A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer

Janssen Research & Development, LLC
Study Design: 
Patients with metastatic urothelial cancer with select FGFR alterations, measurable disease, no prior systemic therapy, and who were ineligible to receive cisplatin were enrolled. Any PD-(L)-1 status could be enrolled. Patients were randomized to either erdafitinib alone or erdafitinib and cetrelimab.
Currently, first-line therapy for cisplatin-ineligible patients with metastatic urothelial cancer is alternative chemotherapy or anti-PD-(L)-1 monotherapy. The pan-fibroblast growth factor receptor (FGFR) inhibitor, erdafitinib, is indicated as second-line therapy in metastatic urothelial cancer with targetable FGFR alterations. The phase Ib trial determined a tolerable dose of erdafitinib and the anti-PD-1 antibody, cetrelimab, as a second-line regimen in metastatic patients. The phase II part of the trial is reported here which evaluates erdafitinib alone or erdafitinib and cetrelimab as a first-line regimen in cisplatin-ineligible patients with FGFR alterations.
The primary endpoints were overall response rate (ORR) per RECIST 1.1 and safety. Secondary endpoints included disease control rate, time to response, and duration of response.
The results demonstrate activity with the combination of erdafitinib and cetrelimab in first line, cisplatin-ineligible patients with metastatic urothelial cancer with FGFR alterations. These alterations are more frequent in upper tract tumors than in bladder cancer. Although of interest, other very promising regimens for first line, cisplatin-ineligible patients currently exist (such as enfortumab vedotin and pembrolizumab).
The reported results of the Norse Trial at ESMO 2021 were as of July 2021. As of that date, 53 patients were randomized but ORR was evaluable in 37 patients. The ORR was 33% in the erdafitinib arm vs. 68% in the combination arm. The complete response rate was 6% vs. 21%, respectively. The median duration of response was not evaluable in the erdafitinib arm and 6.9 months in the combination arm. The safety data included 48 total patients with the side effects being attributable to the ertafinitib including hyperphosphatemia (58% erdafitinib vs. 58% combination), stomatitis (63% vs. 54%, respectively), and diarrhea (50% vs. 42%, respectively).