859P - Anti-tumor activity of the pan-FGFR inhibitor rogaratinib in patients with advanced urothelial carcinomas selected based on tumor FGFR mRNA express...

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Drug Development
Urothelial Cancers
Genitourinary Cancers
Presenter Martin Schuler
Citation Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371
Authors M. Schuler1, L. Nogova2, A. Heidenreich3, D. Tai4, P. Cassier5, H. Richly1, B.C. Cho6, C.M. Sayehli7, A. Navarro8, S. Bender9, M. Ocker10, H. Nogai11, A. Wagner12, S. Ince13, P. Ellinghaus9, M. Joerger14
  • 1Department Of Medical Oncology, West German Cancer Center, University Hospital Essen, 45122 - Essen/DE
  • 2Klinik I Für Innere Medizin, University Hospital Cologne, 50924 - Köln/DE
  • 3Klinik Für Urologie, University Hospital Cologne, 50937 - Köln/DE
  • 4Division Of Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 5Département D'oncologie Médicale Adulte, Centre Léon Bérard, 69008 - Lyon/FR
  • 6Department Of Internal Medicine, Yonsei Cancer Center, Seoul/KR
  • 7Early Clinical Trial Unit, University Clinic Würzburg-Medizinische Klinik und Poliklinik II Zentrum fuer Innere Medizin (ZIM), 97080 - Würzburg/DE
  • 8Deparment Of Oncology, University Hospital Vall d’Hebron, 08035 - Barcelona/ES
  • 9Biomarker Research, Bayer AG, 42113 - Wuppertal/DE
  • 10Biomarker Strategy, Bayer AG, 13353 - Berlin/DE
  • 11Clinical Pharmacology, Bayer AG, 13353 - Berlin/DE
  • 12Clinical Development, Bayer AG, 13353 - Berlin/DE
  • 13Project Management, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 14Medical Oncology & Hematology, Cantonal Hospital, 9007 - St. Gallen/CH



Fibroblast growth factor receptor (FGFR) signaling is deregulated in urothelial carcinomas (UC). Rogaratinib is an oral inhibitor of FGFRs 1-4 with demonstrated antitumor activity in bladder cancer xenograft models. We report the results from a rogaratinib phase I trial expansion cohort in UC patients selected based on FGFR1-3 mRNA tumor overexpression and/or presence of activating mutations in the FGFR3 gene.


Patients with locally advanced or metastatic UC who have progressed or ineligible for standard therapy were screened for high FGFR1-3 mRNA expression levels by RNA in situ hybridization (RNAscope®) and Nanostring® assays utilizing fresh or archival FFPE tumor specimens. FGFR3-activating mutations were evaluated by a PCR based assay (Qiagen). Patients were treated with rogaratinib 800mg BID on a continuous regimen. Tumor response was assessed by RECIST, v1.1. Adverse events were classified using CTCAE v4.03 criteria.


Biopsies from a total of 109 patients with advanced UC were screened, with 42.3% found to be FGFR positive; of which 87% due to FGFR3 mRNA overexpression, 4% FGFR1, and 9% mixed FGFR isoform mRNA expression. Co-ocurrence of FGFR3-activating mutations and high FGFR3 mRNA expression was seen in 8% of patients. Among 20 patients with UC treated with rogaratinib, 16 (75%) had tumor shrinkage in target lesions with 9 (45%) showing tumor shrinkage of more than 20%, and 6 (30%) having a partial response (PR). Disease control rate (CR+PR+SD>12w) was 75%. Three patients with a PR had elevated tumor FGFR3 mRNA levels without corresponding genomic alterations. The most frequent AEs were hyperphosphatemia and diarrhea.


Selection of UC patients for treatment with rogaratinib based on FGFR1-3 mRNA expression levels in archival tissue was feasible and identified patients benefitting from treatment without having aberrations of FGFR-encoding genes. Rogaratinib has a favorable safety profile and showed anti-tumor activity in biomarker-selected UC patients which warrants further clinical development.

Clinical trial identification


Legal entity responsible for the study

Bayer AG


Bayer AG


M. Schuler: Consultant: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, Novartis, Roche; Honoraria: Alexion, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, Novartis Research: Boehringer Ingelheim, Bristol Myers-Squibb, Novar. S. Bender, M. Ocker, H. Nogai, A. Wagner, P. Ellinghaus: Employment: Bayer AG. S. Ince: Employment: Bayer HealthCare Pharmaceuticals. All other authors have declared no conflicts of interest.