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Derazantinib alone and with atezolizumab in metastatic urothelial carcinoma with activating FGFR aberrations

Background: This Phase 1b/2 study assessed the efficacy in terms of objective response rate (ORR) of the FGFR1/2/3 kinase inhibitor derazantinib as monotherapy or in combination with atezolizumab in patients with metastatic urothelial cancer (mUC) and FGFR1-3 genetic aberrations (FGFR1-3GA).

Methods: This multicenter, open-label study comprised 5 substudies. In Substudies 1 and 5, patients with mUC with FGFR1-3GA received derazantinib monotherapy (300 mg QD in Substudy 1, 200 mg BID in Substudy 5). In Substudy 2, patients with any solid tumor received atezolizumab 1200 mg every 3 weeks plus derazantinib 200 or 300 mg QD. In Substudy 3, patients with mUC harboring FGFR1-3GA received derazantinib 200 mg BID plus atezolizumab 1200 mg every 3 weeks. In Substudy 4, patients with FGFR inhibitor-resistant mUC harboring FGFR1-3GA received derazantinib 300 mg QD monotherapy or derazantinib 300 mg QD plus atezolizumab 1200 mg every 3 weeks.

Results: The ORR for Substudies 1 and 5 combined was 4/49 (8.2%, 95% confidence interval = 2.3% to 19.6%), which was based on 4 partial responses. The ORR in Substudy 4 was 1/7 (14.3%, 95% confidence interval = 0.4% to 57.9%; 1 partial response for derazantinib 300 mg monotherapy, zero for derazantinib 300 mg plus atezolizumab 1200 mg). In Substudy 2, derazantinib 300 mg plus atezolizumab 1200 mg was identified as a recommended dose for Phase 2. Only 2 patients entered Substudy 3.

Conclusions: Derazantinib as monotherapy or in combination with atezolizumab was well-tolerated but did not show sufficient efficacy to warrant further development in mUC. Clinicaltrials.gov NCT04045613, EudraCT 2019-000359-15.

Andrea Necchi,1,2 Rodryg Ramlau,3 Alejandro Falcón González,4 Arvind Chaudhry,5 Tilman Todenhöfer,6 Rana Tahbaz,7 Elisa Fontana,8 Patrizia Giannatempo,9 Jean-Laurent Deville,10 Damien Pouessel,11 Shinkyo Yoon,12 Thomas Powles,13 Mathieu Bernat,14 Manuel Häckl,14 Michalina Marszewska,14 Phil McKernan,14 Mikael Saulay,14 Federica Scaleia,14 Marc Engelhardt,14 Yohann Loriot,15 Arlene Siefker-Radtke,16 Maria De Santis7,17

  1. Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy.
  2. Vita-Salute San Raffaele University, Milan, Italy.
  3. Oncology Department, Poznań University of Medical Sciences, Poznań, Poland.
  4. Department of Medical Oncology, Hospital Universitario Virgen Del Rocio, Sevilla, Spain.
  5. Medical Oncology Associates, Summit Cancer Centers, Spokane, WA, USA.
  6. Studienpraxis Urologie, Nürtingen, Germany.
  7. Department of Urology, Charité Universitätsmedizin Berlin, Berlin, Germany.
  8. Sarah Cannon Research Institute, London, UK.
  9. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  10. Fédération de Cancérologie, CHU Timone, Marseille, France.
  11. Department of Medical Oncology and Clinical Research Unit, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse (IUCT-Oncopôle), Toulouse, France.
  12. Department of Oncology, Asan Medical Center, Seoul, Republic of Korea.
  13. Barts Cancer Centre, Barts Health NHS Trust, London, UK.
  14. Basilea Pharmaceutica International Ltd, Allschwil, Switzerland.
  15. Medical Oncology Department, Institut Gustave Roussy, Villejuif, France.
  16. The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  17. Department of Urology, Medical University of Vienna, Vienna, Austria.
Source: Andrea Necchi, Rodryg Ramlau, Alejandro Falcón González et al. Derazantinib alone and with atezolizumab in metastatic urothelial carcinoma with activating FGFR aberrations. JNCI Cancer Spectr. 2024 Apr 30;8(3):pkae030. doi: 10.1093/jncics/pkae030.

Read an Expert Commentary by Bishoy Faltas, MD