Derazantinib alone and with atezolizumab in metastatic urothelial carcinoma with activating FGFR aberrations
Andrea Necchi, Rodryg Ramlau, Alejandro Falcón González, Arvind Chaudhry, Tilman Todenhöfer, Rana Tahbaz, Elisa Fontana, Patrizia Giannatempo, Jean-Laurent Deville, Damien Pouessel, Shinkyo Yoon, Thomas Powles, Mathieu Bernat, Manuel Häckl, Michalina Marszewska, Phil McKernan, Mikael Saulay, Federica Scaleia, Marc Engelhardt, Yohann Loriot, Arlene Siefker-Radtke, Maria De Santis- Cancer Research
- Oncology
Abstract
Background
This Phase 1 b/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% CI: 2.3, 19.6%), based on 4 partial responses. The ORR in Substudy 4 was 1/7 (14.3%, 95% CI: 0.4, 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.