Browse

A Phase 1 Study of LY2874455, an Oral Selective pan-FGFR Inhibitor, in Patients with Advanced Cancer

Cited 39 time in Web of Science Cited 37 time in Scopus
Authors
Michael, Michael; Bang, Yung-Jue; Park, Young Suk; Kang, Yoon-Koo; Kim, Tae Min; Hamid, Oday; Thornton, Donald; Tate, Sonya C.; Raddad, Eyas; Tie, Jeanne
Issue Date
2017-08
Citation
Targeted Oncology, Vol.12 No.4, pp.463-474
Abstract
Background We report here a phase 1 study of LY2874455, a potent oral selective pan-fibroblast growth factor receptor (FGFR) inhibitor. Objective The primary objective was to determine the recommended phase 2 dosing (RP2D). Secondary objectives included determining toxicity, antitumor activity, pharmacokinetics (PK), and pharmacodynamic (PD) properties of LY2874455. Patients and Methods This study comprised two parts: (a) dose escalation with 3 + 3 cohorts in patients with solid tumors and (b) dose-expansion cohorts in patients with gastric cancer (GC) and non-small cell lung cancer (NSCLC). Part A: 36 patients in 11 dose cohorts ranging from 2 to 24 mg twice daily (BID). RP2D was 16 mg BID. Part B: GC cohort, 29 patients, NSCLC cohort, 27 patients, all treated at the RP2D. Results LY2874455 was slowly absorbed and generally showed linear PK. The effective half-life was similar to 12 h. PD properties of LY2874455 occurred at doses >= 10 mg by increases in serum phosphorus. Phosphate binders were administered to control serum phosphorus. LY2874455 was generally well tolerated; most toxicities were grade 1 or 2; most frequent were hyperphosphatemia, diarrhea, and stomatitis. Efficacy: part A: 24 patients evaluable: 1 patient in the 14-mg BID cohort with GC had a partial response (PR); 14 patients had stable disease (SD); part B: NSCLC cohort: 11 of 12 evaluable patients had SD; GC cohort: 15 patients evaluable: 1 patient with PR; 12 patients with SD. Conclusions LY2874455 has an RP2D of 16 mg BID and demonstrated good tolerability and activity in solid-organ cancer patients. The role of FGFR inhibition on tumor growth in patients requires further study. (NCT01212107).
ISSN
1776-2596
URI
https://hdl.handle.net/10371/173259
DOI
https://doi.org/10.1007/s11523-017-0502-9
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse