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

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.

• Authors: 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
• Journal: Future oncology (London, England) (Future Oncol) Vol. 16 Issue 2 Pg. 4359-4368 (Jan 2020) ISSN: 1744-8301 [Electronic] England
• PMID: 31823654 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Acetamides
• Biomarkers, Tumor
• Quinolines
• linrodostat
• Nivolumab
• Cisplatin

Topics

• Acetamides (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (metabolism)
• Cisplatin (administration & dosage)
• Double-Blind Method
• Humans
• Muscle Neoplasms (drug therapy, pathology)
• Neoadjuvant Therapy
• Neoplasm Invasiveness
• Nivolumab (administration & dosage)
• Prognosis
• Quinolines (administration & dosage)
• Survival Rate
• Urinary Bladder Neoplasms (drug therapy, metabolism, pathology)