PD-(L)1 inhibitors have been shown to be effective in patients with metastatic urothelial cancer (UC) who are ineligible to receive cisplatin-based chemotherapy, with the PD-L1 inhibitor atezolizumab being FDA-approved. Dysregulation of fibroblast growth factor receptors (FGFR) has been shown to play a role in UC development and progression, and FGFR3 overexpression/molecular alterations are associated with a non-T-cell inflamed tumor microenvironment. Rogaratinib, an oral pan-FGFR 1-4 inhibitor, has shown promising efficacy in a phase I study in UC patients selected based on FGFR1-3 overexpression, including patients who rapidly progressed on immunotherapy. The aim of this study is to explore the clinical safety and benefit of combining rogaratinib with atezolizumab.
This is a multicenter, phase 1b/2 study of rogaratinib in combination with atezolizumab in patients with FGFR-positive locally advanced or metastatic UC. The primary objectives of the single-arm phase 1b portion are to determine the safety, tolerability, recommended phase-2 dose (RP2D) and pharmacokinetics of rogaratinib in combination with atezolizumab. The primary objective of the randomized phase 2 portion is to compare progression-free survival (PFS) of rogaratinib plus atezolizumab versus placebo plus atezolizumab in chemotherapy-untreated patients with FGFR-positive locally advanced or metastatic UC. Patients will be tested for FGFR1/3 mRNA expression levels in archival tumor samples (RNAscope®) and patients with FGFR-positive UC will enter into screening, regardless of the presence of FGFR mutations or translocations. Eligible patients will be treated with a starting dose of daily rogaratinib 800 mg po bid together with a fixed dose of 1200 mg atezolizumab iv on day 1 of a 21-day cycle. Following determination of the RP2D, patients will be randomized 1:1 to rogaratinib plus atezolizumab versus placebo plus atezolizumab. The primary efficacy variable is PFS based on assessment of blinded independent central review. Approximately 160 patients will be enrolled.
Clinical trial identification
Legal entity responsible for the study
K. Nakajima, C. Lu, H. Nogai: Employee: Bayer. All other authors have declared no conflicts of interest.