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Developmental therapeutics

3198 - Phase I study of the pan-fibroblast growth factor receptor (FGFR) inhibitor BAY 1163877 with expansion cohorts for subjects based on tumor FGFR mRNA expression levels


08 Oct 2016


Developmental therapeutics


Markus Joerger


Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435


M. Joerger1, R. Soo2, B.C. Cho3, A. Navarro Mendivil4, C. Sayehli5, H. Richly6, D. Tai7, D. Kim8, J. Wolf9, P. Cassier10, P. Ellinghaus11, S. Hildebrandt12, S. Behre13, C. Helmbrecht13, S. Kerpen13, D. Zielinski14, S. Ince15, P. Rajagopalan16, M. Ocker17, M. Schuler18

Author affiliations

  • 1 Dept. Of Oncology, Cantonal Hospital, 9007 - St. Gallen/CH
  • 2 Cancer Institute, National University Cancer Institute, Singapore, Singapore/SG
  • 3 Internal Medicine, Yonsei Cancer Center, Seoul/KR
  • 4 Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 5 Medical Oncology, University Hospital Wuerzburg, Würzburg/DE
  • 6 West German Cancer Center, University Hospital Essen, Essen/DE
  • 7 Dept. Medical Oncology, National Cancer Center, 169610 - Singapore/SG
  • 8 Department Of Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 9 Internal Medicine, University Hospital of Cologne, Cologne/DE
  • 10 Medical Oncology, Léon Bérard Cancer Center, Lyon/FR
  • 11 Biomarker Research, Bayer AG, Berlin/DE
  • 12 Clinical Development, Bayer AG, Berlin/DE
  • 13 Clinical Development, Linical Europe GmbH, Frankfurt am Main/DE
  • 14 Molecular Pathology, Targos GmbH, Kassel/DE
  • 15 Clinical Development, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 16 Clinical Pharmacology, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 17 Clinical Sciences, Bayer AG, Berlin/DE
  • 18 Medical Oncology, University Hospital Essen, Essen/DE


Abstract 3198


FGFRs are potential targets for anticancer therapy. Because FGFR expression can be de-regulated by genetic and epigenetic mechanisms, tumor FGFR mRNA levels may identify patients likely to benefit from FGFR-targeted approaches. BAY 1163877 (BAY) is an oral, potent small molecule inhibitor of FGFRs 1-3. We conducted a first-in-human dose-escalation (DE) study of BAY in subjects with advanced solid tumors, followed by expansion cohorts (ECs) in selected subjects with high tumor FGFR1-3 mRNA levels (NCT01976741).


Subjects with treatment-refractory advanced or metastatic solid tumors were enrolled in 6 dose cohorts ranging from 50-800 mg BID on a continuous 21-day cycle. Pharmacokinetics (PK) were evaluated on days 1 and 15 of cycle 1. Subjects were enrolled to 3 ECs (non-small cell lung cancer [NSCLC], bladder cancer and head and neck squamous cell carcinoma [HNSCC], and all-comers) based on high FGFR expression levels by RNAscope™ and Nanostring™ analysis of fresh or archival tumor specimens. Objective responses were assessed by RECIST 1.1 after cycle 2.


Seventy-six patients with advanced solid tumors were enrolled and treated, including 23 patients in the DE phase and 53 patients in the ECs. BAY was absorbed rapidly and exhibited an average plasma half-life of 12.7 hours. The most common adverse events were hyperphosphatemia, diarrhea and alopecia (grade 1 and 2). We observed a less than dose-proportional increase in exposure at doses > 200 mg BID, and based on effective target inhibition and a lack of dose-limiting toxicities 800 mg BID was declared as the recommended phase-2 dose. From 44 evaluable patients, 5 partial responses (PR) were seen from patients in the ECs, including HNSCC, sqNSCLC, adenoidcystic carcinoma of the tongue, and 2 with bladder cancer. An additional 18 EC patients had stable disease (SD) >12 weeks, of whom 8 had SD >24 weeks. The majority of patients, including 4 of 5 with PR, did not have FGFR genetic alterations.


BAY 1163877 at doses up to 800 mg BID was safe and well tolerated. The response profile supports selection of patients for treatment with a FGFR inhibitor based on tumor FGFR mRNA levels.

Clinical trial identification


Legal entity responsible for the study

Bayer AG


Bayer AG


R. Soo: Honoraria: Astra-Zeneca, Boehringer Ingelheim, Lilly, Merck, Novartis, Pfizer, Roche, Taiho Consulting/advisory: Astra-Zeneca, Boehringer Ingelheim, Merck, Novartis, Pfizer, Roche, Taiho. P. Ellinghaus, S. Hildebrandt, M. Ocker: Employee of Bayer AG. S. Behre, C. Helmbrecht, S. Kerpen: Employee of Linical Europe GmbH. D. Zielinski: Employee of Targos GmbH. S. Ince, P. Rajagopalan: Employee of Bayer HealthCare Pharmaceuticals. M. Schuler: Research: Boehringer-Ingelheim, BMS, Novartis Honoraria/consultancies: Alexion, AZ, BI, BMS, Celgene, IQWig, GSK, Lilly, Novartis, Pfizer. All other authors have declared no conflicts of interest.

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