ENERGIZE: a Phase III study of neoadjuvant chemotherapy alone or with nivolumab with/without linrodostat mesylate for muscle-invasive bladder cancer
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, 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
Abstract
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.
Source: PubMed