380P - A phase 1b study evaluating the safety and pharmacokinetics (PK) of regorafenib (REG) in combination with cetuximab (CTX) in patients with advanced...

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cytotoxic agents
Clinical research
Basic Scientific Principles
Biological therapy
Presenter Colin Weekes
Citation Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367
Authors C. Weekes1, A.C. Lockhart2, H. Lenz3, J.J. Lee4, A. Cleton5, F. Huang6, I. Sturm7
  • 1Division Of Hematology/oncology, Massachusetts General Hospital, 02114 - Boston/US
  • 2Department Of Medicine, University of Miami, 33146 - Coral Gables/US
  • 3Division Of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, 90089-9173 - Los Angeles/US
  • 4Division Of Hematology-oncology, Department Of Medicine, University of Pittsburgh School of Medicine, 15261 - Pittsburgh/US
  • 5Clinical Pharmacology Oncology, Bayer AG, 13353 - Berlin/DE
  • 6Clinical Pharmacology Oncology, Bayer HealthCare Pharmaceuticals, 07981 - Whippany/US
  • 7Translational Medicine Oncology, Bayer AG, 13353 - Berlin/DE



Combining REG with CTX may overcome intrinsic and acquired resistance in EGFR-sensitive and -resistant tumors. We evaluated the safety, PK, maximum tolerated dose (MTD), and preliminary efficacy of REG plus standard dose of CTX (initial 400 mg/m2 intravenously followed by 250 mg/m2 weekly) in a phase 1b study. Final results from the intermittent REG dosing arm (3 weeks on/1 week off) are reported, with final results from the terminated continuous REG dosing arm (n = 11) previously presented (Weekes et al. AACR 2016, abstract CT148).


This was an open-label, dose-escalation (3 + 3 design) study in patients with locally advanced or metastatic solid tumors who progressed after standard therapy. The starting dose of REG was 120 mg once daily (QD) in a 28-day cycle (3 weeks on/1 week off) plus CTX. If tolerable, REG was escalated to 160 mg QD. If not tolerable, the REG dose was reduced to 80 mg QD. Dose-limiting toxicities (DLTs) were evaluated in Cycle 1. Adverse events (AEs) were graded according to NCI-CTCAE v4.03. Antitumor activity was assessed using RECIST v1.1.


As of January 31, 2017, 31 patients received REG in an intermittent schedule plus CTX: 8 patients received REG 120 mg and 23 received REG 160 mg. One DLT of grade 3 hand–foot skin reaction was reported in 6 evaluable patients at the 120 mg dose level. No DLT was confirmed at the 160 mg dose level. The MTD was declared at the standard dose of REG 160 mg QD (3 weeks on/1 week off) plus the standard dose of CTX. The most common AEs, regardless of relationship to study drug, were hypophosphatemia (42%), fatigue (39%), and nausea (39%). The most common grade ≥3 REG-related AEs were hypophosphatemia (23%) and fatigue (10%). REG AUC(0–tlast) was 29.1 mg·h/L at 160 mg and 17.4 mg·h/L at 120 mg. CTX had no effect on the PK of REG. One patient (120 mg REG) had a partial response; 6 (160 mg REG; 29%) and 2 (120 mg REG; 25%) patients had stable disease.


REG at 160 mg QD (3 weeks on/1 week off) plus standard dose of CTX was tolerated with no unexpected toxicities. Observed AEs were in line with known REG and CTX safety profiles.

Clinical trial identification


Legal entity responsible for the study





C. Weekes: Advisory Board: Celgene, Merrimack, Bayer. A.C. Lockhart: Corporate Sponsored Research: Amgen, Bayer, Daiichi Sankyo, EMD Serono, Genentech/Roche, Eli Lilly, Millennium/Takeda, Novartis, Sanofi, Teva, Zenyaku Kogyo. H-J. Lenz: Research/Education Grant, Honoraria, Advisory Board and Consulting: Bayer, EMD. J.J. Lee: Research/Education Grant: Merck Advisory Board: Genentech/Roche. A. Cleton: Employment: Bayer. Stock Ownership: Bayer, Pfizer. F. Huang, I. Sturm: Employment and Stock Ownership: Bayer.