Immune checkpoint inhibitors have revolutionized the treatment of patients with metastatic urothelial carcinoma. In cisplatin-eligible muscle-invasive bladder cancer (MIBC), cisplatin-based neoadjuvant chemotherapy (NAC) before radical cystectomy improves overall survival. Tumor PD-L1 expression increases in MIBC after NAC, suggesting potential synergy in combining PD1/PD-L1 inhibitors with NAC. IDO1 is overexpressed in bladder cancer and is associated with poor outcomes. Linrodostat mesylate (BMS-986205) - a selective, potent, oral IDO1 inhibitor - combined with nivolumab has demonstrated safety and preliminary evidence of clinical activity in metastatic urothelial carcinoma. Here, we discuss the rationale and trial design of the ENERGIZE, a Phase III trial investigating the efficacy of NAC in combination with nivolumab with or without linrodostat followed by postsurgery nivolumab or nivolumab with linrodostat in cisplatin-eligible patients with MIBC. Clinical trial registration number: NCT03661320.
Future oncology (London, England). 2019 Dec 11 [Epub ahead of print]
Guru Sonpavde, Andrea Necchi, Shilpa Gupta, Gary D Steinberg, Juergen E Gschwend, Michiel Simon Van Der Heijden, Nathalie Garzon, Mohammed Ibrahim, Bradley Raybold, Danny Liaw, Mark Rutstein, Matt D Galsky
Dana-Farber Cancer Institute, Genitourinary Oncology Division, Boston, MA 02215, USA., Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Department of Medicine, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA., Department of Urology NYU Langone Health, New York University, New York, NY 10017, USA., Department of Urology, Technical University of Munich, Munich, Germany., Department of Medical Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands., Bristol-Myers Squibb, Princeton, NJ 08540, USA., Department of Medicine, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY 10029, USA.