Altered FGFR signaling is a potential target for anticancer therapy. Rogaratinib (BAY1163877) is an oral inhibitor of FGFRs 1-4. Screening for patients based on tumor FGFR1-3 mRNA overexpression, we reported in a phase I study that selected urothelial carcinoma patients were highly sensitive to rogaratinib treatment (NCT01976741; Joerger et al, ESMO 2016). Here we further identify patients sensitive to rogaratinib with malignancies not previously identified as being driven by FGFRs.
Subjects with treatment-refractory advanced or metastatic solid tumors were screened for high FGFR1-3 mRNA expression levels by RNA in situ hybridization (RNAscope®; Advanced Cell Diagnostics, Inc., Newark, CA) and Nanostring® assay (NanoString Technologies, Inc., Seattle, WA) from fresh or archival tumor specimens. FGFR-positive patients were treated with 800 mg BID on a continuous 21-day cycle. Responses were assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
More than 500 patient biopsies were screened for FGFR1-3 mRNA levels. Seventy two FGFR-positive patients were treated with rogaratinib, with 63 evaluable for response. Clinical responses were observed in tumor types not previously associated with FGFR alterations, including a partial remission (PR) in a patient with a FGFR1 mRNA-positive adenoid cystic carcinoma of the tongue and a PR in a FGFR3 mRNA-positive head and neck squamous cell carcinoma patient. Long-lasting stable disease with tumor shrinkage was also seen in patients with a) FGFR3 mRNA-positive gastric cancer, b) FGFR3 mRNA-positive lung squamous cell carcinoma c) FGFR3 mRNA-positive lung adenocarcinoma, d) FGFR2 mRNA-positive breast cancer and e) FGFR1 mRNA-positive hemangioendothelioma with complete disappearance of edema over 18 months.
Patient selection for treatment with rogaratinib based on quantification of FGFR1-3 mRNA isoforms in all tumor types irrespective of underlying data on DNA alterations is feasible and yields clinically meaningful responses in tumor types not been previously associated with altered FGFR signaling.
Clinical trial identification
Legal entity responsible for the study
S. Bender, P. Ellinghaus, M. Ocker: Employment: Bayer AG. S. Ince, P. Rajagopalan: Employment: Bayer HealthCare Pharmaceuticals. All other authors have declared no conflicts of interest.