
Department of Internal Medicine, Division of Hematology and Oncology, UT Southwestern, Dallas, TX
James Brugarolas
Lauren Michelle Wood
The University of Texas MD Anderson Cancer Center, Houston, TX
Wadih Issa
Department of Internal Medicine, Division of Hematology/Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX
Navneet Kaur
Andrew Zhuang Wang
Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX
Nizar M. Tannir
Hans J. Hammers
UT Southwestern Medical Center, Dallas, TX
Eric Jonasch
Department of Genitourinary Medical Oncology The University of Texas MD Anderson Cancer Center Houston Texas USA