193P - A phase 1 study evaluating the pharmacokinetics (PK), safety, and efficacy of regorafenib (REG) in Chinese patients with advanced, refractory solid...

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cytotoxic agents
Presenter Junning Cao
Citation Annals of Oncology (2016) 27 (suppl_9): ix53-ix67. 10.1093/annonc/mdw581
Authors J. Cao1, D. Ji1, W. Shen1, Q. Wang2, Y. Liu2, D. Lu3, I. Sturm4, F. Huang5, A. Cleton4
  • 1Department Of Medical Oncology, Fudan University Shanghai Cancer Center, 200032 - Shanghai/CN
  • 2Clinical Science, Bayer HealthCare Pharmaceuticals, 100020 - Beijing/CN
  • 3Data Sciences And Analytics, Bayer HealthCare Pharmaceuticals, 100020 - Beijing/CN
  • 4Clinical Pharmacology Oncology, Bayer AG, 13351 - Berlin/DE
  • 5Clinical Pharmacology Oncology, Bayer HealthCare Pharmaceuticals, 07981 - Whippany/US

Abstract

Background

This single-arm phase 1 study was conducted to define the PK of REG and its metabolites, M-2 and M-5, in Chinese patients with advanced solid tumors.

Methods

Patients from China mainland with locally advanced/metastatic, refractory solid tumors were enrolled if they were not candidates for standard therapy or if they had metastatic CRC or advanced GIST and REG was a treatment option. The primary objective was PK; secondary objectives were safety, tolerability, and efficacy. Single-dose PK was collected on Cycle 0 Day 1 up to 96 hours after administration of REG 160 mg followed by 6 days off treatment. From Cycle 1 Day 1, REG 160 mg was administered daily on a 3 weeks on/1 week off schedule in a 28-day cycle until tumor progression, toxicity, or withdrawal of consent. Optional multiple-dose REG PK was collected on Cycle 1 Day 21 up to 96 hours post dose where applicable.

Results

All 18 patients who received study treatment were valid for single-dose PK, safety, and efficacy analyses; 9 were valid for multiple-dose PK analysis. After single-dose REG, the geometric mean AUC(0–tlast) (mg·h/L) was 43.1 (REG), 17.1 (M-2), and 3.99 (M-5), with moderate to high inter-individual variability: Geo-CV 63% (REG), 56% (M-2), 74% (M-5). After multiple-dosing, increases in AUC(0–24) and Cmax were observed for the 3 analytes (accumulation ratios: REG, 1.83 AUC(0–24) and 1.61 Cmax; M-2, 3.44 AUC(0–24) and 3.51 Cmax; M-5, 35.8 AUC(0–24) and 21.2 Cmax). The most common drug-related grade ≥3 treatment-emergent adverse events were hypophosphatemia (39%), lipase increase (22%), and hand–foot skin reaction (22%). The best overall response was stable disease in 10/18 (56%) patients with median overall treatment duration of 9.4 weeks.

Conclusions

The inter-individual variability of REG, M-2, and M-5 was moderate to high after single- and multiple-dose REG, with observed accumulation after multiple dosing. Overall, the PK of REG, M-2, and M-5 in patients from China mainland was consistent with that previously reported. The safety profile was consistent with the known safety profile of REG. No safety signals were detected to indicate a potential influence of Chinese ethnicity on the safety profile of REG.

Clinical trial indentification

NCT02398513

Legal entity responsible for the study

Bayer

Funding

Bayer

Disclosure

Q. Wang, Y. Liu, D. Lu, F. Huang: Employee of Bayer. I. Sturm: Employee of Bayer and owns stock in Bayer. A. Cleton: Employee of Bayer and has stock in Bayer, Astrazeneca, Pfizer. All other authors have declared no conflicts of interest.