Although first-line cisplatin-based chemotherapy prolongs survival in advanced urothelial cancer (UC), most patients (pts) progress within 8 months and no standard second-line therapies are currently available. Recent studies with anti-PD-L1 agents in pretreated UC have shown antitumour activity and promising survival compared with historical controls. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody that has shown an acceptable safety profile and clinical activity across a range of tumour types in a large phase 1b study. In an expansion cohort of pts with pretreated UC, treatment with avelumab resulted in a 16% objective response and 59% disease control rate. A phase 3 study (NCT02603432) has been initiated to determine if maintenance therapy with avelumab can prolong the benefit of first-line chemotherapy in pts with advanced UC.
JAVELIN Bladder 100 is a phase 3, international, open-label trial of avelumab + best supportive care (BSC) compared with BSC alone administered as maintenance treatment for pts with locally advanced/metastatic UC whose disease did not progress after first-line treatment with 4–6 cycles of gemcitabine + cisplatin or gemcitabine + carboplatin. Other eligibility criteria include measurable disease prior to chemotherapy and adequate hematologic/organ function. Avelumab 10 mg/kg is administered every 2 wks as a 1 hr infusion. An estimated 668 pts will be randomized 1:1 and stratified based on best response to first-line chemotherapy and metastatic site. This trial has 2 co-primary populations: pts with PD-L1–positive tumours and all pts. The primary endpoint is overall survival and secondary endpoints include progression-free survival (PFS), objective response, safety, and symptoms/quality of life. Tumour response and PFS (RECIST v1.1) are assessed by blinded central review. Trial enrolment began in May 2016. *Proposed INN.
Clinical trial identification
Legal entity responsible for the study
T. Powles: Research Funding: AZ and Roche Honoraria: Novartis, BMS, Merck. P. Grivas: Consulting/Advisory/Honoraria: Genentech, Deudreon, Bayer Speaker Bureau: Genentech. Research Funding: Pfizer, Merck, Oncogenex, Mirati, Roche, Bayer. J.B. Aragon-Ching: Honoraria/Consulting/Advisory: AZ, Algeta/Bayer, Dendreon Speakers Bureau: BMS. Y. Faroun: Honoraria: Celgene Speakers' Bureau: BMS, Celgene Travel/Accommodations/Expenses: Celgene. Y. Tomita: Consulting/Advisory Role: Novartis Research funding: Pfizer, Astellas, AZ. D. Chakrabarti: Employee and stockholder: Pfizer Inc. R.J. Laliberte: Employee: Pfizer Inc, Galena Biopharma, Inc. M. Shnaidman: Employee: Merck KGaA. All other authors have declared no conflicts of interest.