507P - A phase 1 study evaluating the pharmacokinetics (PK) and safety of regorafenib (REG) in patients with advanced solid tumors with severe renal impai...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Gastrointestinal Cancers
Presenter Daniel Renouf
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors D.J. Renouf1, H.W. Hirte2, C.L. O'Bryant3, Z.J. Trnkova4, A. Cleton4, F. Huang5, U. Mueller6, J. Ayoub7, A.C. Lockhart8, D.I. Quinn9, G.K. Dy10, M.B. Sawyer11
  • 1Division Of Medical Oncology, British Columbia Cancer Agency, V5Z 1M9 - Vancouver/CA
  • 2Division Of Medical Oncology, Juravinski Cancer Centre and Escarpment Cancer Research Institute, Hamilton/CA
  • 3Department Of Clinical Pharmacy, University of Colorado Cancer Center, Aurora/US
  • 4Clinical Pharmacology Oncology, Bayer Pharma AG, Berlin/DE
  • 5Clinical Pharmacology Oncology, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 6Clinical Statistics, ClinStat GmbH, Köln/DE
  • 7Department Of Medicine, Centre Hospitalier de l'Université de Montréal, Montreal/CA
  • 8Siteman Cancer Center, Washington University School of Medicine, St. Louis/US
  • 9Norris Comprehensive Cancer Center, University of Southern California, Los Angeles/US
  • 10Department Of Medicine, Roswell Park Cancer Institute, Buffalo/US
  • 11Department Of Oncology, Cross Cancer Institute, Edmonton/CA



REG is an oral multikinase inhibitor used for the treatment of metastatic CRC and advanced GIST. This phase 1 study was designed to evaluate the PK and safety of REG in cancer patients with severe renal impairment (SRI; creatinine clearance [CLCR] ≥15 to


This was a phase 1, open-label, non-randomized, 2-parallel group study in patients with advanced solid tumors with severe vs normal/mild renal impairment (NCT01853046). REG 160 mg QD was administered as a single dose on Day 1 with a washout of ≥5 days, then as multiple doses in 28-day cycles (3 weeks on/1 week off). Antitumor activity was assessed according to RECIST v1.1 as a secondary endpoint. Blood samples were collected after single and multiple dose administration for PK analysis. Adverse events (AEs) were graded according to NCI CTCAE v4.0. Estimated CLCR was calculated using the Cockcroft–Gault equation.


24 patients (6 SRI and 18 CTR) were valid for PK and safety analyses and 21 patients for efficacy analysis. Baseline median (range) CLCR was 22.3 mL/min (22–31 mL/min) in the SRI and 82.6 mL/min (60–130 mL/min) in the CTR group. After single-dose REG, geometric mean AUC(0–tlast) was 76.6 mg × h/L in the SRI and 67.2 mg × h/L in the CTR group, whereas mean terminal half-lives were 27.9 h and 28.7 h, respectively. Inter-subject variability of AUC(0–tlast) was moderate in the 2 groups (CV 50.3% SRI and 45.5% CTR). After repeated dosing, the geometric mean AUC(0–24) for REG was 55.9 mg·h/L in the SRI and 57.5 mg·h/L in the CTR group. The most common REG-related treatment-emergent AEs were hand–foot skin reaction (54%), diarrhea (46%), fatigue (46%), nausea (42%), decreased appetite (42%), and hypertension (42%). The best response observed was stable disease in 15/21 (71%) patients.


The PK of REG 160 mg QD was not affected by severe renal impairment. No safety signal was detected for a potential influence of severe renal impairment on the safety profile of REG. No dose modification is recommended for renal impairment.

Clinical trial identification


Legal entity responsible for the study





D.J. Renouf: Research funding: Bayer. H.W. Hirte: Advisory board: AstraZeneca, Roche. C.L. O'Bryant: Advisory board: Amgen, Heron Therapeutics. Corporate-sponsored research: Bayer, Pfizer, AstraZeneca. Speakers bureau: Amgen. Z.J. Trnkova, F. Huang: Other substantive relationships: Bayer (employee). A. Cleton: Stock ownership: Bayer, AstraZeneca, Pfizer. Other substantive relationships: Bayer (employee). U. Mueller: Advisory board: Bayer. Other substantive relationships: ClinStat GmbH (employee). D.I. Quinn: Advisory boards: Bayer All other authors have declared no conflicts of interest.