ESMO 2021: Erdafitinib or Erdafitinib Plus Cetrelimab for Patients with Metastatic or Locally Advanced Urothelial Carcinoma and Fibroblast Growth Factor Receptor Alterations: First Phase 2 Results From the NORSE Study

( The European Society of Medical Oncology (ESMO) 2021 annual meeting’s non-prostate cancer preferred paper session included a presentation by Dr. Thomas Powles discussing the first phase 2 results from the NORSE study assessing erdafitinib or erdafitinib plus cetrelimab for patients with metastatic or locally advanced urothelial carcinoma and fibroblast growth factor receptor (FGFR) alterations. First-line therapy for cisplatin-ineligible patients with metastatic urothelial carcinoma includes alternative chemotherapy or anti-PD-(L)1 monotherapy for PD-L1 positive tumors. Given that >50% of patients with metastatic urothelial carcinoma are ineligible for cisplatin treatment, there is a significant unmet need for new treatments for these particular patients.

The pan-FGFR inhibitor erdafitinib has established clinical benefit in second-line metastatic urothelial carcinoma for patients with targetable FGFR alterations. Neoantigen release by erdafitinib may prime the tumor microenvironment for response, and erdafitinib combined with the anti-PD-1 cetrelimab could expand first-line options for patients with FGFR alterations. Importantly, the phase 1b part of NORSE (NCT03473743) determined a tolerable dose of erdafitinib + cetrelimab in patients with second-line metastatic urothelial carcinoma. At the 2021 ESMO meeting, Dr. Powles and colleagues reported early results from the phase 2 part of NORSE evaluating erdafitinib or erdafitinib + cetrelimab in cisplatin-ineligible patients with first-line metastatic urothelial carcinoma and FGFR alterations.

The NORSE phase 2 trial is enrolling patients ≥ 18 y with metastatic urothelial carcinoma, select FGFR alterations (mutation/fusion), and measurable disease (no prior systemic therapy for metastatic urothelial carcinoma, cisplatin-ineligible). Patients are randomized 1:1 to receive once-daily erdafitinib 8 mg (with pharmacodynamically guided up-titration to 9 mg) or erdafitinib 8 mg (no up-titration) + IV cetrelimab 240 mg every 2 weeks at cycles 1-4 and 480 mg every 4 weeks thereafter. Primary endpoints are investigator-assessed overall response rate (ORR) per RECIST 1.1 and safety. Secondary include disease control rate (DCR), time to response (TTR), and duration of response (DOR). The study design for the NORSE study is as follows:


As of July 19, 2021, 53 patients were randomized, including 26 to erdafitinib and 27 to erdafitinib + cetrelimab. For erdafitinib versus erdafitinib + cetrelimab, the median age was 75 versus 69 years, visceral metastases were present in 54% versus 52%, and ECOG was 0-1 in 77% versus 63%. Efficacy data in response-evaluable patients showed an ORR of 68% for erdafitinib + cetrelimab versus 33% for erdafitinib alone. The complete efficacy data is as follows:


Patients in both treatment arms had a durable reduction in the sum of their target lesion diameters over time, with a median maximum reduction in the sum of target lesion diameters of 28% in the erdafitinib arm and 51% in the erdafitinib + cetrelimab arm: 


The safety set comprised 24 patients who received erdafitinib and 24 who received erdafitinib + cetrelimab. The most frequent treatment-emergent adverse events were hyperphosphatemia (erdafitinib versus erdafitinib + cetrelimab: 58% vs 58%), stomatitis (63% versus 54%), and diarrhea (50% versus 42%). 

Dr. Powles concluded his presentation of the first results of the phase 2 NORSE study with the following take-home messages:

  • These are the first data on erdafitinib + cetrelimab in patients with newly diagnosed metastatic urothelial carcinoma with FGFR alterations who were ineligible for cisplatin-based therapy
  • Preliminary findings suggest that adding cetrelimab to erdafitinib may improve ORR and depth of response in this population
  • Clinical activity was observed in both patients with PD-L1 high and low status, however, the PD-L1 status was not known for all patients at the time of analysis for this ongoing study
  • Overall safety with erdafitinib + cetrelimab was generally consistent with erdafitinib alone and aligned with the known safety profile of approved anti-PD-1 therapies, however, discontinuation of >=1 therapy occurred more frequently in the erdafitinib + cetrelimab arm than in the erdafitinib monotherapy arm
  • These data suggest potential interaction between erdafitinib and cetrelimab, possibly mediated by priming the immune environment via neoantigen release in patients with FGFR alterations to increase response to immune checkpoint blockade
  • Enrollment in NORSE is ongoing and supported by these data


Presented by: Thomas Powles, MBBS, MRCP, MD, Department of Genitourinary Oncology, Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St. Bartholomew's Hospital, London, UK

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.