Erdafitinib or Erdafitinib Plus Cetrelimab for Patients With Metastatic Urothelial Carcinoma and FGFR Alterations: Final Results From the Phase II NORSE Study.

Abstract

PURPOSE - First-line treatment options for cisplatin-ineligible patients with metastatic urothelial cancer (mUC) are limited. We conducted a phase II study of erdafitinib, alone or with cetrelimab, in FGFR-altered mUC.METHODS - Adults with mUC and select FGFR alterations who are ineligible for cisplatin were randomly assigned 1:1 in a noncomparative design to once-daily erdafitinib 8 mg (with pharmacodynamically guided uptitration to 9 mg) or erdafitinib 8 mg plus intravenous cetrelimab 240 mg once every 2 weeks at cycles 1-4 and 480 mg once every 4 weeks thereafter. Primary end points were investigator-assessed confirmed overall response rate (ORR) and safety; secondary end points included duration of response (DOR), progression-free survival, and overall survival (OS). No statistical hypotheses were tested.RESULTS - At data cutoff, 87 patients were randomly assigned and treated (erdafitinib, n = 43; erdafitinib plus cetrelimab, n = 44). Of 64 patients with PD-L1 expression data, 56 (87.5%) had low levels of PD-L1 expression (combined positive score =3 TRAEs occurred in 46.5% and 45.5% of patients receiving erdafitinib and erdafitinib plus cetrelimab, respectively.CONCLUSION - First-line erdafitinib monotherapy and erdafitinib plus cetrelimab demonstrated antitumor activity and a manageable safety profile in cisplatin-ineligible patients with mUC. Copyright © 2026 American Society of Clinical Oncology